Angelman syndrome: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
No edit summary
 
(3 intermediate revisions by the same user not shown)
Line 16: Line 16:


==Overview==
==Overview==
Angelman syndrome, formerly known as "happy puppet syndrome", is a [[genetic disorder]] characterized by [[Cognitive delay|intelectual]] and [[development delay]], [[Seizure|seizures]], [[puppet-like movement]], unprovoked [[laughter]]/[[Smile|smiling]], and excessive [[socialization]] with strangers.<ref name=":0">{{Cite book|title=Deletion Syndromes/ Step up to USMLE step 2CK|last=Jenkins|first=Brian|publisher=Wolters Kluwer|year=2016|isbn=978-1496309747|location=Fort Worth, Texas|pages=291}}</ref>
Angelman syndrome, formerly known as "happy puppet syndrome", is a [[genetic disorder]] characterized by [[Cognitive delay|intelectual]] and [[development delay]], [[Seizure|seizures]], [[puppet-like movement]], unprovoked [[laughter]]/[[Smile|smiling]], and excessive [[socialization]] with strangers.


<br />
<br />
==Historical Perspective==
==Historical Perspective==


* Angelman syndrome was first [[discovered]] by [[Dr. Harry Angelman]], a British [[Pediatricians|pediatrician]], in 1965 during his seminar, where he described three children with the typical [[facies]] of the [[syndrome]].<ref name="doctor">{{WhoNamedIt|synd|225|Angelman's syndrome}}</ref><ref name="Angelman2008">{{cite journal|last1=Angelman|first1=Harry|title=‘Puppet’ Children A Report on Three Cases|journal=Developmental Medicine & Child Neurology|volume=7|issue=6|year=2008|pages=681–688|issn=00121622|doi=10.1111/j.1469-8749.1965.tb07844.x}}</ref>
*Angelman syndrome was first [[discovered]] by [[Dr. Harry Angelman]], a British [[Pediatricians|pediatrician]], in 1965 during his seminar, where he described three children with the typical [[facies]] of the [[syndrome]].<ref name="doctor">{{WhoNamedIt|synd|225|Angelman's syndrome}}</ref><ref name="Angelman2008">{{cite journal|last1=Angelman|first1=Harry|title=‘Puppet’ Children A Report on Three Cases|journal=Developmental Medicine & Child Neurology|volume=7|issue=6|year=2008|pages=681–688|issn=00121622|doi=10.1111/j.1469-8749.1965.tb07844.x}}</ref>
* In 1965,Dr. Angelman quoted in his seminal paper:
*In 1965,Dr. Angelman quoted in his seminal paper:


''"I happened to see an oil painting...called... "a Boy with a Puppet". The boy's laughing face and the fact that my patients exhibited jerky movements gave me the idea of writing an article about the three children with a title of Puppet Children."''<ref name="doctor" />
''"I happened to see an oil painting...called... "a Boy with a Puppet". The boy's laughing face and the fact that my patients exhibited jerky movements gave me the idea of writing an article about the three children with a title of Puppet Children."''<ref name="doctor" />


* In 1987, maternal [[allele]] [[Deletion (genetics)|deletion]] in [[chromosome 15]] was first identified in the [[pathogenesis]] of Angelman syndrome.<ref name="pmid22830052">{{cite journal |vauthors=Jana NR |title=Understanding the pathogenesis of Angelman syndrome through animal models |journal=Neural Plast. |volume=2012 |issue= |pages=710943 |date=2012 |pmid=22830052 |pmc=3399338 |doi=10.1155/2012/710943 |url=}}</ref>
*In 1987, maternal [[allele]] [[Deletion (genetics)|deletion]] in [[chromosome 15]] was first identified in the [[pathogenesis]] of Angelman syndrome.<ref name="pmid22830052">{{cite journal |vauthors=Jana NR |title=Understanding the pathogenesis of Angelman syndrome through animal models |journal=Neural Plast. |volume=2012 |issue= |pages=710943 |date=2012 |pmid=22830052 |pmc=3399338 |doi=10.1155/2012/710943 |url=}}</ref>
* In 1994 [[Point mutation|point mutations]] in ''UBE3A'' [[gene]] was known to be the [[gene]] responsible for Angelman syndrome.<ref name="pmid22830052" /><ref name="pmid9585605">{{cite journal |vauthors=Malzac P, Webber H, Moncla A, Graham JM, Kukolich M, Williams C, Pagon RA, Ramsdell LA, Kishino T, Wagstaff J |title=Mutation analysis of UBE3A in Angelman syndrome patients |journal=Am. J. Hum. Genet. |volume=62 |issue=6 |pages=1353–60 |date=June 1998 |pmid=9585605 |pmc=1377156 |doi=10.1086/301877 |url=}}</ref>
*In 1994 [[Point mutation|point mutations]] in ''UBE3A'' [[gene]] was known to be the [[gene]] responsible for Angelman syndrome.<ref name="pmid22830052" /><ref name="pmid9585605">{{cite journal |vauthors=Malzac P, Webber H, Moncla A, Graham JM, Kukolich M, Williams C, Pagon RA, Ramsdell LA, Kishino T, Wagstaff J |title=Mutation analysis of UBE3A in Angelman syndrome patients |journal=Am. J. Hum. Genet. |volume=62 |issue=6 |pages=1353–60 |date=June 1998 |pmid=9585605 |pmc=1377156 |doi=10.1086/301877 |url=}}</ref>


<br />
==Pathophysiology==
==Pathophysiology==


=== Modes of Inheritance ===
===Modes of Inheritance===


* In 70% of the cases, Angelman syndrome is caused by a sporadic (de novo) maternal [[Deletion (genetics)|deletion]] in [[Chromosome abnormality|chromosomal]] region [[:File:Angelman.PNG|15q11-13]] causing an absence of [[UBE3A gene|''UBE3A'' gene]], involving the [[Ubiquitin-protein ligase|ubiquitin pathway]].<ref name="Clayton-SmithPembrey1992">{{cite journal|last1=Clayton-Smith|first1=J|last2=Pembrey|first2=M E|title=Angelman syndrome.|journal=Journal of Medical Genetics|volume=29|issue=6|year=1992|pages=412–415|issn=1468-6244|doi=10.1136/jmg.29.6.412}}</ref>
*In 70% of the cases, Angelman syndrome is caused by a sporadic (''de novo'') maternal [[Deletion (genetics)|deletion]] in [[Chromosome abnormality|chromosomal]] region [[:File:Angelman.PNG|15q11-13]] causing an absence of [[UBE3A|''UBE3A'' gene]], involving the [[Ubiquitin-protein ligase|ubiquitin pathway]].<ref name="Clayton-SmithPembrey1992">{{cite journal|last1=Clayton-Smith|first1=J|last2=Pembrey|first2=M E|title=Angelman syndrome.|journal=Journal of Medical Genetics|volume=29|issue=6|year=1992|pages=412–415|issn=1468-6244|doi=10.1136/jmg.29.6.412}}</ref><ref name="pmid194551853">{{cite journal |vauthors=Van Buggenhout G, Fryns JP |title=Angelman syndrome (AS, MIM 105830) |journal=Eur. J. Hum. Genet. |volume=17 |issue=11 |pages=1367–73 |date=November 2009 |pmid=19455185 |pmc=2986680 |doi=10.1038/ejhg.2009.67 |url=}}</ref><ref name="pmid22670133" />  There is a lack of [[Gene expression|expression]] of the [[maternally-inherited]] [[UBE3A|UBE3A gene]] in the brain, while the [[Paternally|paternally-inherited]] copy of [[UBE3A]] is [[Silencer (DNA)|silenced]].<ref name="pmid27860204">{{cite journal |vauthors=Tan WH, Bird LM |title=Angelman syndrome: Current and emerging therapies in 2016 |journal=Am J Med Genet C Semin Med Genet |volume=172 |issue=4 |pages=384–401 |date=December 2016 |pmid=27860204 |doi=10.1002/ajmg.c.31536 |url=}}</ref>
* Other causes include paternal [[uniparental disomy]], [[impringting]] error, [[Chromosomal translocation|translocation]], or single [[Mutation|gene mutation]] in ''UBE3A''.<ref>{{cite journal | author = Weeber E, Levenson J, Sweatt J | title = Molecular genetics of human cognition. | journal = Mol Interv | volume = 2 | issue = 6 | pages = 376-91, 339 | year = 2002 | id = PMID 14993414}}</ref>
*Other causes include paternal [[uniparental disomy]], [[impringting]] error, [[Chromosomal translocation|translocation]], or single [[Mutation|gene mutation]] in ''UBE3A''.<ref>{{cite journal | author = Weeber E, Levenson J, Sweatt J | title = Molecular genetics of human cognition. | journal = Mol Interv | volume = 2 | issue = 6 | pages = 376-91, 339 | year = 2002 | id = PMID 14993414}}</ref><ref name="pmid22670133" />
* 3-5% of cases of Angelman syndrome can be [[inherited]].<ref name=":1">{{Cite web|url=https://rarediseases.org/rare-diseases/angelman-syndrome/|title=Angelman Syndrome|last=Williams|first=Charles|date=|website=National Organization of Rare Diseases|archive-url=|archive-date=|dead-url=|access-date=06/02/2020}}</ref>
*3-5% of cases of Angelman syndrome can be [[inherited]].<ref name=":1">{{Cite web|url=https://rarediseases.org/rare-diseases/angelman-syndrome/|title=Angelman Syndrome|last=Williams|first=Charles|date=|website=National Organization of Rare Diseases|archive-url=|archive-date=|dead-url=|access-date=06/02/2020}}</ref><ref name="pmid194551854">{{cite journal |vauthors=Van Buggenhout G, Fryns JP |title=Angelman syndrome (AS, MIM 105830) |journal=Eur. J. Hum. Genet. |volume=17 |issue=11 |pages=1367–73 |date=November 2009 |pmid=19455185 |pmc=2986680 |doi=10.1038/ejhg.2009.67 |url=}}</ref>
* In approximately 10% of cases, no cause can be identified.<ref name=":1" />
*[[Recurrence quantification analysis|Recurrence]] of Angelman syndrome in subsequent children when having a child with a ''[[De novo mutation|de novo]]'' [[Deletion (genetics)|deletion]] is estimated around 1%.<ref name="pmid194551855">{{cite journal |vauthors=Van Buggenhout G, Fryns JP |title=Angelman syndrome (AS, MIM 105830) |journal=Eur. J. Hum. Genet. |volume=17 |issue=11 |pages=1367–73 |date=November 2009 |pmid=19455185 |pmc=2986680 |doi=10.1038/ejhg.2009.67 |url=}}</ref>
*In approximately 10% of cases, no cause can be identified.<ref name=":1" />


=== Phenotype-Gene Relationships ===
===Phenotype-Gene Relationships===
{| class="wikitable"
{| class="wikitable"
!Phenotype
!Phenotype
Line 48: Line 50:
|15q11-15q13
|15q11-15q13
|}<br />
|}<br />
== Clinical Features ==
==Clinical Features==
Angelman syndrome is characterized by:
Angelman syndrome is characterized by:


* [[Puppet-like movement]]<ref name=":0" /><ref name="pmid145106232" />
*[[Puppet-like movement]]<ref name=":0">{{Cite book|title=Deletion Syndromes/ Step up to USMLE step 2CK|last=Jenkins|first=Brian|publisher=Wolters Kluwer|year=2016|isbn=978-1496309747|location=Fort Worth, Texas|pages=291}}</ref><ref name="pmid145106232" /><ref name="pmid22670133" /><ref name="pmid20445456" />
* [[Cognitive delay|Intelectual]] and [[development delay]]<ref name=":0" />
*[[Cognitive delay|Intelectual]] and [[development delay]]<ref name=":0" /><ref name="pmid194551852">{{cite journal |vauthors=Van Buggenhout G, Fryns JP |title=Angelman syndrome (AS, MIM 105830) |journal=Eur. J. Hum. Genet. |volume=17 |issue=11 |pages=1367–73 |date=November 2009 |pmid=19455185 |pmc=2986680 |doi=10.1038/ejhg.2009.67 |url=}}</ref><ref name="pmid22670133" /><ref name="pmid20445456" />
* [[Seizure|Seizures]]<ref name=":0" />
*[[Seizure|Seizures]]<ref name=":0" /><ref name="pmid22670133" /><ref name="pmid20445456" />
* Unprovoked [[laughter]]/[[Smile|smiling]]<ref name=":0" /><ref name="pmid145106232">{{cite journal |vauthors=Guerrini R, Carrozzo R, Rinaldi R, Bonanni P |title=Angelman syndrome: etiology, clinical features, diagnosis, and management of symptoms |journal=Paediatr Drugs |volume=5 |issue=10 |pages=647–61 |date=2003 |pmid=14510623 |doi=10.2165/00148581-200305100-00001 |url=}}</ref>
*Unprovoked [[laughter]]/[[Smile|smiling]]<ref name=":0" /><ref name="pmid145106232">{{cite journal |vauthors=Guerrini R, Carrozzo R, Rinaldi R, Bonanni P |title=Angelman syndrome: etiology, clinical features, diagnosis, and management of symptoms |journal=Paediatr Drugs |volume=5 |issue=10 |pages=647–61 |date=2003 |pmid=14510623 |doi=10.2165/00148581-200305100-00001 |url=}}</ref>
* Excessive [[socialization]] with strangers<ref name=":0" />
*Excessive [[socialization]] with strangers<ref name=":0" />
*[[Speech and language pathology|Speech impairment]]<ref name="pmid145106232" />
*[[Speech and language pathology|Speech impairment]]<ref name="pmid145106232" /><ref name="pmid22670133" /><ref name="pmid20445456" />


Other less common features are:
Other less common features are:


* Delayed [[Head circumference growth|head circumference]] growth<ref name="SidorovDeck20172" />
*Delayed [[Head circumference growth|head circumference]] growth<ref name="SidorovDeck20172" />


* [[Suction|Suck]]/[[swallowing]] disorders<ref name="SidorovDeck20172" />
*[[Suction|Suck]]/[[swallowing]] disorders<ref name="SidorovDeck20172" /><ref name="pmid20445456" />
* [[Feeding]] problems<ref name="SidorovDeck20172" />
*[[Feeding]] problems<ref name="SidorovDeck20172" />
* Frequent [[drooling]]<ref name="SidorovDeck20172" />
*Frequent [[drooling]]<ref name="SidorovDeck20172" />
* Excessive [[Mastication|chewing]]<ref name="SidorovDeck20172" />
*Excessive [[Mastication|chewing]]<ref name="SidorovDeck20172" />
* [[Gait abnormality|Wide based gait]]<ref name="SidorovDeck20172" /><ref name="pmid145106232" />
*[[Gait abnormality|Wide based gait]]<ref name="SidorovDeck20172" /><ref name="pmid145106232" />
* Increased [[Hyperesthesia|sensitivity to heat]]<ref name="SidorovDeck20172" />
*Increased [[Hyperesthesia|sensitivity to heat]]<ref name="SidorovDeck20172" />
* [[Insomnia|Diminished need for sleep]]<ref name="SidorovDeck20172" />
*[[Insomnia|Diminished need for sleep]]<ref name="SidorovDeck20172" />
* Hydrophilia<ref name="SidorovDeck20172" />
*Hydrophilia<ref name="SidorovDeck20172" />
* Fascination with crinkly things<ref name="SidorovDeck20172" />
*Fascination with crinkly things<ref name="SidorovDeck20172" />
* Abnormal [[feeding]] conducts<ref name="SidorovDeck20172" />
*Abnormal [[feeding]] conducts<ref name="SidorovDeck20172" />
* [[Constipation]]<ref name="SidorovDeck20172" />
*[[Constipation]]<ref name="SidorovDeck20172" />


<br />
==Differentiating {{PAGENAME}} from Other Diseases==
==Differentiating {{PAGENAME}} from Other Diseases==
Angelman syndrome must be differentiated from other diseases that cause intelectual and development delay, dismorfic facies, seizures and/or deletion in chromosome 15, such as:
Angelman syndrome must be differentiated from other [[Genetic diseases|diseases]] that cause intelectual and [[development]] delay, [[Dysmorphic feature|dysmorphic facies]], and [[Seizure|seizures]], such as:
{|
{|
|- style="background: #4479BA; color: #FFFFFF; text-align: center;"
|- style="background: #4479BA; color: #FFFFFF; text-align: center;"
Line 90: Line 93:
|-
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Leigh syndrome]]
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Leigh syndrome]]
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" |<nowiki>+</nowiki>
| style="background: #F5F5F5; padding: 5px;" |<nowiki>+</nowiki>
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
* Progressive [[psychomotor]] regression
*Progressive [[psychomotor]] regression
*[[Seizures]]
*[[Seizures]]
* External [[ophthalmoplegia]]
*External [[ophthalmoplegia]]
*[[Lactic acidosis]]
*[[Lactic acidosis]]
*[[Vomiting]]
*[[Vomiting]]
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
* Increased [[lactate]] levels in [[blood]] and [[CSF]]
*Increased [[lactate]] levels in [[blood]] and [[CSF]]
* Genetic testing
*Genetic testing
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
* MRI: abnormal [[white matter]] signal in the [[putamen]], [[basal ganglia]], and [[brainstem]] on T2 images
*MRI: abnormal [[white matter]] signal in the [[putamen]], [[basal ganglia]], and [[brainstem]] on T2 images
|-
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Niemann-Pick]] disease type C
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Niemann-Pick]] disease type C
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
* Progressive [[neurodegeneration]]
*Progressive [[neurodegeneration]]
*[[Hepatosplenomegaly]]
*[[Hepatosplenomegaly]]
* Systemic involvement of [[liver]], [[spleen]], or [[lung]] preceedes [[neurologic]] symptoms
*Systemic involvement of [[liver]], [[spleen]], or [[lung]] preceedes [[neurologic]] symptoms
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
* Abnormal [[liver]] function tests
*Abnormal [[liver]] function tests
*[[Fibroblast]] cell culture with filipin staining
*[[Fibroblast]] cell culture with filipin staining
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
* MRI:
*MRI:
**[[Cerebral]] and [[cerebellar]] [[atrophy]]
**[[Cerebral]] and [[cerebellar]] [[atrophy]]
**Thinning of the [[corpus callosum]]
**Thinning of the [[corpus callosum]]
|-
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Infantile Refsum disease
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Infantile Refsum disease
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
* Abnormalities of the [[optic nerve]] and disc
*Abnormalities of the [[optic nerve]] and disc
*[[Retinitis pigmentosa]]
*[[Retinitis pigmentosa]]
*[[Sensorineural]] hearing loss
*[[Sensorineural]] hearing loss
Line 138: Line 141:
|-
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Adrenoleukodystrophy]]
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Adrenoleukodystrophy]]
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
*[[Cognitive]] and behavioral abnormalities
*[[Cognitive]] and behavioral abnormalities
Line 149: Line 152:
*[[Neurologic]] deterioration progresses at a variable rate
*[[Neurologic]] deterioration progresses at a variable rate
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
* Elevated plasma VLCFA levels
*Elevated plasma VLCFA levels
* Molecular [[genetic testing]] for mutations in the ABCD1 gene
*Molecular [[genetic testing]] for mutations in the ABCD1 gene
| style="background: #F5F5F5; padding: 5px; text-align: center;" | --
| style="background: #F5F5F5; padding: 5px; text-align: center;" | --
|-
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Zellweger syndrome]]
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Zellweger syndrome]]
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
*[[Craniofacial]] dysmorphism
*[[Craniofacial]] dysmorphism
*[[Hepatomegaly]]
*[[Hepatomegaly]]
* Neonatal [[seizures]]
*Neonatal [[seizures]]
* Profound developmental delay
*Profound developmental delay
*[[MRI]] findings include [[cortical]] and [[white matter]] abnormalities
*[[MRI]] findings include [[cortical]] and [[white matter]] abnormalities
*[[Neurologic deterioration]] is rapid and infants rarely survive beyond six months of age
*[[Neurologic deterioration]] is rapid and infants rarely survive beyond six months of age
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
* Elevated plasma VLCFA levels
*Elevated plasma VLCFA levels
* Elevated levels of [[phytanic acid]], pristanic acid, and pipecolic acid in plasma and [[fibroblasts]]
*Elevated levels of [[phytanic acid]], pristanic acid, and pipecolic acid in plasma and [[fibroblasts]]
* Reduced plasmalogen in [[erythrocytes]]
*Reduced plasmalogen in [[erythrocytes]]
* Molecular [[genetic]] testing for [[mutations]] in the PEX1 or PEX6 genes
*Molecular [[genetic]] testing for [[mutations]] in the PEX1 or PEX6 genes
| style="background: #F5F5F5; padding: 5px; text-align: center;" | --
| style="background: #F5F5F5; padding: 5px; text-align: center;" | --
|-
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Pyruvate dehydrogenase deficiency]]
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Pyruvate dehydrogenase deficiency]]
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
*[[Lactic acidosis]]
*[[Lactic acidosis]]
Line 182: Line 185:
*[[Intellectual disability]]
*[[Intellectual disability]]
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
* Elevated [[lactate]] and pyruvate levels in [[blood]] and CSF
*Elevated [[lactate]] and pyruvate levels in [[blood]] and CSF
* Abnormal PDH enzymatic activity in cultured fibroblasts
*Abnormal PDH enzymatic activity in cultured fibroblasts
| style="background: #F5F5F5; padding: 5px; text-align: center;" | --
| style="background: #F5F5F5; padding: 5px; text-align: center;" | --
|-
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Arginase deficiency]]
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Arginase deficiency]]
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
*[[Hyperammonemia]]
*[[Hyperammonemia]]
Line 196: Line 199:
*[[Respiratory alkalosis]]
*[[Respiratory alkalosis]]
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
* Elevated [[ammonia]] level
*Elevated [[ammonia]] level
* Elevated [[arginine]] level
*Elevated [[arginine]] level
| style="background: #F5F5F5; padding: 5px; text-align: center;" | --
| style="background: #F5F5F5; padding: 5px; text-align: center;" | --
|-
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Holocarboxylase synthetase deficiency
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Holocarboxylase synthetase deficiency
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
*[[Ketoacidosis]]
*[[Ketoacidosis]]
Line 213: Line 216:
| style="background: #F5F5F5; padding: 5px;" |Elevated levels of:
| style="background: #F5F5F5; padding: 5px;" |Elevated levels of:


* Beta-hydroxyisovalerate
*Beta-hydroxyisovalerate
* Beta-methylcrotonylglycine
*Beta-methylcrotonylglycine
* Beta-hydroxypropionate
*Beta-hydroxypropionate
* Methylcitrate
*Methylcitrate
* Tiglylglycine
*Tiglylglycine
| style="background: #F5F5F5; padding: 5px; text-align: center;" | --
| style="background: #F5F5F5; padding: 5px; text-align: center;" | --
|-
|-
Line 226: Line 229:
| style="background: #F5F5F5; padding: 5px;" |<nowiki>+</nowiki>
| style="background: #F5F5F5; padding: 5px;" |<nowiki>+</nowiki>
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
* Episodes of [[metabolic decompensation]] and [[encephalopathy]] often precipitated by [[infection]] and [[fever]]
*Episodes of [[metabolic decompensation]] and [[encephalopathy]] often precipitated by [[infection]] and [[fever]]
* Rarely presents in the newborn period
*Rarely presents in the newborn period
* Microencephalic [[macrocephaly]]
*Microencephalic [[macrocephaly]]
*[[Seizures]] (approximately 20 percent)
*[[Seizures]] (approximately 20 percent)
*[[Cognitive function]] is preserved
*[[Cognitive function]] is preserved
Line 234: Line 237:


*[[glutaric acid]]
*[[glutaric acid]]
* 3-hydroxyglutaric acid
*3-hydroxyglutaric acid
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
* MRI:
*MRI:
**[[Frontal]] and [[temporal]] [[atrophy]]
**[[Frontal]] and [[temporal]] [[atrophy]]
|-
|-
Line 245: Line 248:
| style="background: #F5F5F5; padding: 5px;" |<nowiki>-</nowiki>
| style="background: #F5F5F5; padding: 5px;" |<nowiki>-</nowiki>
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
* Progressive [[cerebellar]] [[ataxia]]
*Progressive [[cerebellar]] [[ataxia]]
* Abnormal eye movements
*Abnormal eye movements
*[[Oculocutaneous]] [[telangiectasias]]
*[[Oculocutaneous]] [[telangiectasias]]
* Immune deficiency
*Immune deficiency
* Increased risk of [[malignancy]]
*Increased risk of [[malignancy]]
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
* Elevated serum alpha-fetoprotein level
*Elevated serum alpha-fetoprotein level
* Low [[IgA]] and [[IgG]] levels
*Low [[IgA]] and [[IgG]] levels
*[[Lymphopenia]]
*[[Lymphopenia]]
* Genetic testing for [[mutation]] in the ATM gene
*Genetic testing for [[mutation]] in the ATM gene
| style="background: #F5F5F5; padding: 5px; text-align: center;" | --
| style="background: #F5F5F5; padding: 5px; text-align: center;" | --
|-
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Pontocerebellar]] [[hypoplasias]]
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Pontocerebellar]] [[hypoplasias]]
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
* Progressive muscle [[atrophy]]
*Progressive muscle [[atrophy]]
*[[Microcephaly]]
*[[Microcephaly]]
*[[Developmental delay]]
*[[Developmental delay]]
| style="background: #F5F5F5; padding: 5px;" |[[Genetic]] testing for PCH gene mutations
| style="background: #F5F5F5; padding: 5px;" |[[Genetic]] testing for PCH gene mutations
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
* MRI :
*MRI :
**Small [[cerebellum]] and [[brainstem]] including the [[pons]]
**Small [[cerebellum]] and [[brainstem]] including the [[pons]]
|-
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Metachromatic leukodystrophy]]
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Metachromatic leukodystrophy]]
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
* Regression of motor skills
*Regression of motor skills
*[[Seizures]]
*[[Seizures]]
*[[Optic atrophy]]
*[[Optic atrophy]]
* Reduced or absent [[deep tendon reflexes]]
*Reduced or absent [[deep tendon reflexes]]
*[[Intellectual disability]]
*[[Intellectual disability]]
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
* Deficient arylsulfatase A enzyme activity in [[leukocytes]] or cultured skin fibroblasts
*Deficient arylsulfatase A enzyme activity in [[leukocytes]] or cultured skin fibroblasts
| style="background: #F5F5F5; padding: 5px; text-align: center;" | --
| style="background: #F5F5F5; padding: 5px; text-align: center;" | --
|-
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Pelizaeus-Merzbacher]]
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Pelizaeus-Merzbacher]]
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
*[[Nystagmus]]
*[[Nystagmus]]
*[[Cognitive impairment]]
*[[Cognitive impairment]]
* Onset in infancy
*Onset in infancy
* Slowly progressive
*Slowly progressive
* Language development may be normal
*Language development may be normal
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
*[[Genetic]] testing for [[mutations]] in PLP1 gene
*[[Genetic]] testing for [[mutations]] in PLP1 gene
Line 304: Line 307:
|-
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Angelman syndrome]]
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Angelman syndrome]]
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
* Profound [[intellectual disability]]
*Profound [[intellectual disability]]
* Postnatal [[microcephaly]]
*Postnatal [[microcephaly]]
* Typical abnormal behaviors (paroxysmal laughter, easily excitable)
*Typical abnormal behaviors (paroxysmal laughter, easily excitable)
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
* Methylation studies and [[chromosome]] microarray to detect chromosome 15 anomalies and UBE3A mutations
*Methylation studies and [[chromosome]] microarray to detect chromosome 15 anomalies and UBE3A mutations
| style="background: #F5F5F5; padding: 5px; text-align: center;" | --
| style="background: #F5F5F5; padding: 5px; text-align: center;" | --
|-
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Rett syndrome]]
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Rett syndrome]]
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
* Occurs almost exclusively in females
*Occurs almost exclusively in females
* Normal development during first six months followed by regression and loss of milestones
*Normal development during first six months followed by regression and loss of milestones
* Loss of speech capability
*Loss of speech capability
* Stereotypic hand movements
*Stereotypic hand movements
*[[Seizures]]
*[[Seizures]]
*[[Autistic]] features
*[[Autistic]] features
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
* Clinical diagnosis
*Clinical diagnosis
*[[Genetic]] testing for MECP2 mutations
*[[Genetic]] testing for MECP2 mutations
| style="background: #F5F5F5; padding: 5px; text-align: center;" | --
| style="background: #F5F5F5; padding: 5px; text-align: center;" | --
|-
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Lesch-Nyhan syndrome]]
| style="background: #DCDCDC; padding: 5px; text-align: center;" |[[Lesch-Nyhan syndrome]]
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
*[[Self-mutilating]] behavior
*[[Self-mutilating]] behavior
*[[Urinary]] stones due to [[hyperuricemia]]
*[[Urinary]] stones due to [[hyperuricemia]]
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
* Elevated [[uric acid]] level
*Elevated [[uric acid]] level
* Abnormal enzymatic activity of HPRT in cultured fibroblasts
*Abnormal enzymatic activity of HPRT in cultured fibroblasts
*[[Genetic]] testing for HPRT gene [[mutations]]
*[[Genetic]] testing for HPRT gene [[mutations]]
| style="background: #F5F5F5; padding: 5px; text-align: center;" | --
| style="background: #F5F5F5; padding: 5px; text-align: center;" | --
|-
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Miller-Dieker lissencephaly
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Miller-Dieker lissencephaly
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
*[[Lissencephaly]]
*[[Lissencephaly]]
Line 357: Line 360:
*[[Dysmorphic]] features
*[[Dysmorphic]] features
*[[Seizures]]
*[[Seizures]]
* Failure to thrive
*Failure to thrive
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
* Cytogenetic testing for 17p13.3 microdeletion
*Cytogenetic testing for 17p13.3 microdeletion
| style="background: #F5F5F5; padding: 5px; text-align: center;" | --
| style="background: #F5F5F5; padding: 5px; text-align: center;" | --
|-
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Dopa-responsive [[dystonia]]
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Dopa-responsive [[dystonia]]
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | -
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" | +
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
* Onset in early childhood
*Onset in early childhood
* Symptoms worsen with [[fatigue]] and exercise
*Symptoms worsen with [[fatigue]] and exercise
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
* Positive response to a trial of [[levodopa]]
*Positive response to a trial of [[levodopa]]
| style="background: #F5F5F5; padding: 5px; text-align: center;" | --
| style="background: #F5F5F5; padding: 5px; text-align: center;" | --
|}
|}
Line 378: Line 381:
==Epidemiology and Demographics==
==Epidemiology and Demographics==


* The [[prevalence]] of Angelman syndrome is approximately 5-7 per 100,000 individuals worldwide.<ref name="Clayton-SmithPembrey19925">{{cite journal|last1=Clayton-Smith|first1=J|last2=Pembrey|first2=M E|title=Angelman syndrome.|journal=Journal of Medical Genetics|volume=29|issue=6|year=1992|pages=412–415|issn=1468-6244|doi=10.1136/jmg.29.6.412}}</ref>
*The [[prevalence]] of Angelman syndrome is approximately 5-7 per 100,000 individuals worldwide.<ref name="Clayton-SmithPembrey19925">{{cite journal|last1=Clayton-Smith|first1=J|last2=Pembrey|first2=M E|title=Angelman syndrome.|journal=Journal of Medical Genetics|volume=29|issue=6|year=1992|pages=412–415|issn=1468-6244|doi=10.1136/jmg.29.6.412}}</ref>
* The exact [[Incidence (epidemiology)|incidence]] of Angelman syndrome is unknown, but its estimated to be between 6-7 per 100,000 births .<ref name="urlwww.angelman.org2">{{cite web |url=https://www.angelman.org/wp-content/uploads/2019/12/facts_about_as_2009_3-19-10.pdf |title=www.angelman.org |format= |work= |accessdate=}}</ref>
*The exact [[Incidence (epidemiology)|incidence]] of Angelman syndrome is unknown, but its estimated to be between 6-7 per 100,000 births .<ref name="urlwww.angelman.org2">{{cite web |url=https://www.angelman.org/wp-content/uploads/2019/12/facts_about_as_2009_3-19-10.pdf |title=www.angelman.org |format= |work= |accessdate=}}</ref>


=== Age ===
===Age===
Full [[Spectrum disorder|spectrum]] of the disease appears usually before 3 years of age.<ref name="urlAngelman syndrome - Symptoms and causes - Mayo Clinic">{{cite web |url=https://www.mayoclinic.org/diseases-conditions/angelman-syndrome/symptoms-causes/syc-20355621#:~:text=Developmental%20delays%2C%20which%20begin%20between,2%20and%203%20years%20old. |title=Angelman syndrome - Symptoms and causes - Mayo Clinic |format= |work= |accessdate=}}</ref>
Full [[Spectrum disorder|spectrum]] of the disease appears usually before 3 years of age.<ref name="urlAngelman syndrome - Symptoms and causes - Mayo Clinic">{{cite web |url=https://www.mayoclinic.org/diseases-conditions/angelman-syndrome/symptoms-causes/syc-20355621#:~:text=Developmental%20delays%2C%20which%20begin%20between,2%20and%203%20years%20old. |title=Angelman syndrome - Symptoms and causes - Mayo Clinic |format= |work= |accessdate=}}</ref>


=== Gender ===
===Gender===
Angelman syndrome affects men and women equally.<ref name="Clayton-SmithPembrey19925" /><ref name="pmid26942024">{{cite journal |vauthors=Luk HM |title=Angelman-Like Syndrome: A Genetic Approach to Diagnosis with Illustrative Cases |journal=Case Rep Genet |volume=2016 |issue= |pages=9790169 |date=2016 |pmid=26942024 |pmc=4749774 |doi=10.1155/2016/9790169 |url=}}</ref>
Angelman syndrome affects men and women equally.<ref name="Clayton-SmithPembrey19925" /><ref name="pmid26942024">{{cite journal |vauthors=Luk HM |title=Angelman-Like Syndrome: A Genetic Approach to Diagnosis with Illustrative Cases |journal=Case Rep Genet |volume=2016 |issue= |pages=9790169 |date=2016 |pmid=26942024 |pmc=4749774 |doi=10.1155/2016/9790169 |url=}}</ref>


=== Race ===
===Race===
There is no [[Race|racial predilection]] for Angelman syndrome.<ref name="urlAngelmans Syndrome - symptoms, average, Definition, Description, Demographics, Causes and symptoms, Diagnosis2" />
There is no [[Race|racial predilection]] for Angelman syndrome.<ref name="urlAngelmans Syndrome - symptoms, average, Definition, Description, Demographics, Causes and symptoms, Diagnosis2" />
<br />
<br />
==Risk Factors==
==Risk Factors==
There are no [[Risk factor|risk factors]] for developing Angelman syndrome, since most of the cases occur due to a [[De novo mutation|de novo]] [[Deletion (genetics)|deletion]] and there is a very small chance for this condition to be [[Heredity|hereditary]] transmitted.<ref name="pmid14510623">{{cite journal |vauthors=Guerrini R, Carrozzo R, Rinaldi R, Bonanni P |title=Angelman syndrome: etiology, clinical features, diagnosis, and management of symptoms |journal=Paediatr Drugs |volume=5 |issue=10 |pages=647–61 |date=2003 |pmid=14510623 |doi=10.2165/00148581-200305100-00001 |url=}}</ref>
There are no [[Risk factor|risk factors]] for developing Angelman syndrome, since most of the cases occur due to a [[De novo mutation|''de novo'']] [[Deletion (genetics)|deletion]] and there is a very small chance for this condition to be [[Heredity|hereditary]] transmitted.<ref name="pmid14510623">{{cite journal |vauthors=Guerrini R, Carrozzo R, Rinaldi R, Bonanni P |title=Angelman syndrome: etiology, clinical features, diagnosis, and management of symptoms |journal=Paediatr Drugs |volume=5 |issue=10 |pages=647–61 |date=2003 |pmid=14510623 |doi=10.2165/00148581-200305100-00001 |url=}}</ref>
 
==Screening==
[[Prenatal]] [[Screening test|screening]] of [[15q11.2-q13]] region [[Mutation|mutations]] is possible through [[DNA]] and/or [[chromosomal]]/[[Fluorescence in situ hybridization|FISH analysis]] of [[fetal]] cells acquired by [[chorionic villus sampling]] or [[amniocentesis]].<ref name="pmid20445456" />


== Screening ==
[[Screening test|Screening]] for Angelman syndrome-suspected patients can be made by the following tests:
[[Screening test|Screening]] for Angelman syndrome can be made by the following tests:


* [[Karyotyping]]. Is warranted for any patient with suspected Angelman syndrome.<ref name="pmid145106233" />
*[[Karyotyping]]. Is warranted for any patient with suspected Angelman syndrome.<ref name="pmid145106233" />
* [[Fluorescence in situ hybridization|Fluorescent in situ hybridization (FISH)]]. May detect [[Deletion (genetics)|deletions]], but not [[Genomic imprinting|imprinting]] centers or [[uniparental disomy]].<ref name="pmid145106233" />
*[[Fluorescence in situ hybridization|Fluorescent in situ hybridization (FISH)]]. May detect [[Deletion (genetics)|deletions]], but not [[Genomic imprinting|imprinting]] centers or [[uniparental disomy]].<ref name="pmid145106233" />
* [[Methylation]] test. May detect [[Deletion (genetics)|deletions]], [[Uniparental disomy|uniparental disomies]], and [[Genomic imprinting|imprinting mutations]], but not [[UBE3A|UBE3A gene]] [[mutation]].<ref name="pmid145106233" />
*[[Methylation]] test. May detect [[Deletion (genetics)|deletions]], [[Uniparental disomy|uniparental disomies]], and [[Genomic imprinting|imprinting mutations]], but not [[UBE3A|UBE3A gene]] [[mutation]].<ref name="pmid145106233" />
* [[Paternal mtDNA transmission|Paternal]] [[Uniparental disomy|uniparental disomy (UPD)]] studies. Usually done after a normal [[Fluorescence in situ hybridization|FISH]] and [[methylation]] test.<ref name="pmid145106233" />
*[[Paternal mtDNA transmission|Paternal]] [[Uniparental disomy|uniparental disomy (UPD)]] studies. Usually done after a normal [[Fluorescence in situ hybridization|FISH]] and [[methylation]] test.<ref name="pmid145106233" />
* [[UBE3A|Ubiquitin-protein ligase E3A (UBE3A)]] [[mutations]]. Is performed in patients with clinical presentation of Angelman syndrome, but negative [[Methylation specific oligonucleotide microarray|methylation]] test.<ref name="pmid145106233" />
*[[UBE3A|Ubiquitin-protein ligase E3A (UBE3A)]] [[mutations]]. Is performed in patients with clinical presentation of Angelman syndrome, but negative [[Methylation specific oligonucleotide microarray|methylation]] test.<ref name="pmid145106233" />
* [[Genomic imprinting|Imprinting]] center (IC) [[mutations]]. Detects small [[Deletion (genetics)|deletions]], but is only available in research centers.<ref name="pmid145106233">{{cite journal |vauthors=Guerrini R, Carrozzo R, Rinaldi R, Bonanni P |title=Angelman syndrome: etiology, clinical features, diagnosis, and management of symptoms |journal=Paediatr Drugs |volume=5 |issue=10 |pages=647–61 |date=2003 |pmid=14510623 |doi=10.2165/00148581-200305100-00001 |url=}}</ref>
*[[Genomic imprinting|Imprinting]] center (IC) [[mutations]]. Detects small [[Deletion (genetics)|deletions]], but is only available in research centers.<ref name="pmid145106233">{{cite journal |vauthors=Guerrini R, Carrozzo R, Rinaldi R, Bonanni P |title=Angelman syndrome: etiology, clinical features, diagnosis, and management of symptoms |journal=Paediatr Drugs |volume=5 |issue=10 |pages=647–61 |date=2003 |pmid=14510623 |doi=10.2165/00148581-200305100-00001 |url=}}</ref>


<br />
<br />
Line 407: Line 412:


*[[Newborns]] with Angelman syndrome usually [[weight]] less than [[averange]] when delivered.<ref name="urlwww.ncbi.nlm.nih.gov">{{cite web |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1015993/pdf/jmedgene00020-0054.pdf |title=www.ncbi.nlm.nih.gov |format= |work= |accessdate=}}</ref>
*[[Newborns]] with Angelman syndrome usually [[weight]] less than [[averange]] when delivered.<ref name="urlwww.ncbi.nlm.nih.gov">{{cite web |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1015993/pdf/jmedgene00020-0054.pdf |title=www.ncbi.nlm.nih.gov |format= |work= |accessdate=}}</ref>
*[[Motor delay]] and [[jerky movements]] usually appear before 1 year of age.<ref name="urlwww.ncbi.nlm.nih.gov" />
*[[Motor delay]] and [[jerky movements]] usually appear before 1 year of age.<ref name="urlwww.ncbi.nlm.nih.gov" /><ref name="pmid22670133" />
*[[Seizure|Seizures]] could be present between 2 and 8 years of age.<ref name="urlwww.ncbi.nlm.nih.gov" />
*[[Seizure|Seizures]] could be present between 2 and 8 years of age.<ref name="urlwww.ncbi.nlm.nih.gov" /><ref name="pmid22670133" />
*[[Dysmorphic feature|Dysmorphic facies]] and scoliosis are aparent after 5 years of age.<ref name="urlwww.ncbi.nlm.nih.gov" /><ref name="pmid9072912">{{cite journal |author=Laan LA, den Boer AT, Hennekam RC, Renier WO, Brouwer OF |title=Angelman syndrome in adulthood |journal=Am. J. Med. Genet. |volume=66 |issue=3 |pages=356-60 |year=1996 |pmid=9072912 | doi=10.1002/(SICI)1096-8628(19961218)66:3%3C356::AID-AJMG21%3E3.0.CO;2-K}}</ref><ref name="pmid90729122">{{cite journal |vauthors=Laan LA, den Boer AT, Hennekam RC, Renier WO, Brouwer OF |title=Angelman syndrome in adulthood |journal=Am. J. Med. Genet. |volume=66 |issue=3 |pages=356–60 |date=December 1996 |pmid=9072912 |doi=10.1002/(SICI)1096-8628(19961218)66:3<356::AID-AJMG21>3.0.CO;2-K |url=}}</ref>
*[[Dysmorphic feature|Dysmorphic facies]] and scoliosis are aparent after 5 years of age.<ref name="urlwww.ncbi.nlm.nih.gov" /><ref name="pmid9072912">{{cite journal |author=Laan LA, den Boer AT, Hennekam RC, Renier WO, Brouwer OF |title=Angelman syndrome in adulthood |journal=Am. J. Med. Genet. |volume=66 |issue=3 |pages=356-60 |year=1996 |pmid=9072912 | doi=10.1002/(SICI)1096-8628(19961218)66:3%3C356::AID-AJMG21%3E3.0.CO;2-K}}</ref><ref name="pmid90729122">{{cite journal |vauthors=Laan LA, den Boer AT, Hennekam RC, Renier WO, Brouwer OF |title=Angelman syndrome in adulthood |journal=Am. J. Med. Genet. |volume=66 |issue=3 |pages=356–60 |date=December 1996 |pmid=9072912 |doi=10.1002/(SICI)1096-8628(19961218)66:3<356::AID-AJMG21>3.0.CO;2-K |url=}}</ref><ref name="pmid22670133" />
*[[Tanner staging|Sexual developement]] begins and progresses at a normal time.<ref>{{cite journal | author = Lossie A, Driscoll D | title = Transmission of Angelman syndrome by an affected mother. | journal = Genet Med | volume = 1 | issue = 6 | pages = 262-6 | year = | id = PMID 11258627}}</ref><ref name="pmid11258627">{{cite journal |vauthors=Lossie AC, Driscoll DJ |title=Transmission of Angelman syndrome by an affected mother |journal=Genet. Med. |volume=1 |issue=6 |pages=262–6 |date=1999 |pmid=11258627 |doi=10.1097/00125817-199909000-00004 |url=}}</ref>
*[[Tanner staging|Sexual developement]] begins and progresses at a normal time.<ref>{{cite journal | author = Lossie A, Driscoll D | title = Transmission of Angelman syndrome by an affected mother. | journal = Genet Med | volume = 1 | issue = 6 | pages = 262-6 | year = | id = PMID 11258627}}</ref><ref name="pmid11258627">{{cite journal |vauthors=Lossie AC, Driscoll DJ |title=Transmission of Angelman syndrome by an affected mother |journal=Genet. Med. |volume=1 |issue=6 |pages=262–6 |date=1999 |pmid=11258627 |doi=10.1097/00125817-199909000-00004 |url=}}</ref>
* Dressing skills and use of certain utensils may happen.<ref name="pmid9072912" />
*Dressing skills and use of certain utensils may happen.<ref name="pmid9072912" />
* Patients never develope [[Language acquisition|language]] and usually comunicate with signs.<ref name="urlwww.ncbi.nlm.nih.gov" />
*Patients never develope proper [[Language acquisition|language]] (5-10 learned word) and usually comunicate with signs.<ref name="urlwww.ncbi.nlm.nih.gov" /><ref name="pmid22670133" /><ref name="pmid11432411" />
* At the end, patients do not acquiere enough abilities to live by there own.<ref name="urlwww.ncbi.nlm.nih.gov" />
*At the end, patients do not acquire enough abilities to live by there own.<ref name="urlwww.ncbi.nlm.nih.gov" />
* The [[Mortality rate|mortality]] rate of Angelman syndrome per 1000 patients/year was 15.84.<ref name="HerbstByard2012">{{cite journal|last1=Herbst|first1=Jonathon|last2=Byard|first2=Roger W.|title=Sudden Death and Angelman Syndrome|journal=Journal of Forensic Sciences|volume=57|issue=1|year=2012|pages=257–259|issn=00221198|doi=10.1111/j.1556-4029.2011.01901.x}}</ref>
*[[Prognosis]] will vary depending on the severity of [[Symptoms and Signs|symptoms]] and earliness of management.<ref name="pmid28494826">{{cite journal |vauthors=Bonello D, Camilleri F, Calleja-Agius J |title=Angelman Syndrome: Identification and Management |journal=Neonatal Netw |volume=36 |issue=3 |pages=142–151 |date=May 2017 |pmid=28494826 |doi=10.1891/0730-0832.36.3.142 |url=}}</ref>
*Patients may have a normal [[life span]].<ref name="pmid28494826" />
*The [[Mortality rate|mortality]] rate of Angelman syndrome per 1000 patients/year was 15.84.<ref name="HerbstByard2012">{{cite journal|last1=Herbst|first1=Jonathon|last2=Byard|first2=Roger W.|title=Sudden Death and Angelman Syndrome|journal=Journal of Forensic Sciences|volume=57|issue=1|year=2012|pages=257–259|issn=00221198|doi=10.1111/j.1556-4029.2011.01901.x}}</ref>


<br />
<br />
Line 420: Line 427:
==Diagnosis==
==Diagnosis==


=== Diagnostic Criteria ===
===Diagnostic Criteria===
The Angelman Syndrome Foundation defined criteria for diagnosis in 1995, and updated his criteria in 2006.<ref name="pmid7625452">{{cite journal |author=Williams CA, Angelman H, Clayton-Smith J, ''et al'' |title=Angelman syndrome: consensus for diagnostic criteria. Angelman Syndrome Foundation |journal=Am. J. Med. Genet. |volume=56 |issue=2 |pages=237-8 |year=1995 |pmid=7625452 |doi=10.1002/ajmg.1320560224}}</ref>


* The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met:
The [[diagnosis]] of Angelman syndrome according to the Scientific Advisory Committee of the US Angelman syndrome Foundation (Williams ''et al'' 2006) is based on:<ref name="pmid164707472">{{cite journal |vauthors=Williams CA, Beaudet AL, Clayton-Smith J, Knoll JH, Kyllerman M, Laan LA, Magenis RE, Moncla A, Schinzel AA, Summers JA, Wagstaff J |title=Angelman syndrome 2005: updated consensus for diagnostic criteria |journal=Am. J. Med. Genet. A |volume=140 |issue=5 |pages=413–8 |date=March 2006 |pmid=16470747 |doi=10.1002/ajmg.a.31074 |url=}}</ref><ref name="pmid194551856" /><ref name="pmid16470747">{{cite journal |author=Williams CA, Beaudet AL, Clayton-Smith J, ''et al'' |title=Angelman syndrome 2005: updated consensus for diagnostic criteria |journal=Am. J. Med. Genet. A |volume=140 |issue=5 |pages=413-8 |year=2006 |pmid=16470747 |doi=10.1002/ajmg.a.31074}}</ref>


:* [criterion 1]
:*Developement history. Normal [[birth]], delayed motor [[milestones]], with no loss of [[skills]].<ref name="pmid194551856" /><ref name="pmid22670133" />
:* [criterion 2]
:*[[Clinical]] findings. Clinical features (puppet-like movements, [[Speech and language pathology|speech impairment]], [[feeding]] dificulties, unprovoked [[laughter]], etc.) previously described, [[Dysmorphic feature|dysmorphic facies]], and [[behavioural]] uniqueness.<ref name="pmid194551856" />
:* [criterion 3]
:*[[Genetic testing]]. [[Deletion (genetics)|Deletion]] in [[Chromosome abnormality|chromosomal]] region [[:File:Angelman.PNG|15q11-13]] with absence of [[UBE3A|''UBE3A'' gene]].<ref name="pmid194551856" />
:* [criterion 4]


=== Symptoms ===
===Symptoms===
Angelman syndrome is usually [[Asymptomatic condition|asymptomatic]].


* [Disease name] is usually asymptomatic.
===Physical Examination===
* Symptoms of [disease name] may include the following:


:* [symptom 1]
*Patients with Angelman syndrome usually appear [[Dysmorphic feature|dysmorphic.]]<ref name="pmid19455185">{{cite journal |vauthors=Van Buggenhout G, Fryns JP |title=Angelman syndrome (AS, MIM 105830) |journal=Eur. J. Hum. Genet. |volume=17 |issue=11 |pages=1367–73 |date=November 2009 |pmid=19455185 |pmc=2986680 |doi=10.1038/ejhg.2009.67 |url=}}</ref><ref name="pmid20445456" />
:* [symptom 2]
*The most common [[physical examination]] findings are:<ref name="pmid194551856" />
:* [symptom 3]
:* [symptom 4]
:* [symptom 5]
:* [symptom 6]


=== Physical Examination ===
:*Flat [[occiput]] <ref name="SidorovDeck20172">{{cite journal|last1=Sidorov|first1=Michael S.|last2=Deck|first2=Gina M.|last3=Dolatshahi|first3=Marjan|last4=Thibert|first4=Ronald L.|last5=Bird|first5=Lynne M.|last6=Chu|first6=Catherine J.|last7=Philpot|first7=Benjamin D.|title=Delta rhythmicity is a reliable EEG biomarker in Angelman syndrome: a parallel mouse and human analysis|journal=Journal of Neurodevelopmental Disorders|volume=9|issue=1|year=2017|issn=1866-1947|doi=10.1186/s11689-017-9195-8}}</ref>
 
:*[[Microcephaly|Below average head size]]<ref name="urlAngelman syndrome - Symptoms and causes - Mayo Clinic2">{{cite web |url=https://www.mayoclinic.org/diseases-conditions/angelman-syndrome/symptoms-causes/syc-20355621#:~:text=Developmental%20delays%2C%20which%20begin%20between,2%20and%203%20years%20old. |title=Angelman syndrome - Symptoms and causes - Mayo Clinic |format= |work= |accessdate=}}</ref><ref name="pmid20445456" />
* Patients with Angelman syndrome usually appear dysmorphic.<ref name="pmid19455185">{{cite journal |vauthors=Van Buggenhout G, Fryns JP |title=Angelman syndrome (AS, MIM 105830) |journal=Eur. J. Hum. Genet. |volume=17 |issue=11 |pages=1367–73 |date=November 2009 |pmid=19455185 |pmc=2986680 |doi=10.1038/ejhg.2009.67 |url=}}</ref>
:*[[Occipital groove]]<ref name="SidorovDeck20172" />
* The most common physical examination finding are:
:*Protruding tongue<ref name="SidorovDeck20172" /><ref name="pmid20445456" />
 
:* Flat occiput <ref name="SidorovDeck20172">{{cite journal|last1=Sidorov|first1=Michael S.|last2=Deck|first2=Gina M.|last3=Dolatshahi|first3=Marjan|last4=Thibert|first4=Ronald L.|last5=Bird|first5=Lynne M.|last6=Chu|first6=Catherine J.|last7=Philpot|first7=Benjamin D.|title=Delta rhythmicity is a reliable EEG biomarker in Angelman syndrome: a parallel mouse and human analysis|journal=Journal of Neurodevelopmental Disorders|volume=9|issue=1|year=2017|issn=1866-1947|doi=10.1186/s11689-017-9195-8}}</ref>
:*Small head size<ref name="urlAngelman syndrome - Symptoms and causes - Mayo Clinic2">{{cite web |url=https://www.mayoclinic.org/diseases-conditions/angelman-syndrome/symptoms-causes/syc-20355621#:~:text=Developmental%20delays%2C%20which%20begin%20between,2%20and%203%20years%20old. |title=Angelman syndrome - Symptoms and causes - Mayo Clinic |format= |work= |accessdate=}}</ref>
:*Occipital groove<ref name="SidorovDeck20172" />
:*Protruding tongue<ref name="SidorovDeck20172" />
:*Tongue thrusting<ref name="SidorovDeck20172" />
:*Tongue thrusting<ref name="SidorovDeck20172" />
:*Truncal hypotonia<ref name="SidorovDeck20172" />
:*Truncal hypotonia<ref name="SidorovDeck20172" />
:*Prognathia<ref name="SidorovDeck20172" />
:*[[Prognathia]]<ref name="SidorovDeck20172" />
:*Wide mouth<ref name="SidorovDeck20172" />
:*Wide mouth<ref name="SidorovDeck20172" />
:*Wide spaced teeth<ref name="SidorovDeck20172" />
:*Wide spaced teeth<ref name="SidorovDeck20172" />
:*Strabismus<ref name="SidorovDeck20172" />
:*[[Strabismus]]<ref name="SidorovDeck20172" />
:*Light color of skin,hair, and eyes<ref name="SidorovDeck20172" />
:*Light color of skin,hair, and eyes<ref name="SidorovDeck20172" />
:*Uplifted, flexed arm position during ambulation<ref name="SidorovDeck20172" />
:*Uplifted, flexed arm position during ambulation<ref name="SidorovDeck20172" />
:*Valgus positioned ankles<ref name="SidorovDeck20172" />
:*[[Valgus]] positioned ankles<ref name="SidorovDeck20172" />
:*Obesity found in older child<ref name="SidorovDeck20172" />
:*[[Obesity]] found in older child<ref name="SidorovDeck20172" />
:*Scoliosis<ref name="SidorovDeck20172" />
:*[[Scoliosis]]<ref name="SidorovDeck20172" /><ref name="pmid20445456" />
 
=== Laboratory Findings ===
 
* There are no specific laboratory findings associated with [disease name].
 
* A [positive/negative] [test name] is diagnostic of [disease name].
* An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
* Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].
 
=== Imaging Findings ===
 
* There are no [imaging study] findings associated with [disease name].
 
* [Imaging study 1] is the imaging modality of choice for [disease name].
* On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
* [Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].
 
=== Other Diagnostic Studies ===
 
* [Disease name] may also be diagnosed using [diagnostic study name].
* Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].
 
The diagnosis of Angelman syndrome is based on:
 
* A history of delayed motor milestones and then later a delay in general development, especially of speech
* Unusual movements including fine tremors, jerky limb movements, hand flapping and a wide-based, stiff-legged gait.
* Characteristic facial appearance (but not in all cases).
* A history of epilepsy and an abnormal [[EEG]] tracing.
* A happy disposition with frequent laughter
* A deletion on chromosome 15
 
The Angelman Syndrome Foundation defined criteria for diagnosis in 1995,<ref name="pmid7625452">{{cite journal |author=Williams CA, Angelman H, Clayton-Smith J, ''et al'' |title=Angelman syndrome: consensus for diagnostic criteria. Angelman Syndrome Foundation |journal=Am. J. Med. Genet. |volume=56 |issue=2 |pages=237-8 |year=1995 |pmid=7625452 |doi=10.1002/ajmg.1320560224}}</ref>, and updated these criteria in 2005.<ref name="pmid16470747">{{cite journal |author=Williams CA, Beaudet AL, Clayton-Smith J, ''et al'' |title=Angelman syndrome 2005: updated consensus for diagnostic criteria |journal=Am. J. Med. Genet. A |volume=140 |issue=5 |pages=413-8 |year=2006 |pmid=16470747 |doi=10.1002/ajmg.a.31074}}</ref>
===Diagnostic Criteria===
 
===Features===
* Feeding problems during infancy (poor suck and poor weight gain) in 75%
* Delay in sitting and walking
* Absent or little speech (not in all cases - some children have a vocabulary of up to 50 words)
* Receptive and non-verbal communication skills higher than verbal ones
* Poor attention span and [[hyperactivity]]
* Severe learning disabilities
* [[Epilepsy]] (80%) and an abnormal EEG
* Unusual movements (fine tremors, hand flapping, jerking movements)
* Affectionate nature and frequent laughter
* Wide-based stiff-legged gait, with tendency to hold arms up and flexed while walking.
* Below average head size, often with flattening at the back
* Subtle, but ''sometimes'' characteristic facial features (wide mouth, widely spaced teeth, prominent chin, tendency to tongue thrust)
* Poor sleeping pattern
* [[Strabismus]] (Squint - crossed eye/s) in 40%
* [[Scoliosis]] (abnormal curvature of the spine) in 10%
* Increased sensitivity to heat
* Attraction to/fascination with water
 
===History and Symptoms===
 
===Physical Examination===


===Laboratory Findings===
===Laboratory Findings===


=== EEG ===
* [[Hematologic]], [[metabolic]], and [[chemical]] laboratory findings in Angelman syndrome are usually normal.<ref name="pmid194551856">{{cite journal |vauthors=Van Buggenhout G, Fryns JP |title=Angelman syndrome (AS, MIM 105830) |journal=Eur. J. Hum. Genet. |volume=17 |issue=11 |pages=1367–73 |date=November 2009 |pmid=19455185 |pmc=2986680 |doi=10.1038/ejhg.2009.67 |url=}}</ref>
The most common patern observed in Angelman syndrome are signals of high amplitude rhythmic 2–3 Hz activity (delta rythmicity) primarly over the frontal regions with superimposed interictal epileptiform discharges.<ref name="LaanVein2005">{{cite journal|last1=Laan|first1=Laura A.E.M.|last2=Vein|first2=Alla A.|title=Angelman syndrome: is there a characteristic EEG?|journal=Brain and Development|volume=27|issue=2|year=2005|pages=80–87|issn=03877604|doi=10.1016/j.braindev.2003.09.013}}</ref> Other patern found are rhythmic theta, and epileptiform spike-wave discharges.<ref name="SidorovDeck2017">{{cite journal|last1=Sidorov|first1=Michael S.|last2=Deck|first2=Gina M.|last3=Dolatshahi|first3=Marjan|last4=Thibert|first4=Ronald L.|last5=Bird|first5=Lynne M.|last6=Chu|first6=Catherine J.|last7=Philpot|first7=Benjamin D.|title=Delta rhythmicity is a reliable EEG biomarker in Angelman syndrome: a parallel mouse and human analysis|journal=Journal of Neurodevelopmental Disorders|volume=9|issue=1|year=2017|issn=1866-1947|doi=10.1186/s11689-017-9195-8}}</ref>


===Imaging Findings===
===Imaging Findings===


===Other Diagnostic Studies===
* Usually, [[MRI]] and [[Computed tomography|CT scans]] demonstrate normal structural finidings; in some cases, there may be cortical [[atrophy]] or [[Demyelinating|demyelinating lesions]].<ref name="pmid194551856" />


==Treatment==
===EEG===
=== Medical Therapy ===


* There is no treatment for [disease name]; the mainstay of therapy is supportive care.
* The most common [[EEG]] patern observed in Angelman syndrome are signals of high amplitude rhythmic 2–3 Hz activity ([[delta rythmicity]]) primarly over the frontal regions with superimposed [[Interictal|interictal epileptiform]] discharges.<ref name="LaanVein2005">{{cite journal|last1=Laan|first1=Laura A.E.M.|last2=Vein|first2=Alla A.|title=Angelman syndrome: is there a characteristic EEG?|journal=Brain and Development|volume=27|issue=2|year=2005|pages=80–87|issn=03877604|doi=10.1016/j.braindev.2003.09.013}}</ref> Other patern found are rhythmic [[Theta rhythm|theta]], and epileptiform spike-wave discharges.<ref name="SidorovDeck2017">{{cite journal|last1=Sidorov|first1=Michael S.|last2=Deck|first2=Gina M.|last3=Dolatshahi|first3=Marjan|last4=Thibert|first4=Ronald L.|last5=Bird|first5=Lynne M.|last6=Chu|first6=Catherine J.|last7=Philpot|first7=Benjamin D.|title=Delta rhythmicity is a reliable EEG biomarker in Angelman syndrome: a parallel mouse and human analysis|journal=Journal of Neurodevelopmental Disorders|volume=9|issue=1|year=2017|issn=1866-1947|doi=10.1186/s11689-017-9195-8}}</ref>


* The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
==Treatment==
* [Medical therapy 1] acts by [mechanism of action 1].
===Medical Therapy===
* Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].


=== Surgery ===
*Currently, there is no specific treatment for Angelman syndrome.<ref name="pmid26040994">{{cite journal |vauthors=Margolis SS, Sell GL, Zbinden MA, Bird LM |title=Angelman Syndrome |journal=Neurotherapeutics |volume=12 |issue=3 |pages=641–50 |date=July 2015 |pmid=26040994 |pmc=4489961 |doi=10.1007/s13311-015-0361-y |url=}}</ref>
*Treatment is only supportive and is amied to:<ref name="pmid26040994" /><ref name="pmid24876791">{{cite journal |vauthors=Bird LM |title=Angelman syndrome: review of clinical and molecular aspects |journal=Appl Clin Genet |volume=7 |issue= |pages=93–104 |date=2014 |pmid=24876791 |pmc=4036146 |doi=10.2147/TACG.S57386 |url=}}</ref>
*#Mitigate gross and fine motor delays.<ref name="pmid26040994" /><ref name="pmid24876791" /><ref name="pmid22670133" /><ref name="pmid20445456" />
*#Improve [[Communication disorder|communication]] with non-verbal methods (eg. use of communication devices, implement a [[Sign language media|sign language]], exchange of image cards).<ref name="pmid26040994" /><ref name="pmid24876791" /><ref name="pmid22670133" /><ref name="pmid20445456" />
*#Intervention for [[autism spectrum disorder]], when present.<ref name="pmid26040994" /><ref name="pmid24876791" /><ref name="pmid22670133" /><ref name="pmid20445456" />


* Surgery is the mainstay of therapy for [disease name].
*[[Feeding]] in newborns may requiere special [[Nipple|nipples]] due to poor [[Suction|sucking]].<ref name="pmid20445456" /><ref name="pmid203013236" />
* [Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
*[[Anticonvulsant|Antiepileptics]] are used for [[Seizure|seizures]], but there hasn't been a consensus on wich medication is the most appropiate.<ref name="pmid20445456" /><ref name="pmid19453717">{{cite journal |vauthors=Thibert RL, Conant KD, Braun EK, Bruno P, Said RR, Nespeca MP, Thiele EA |title=Epilepsy in Angelman syndrome: a questionnaire-based assessment of the natural history and current treatment options |journal=Epilepsia |volume=50 |issue=11 |pages=2369–76 |date=November 2009 |pmid=19453717 |doi=10.1111/j.1528-1167.2009.02108.x |url=}}</ref><ref name="pmid203013236" />
* [Surgical procedure] can only be performed for patients with [disease stage] [disease name].
*[[Stimulant|Stimulants]] ([[methylphenidate]]) have been used to control [[Attention-deficit hyperactivity disorder|hyperactivity behaviours]].<ref name="pmid20445456" /><ref name="pmid26040994" />
*[[Physiotherapy]] may improve [[range of movements]] and prevents [[joint stiffness]].
*[[Occupational therapy]] helps to ameliorate [[Fine motor skill|fine motor]] and [[oral-motor]] control.<ref name="pmid20445456" /><ref name="pmid203013236" />
*Use of low-potency [[Sedative|sedatives]] may help with disruptive [[nighttime wakefulness]].<ref name="pmid20445456" /><ref name="pmid10392349">{{cite journal |vauthors=Zhdanova IV, Wurtman RJ, Wagstaff J |title=Effects of a low dose of melatonin on sleep in children with Angelman syndrome |journal=J. Pediatr. Endocrinol. Metab. |volume=12 |issue=1 |pages=57–67 |date=1999 |pmid=10392349 |doi=10.1515/jpem.1999.12.1.57 |url=}}</ref><ref name="pmid26040994" />
*[[Orthopedic|Orthopedic postures]] may be corrected with [[Brace (orthopaedic)|bracing]].<ref name="pmid20445456" /><ref name="pmid203013236" />
*[[Dietary recomendations]] should be made in patients with [[constipation]] and/or [[obesity]].<ref name="pmid11748306">{{cite journal |vauthors=Lossie AC, Whitney MM, Amidon D, Dong HJ, Chen P, Theriaque D, Hutson A, Nicholls RD, Zori RT, Williams CA, Driscoll DJ |title=Distinct phenotypes distinguish the molecular classes of Angelman syndrome |journal=J. Med. Genet. |volume=38 |issue=12 |pages=834–45 |date=December 2001 |pmid=11748306 |pmc=1734773 |doi=10.1136/jmg.38.12.834 |url=}}</ref><ref name="pmid26040994" />


=== Prevention ===
===Surgery===


* There are no primary preventive measures available for [disease name].
*Sometimes [[fundoplication]] may be requiered for [[Reflux esophagitis|reflux symptoms]].<ref name="pmid20445456" />
*[[Orthopedic surgery|Surgery]] may be needed to correct certain orthopedic problems (eg. severe [[scoliosis]]).<ref name="pmid20445456" /><ref name="pmid203013236">{{cite journal |vauthors=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, Dagli AI, Mueller J, Williams CA |title= |journal= |volume= |issue= |pages= |date= |pmid=20301323 |doi= |url=}}</ref>
*Surgery for [[tongue protrusion]] has not found to be effective.<ref name="pmid20445456" />


* Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
===Prevention===


* Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
* There are no primary [[Preventive care|preventive]] measures available for Angelman syndrome.
 
Because Angelman syndrome is not an illness, but a genetic condition, there is no currently available cure for AS. The epilepsy can be controlled by the use of one or more types of anticonvulsant medications. However, there are difficulties in ascertaining the levels and types of anticonvulsant medications needed to establish control, because AS is usually associated with having multiple varieties of seizures, rather than just the one as is normal cases of epilepsy. Many families use melatonin to promote sleep in a condition which often affects sleep patterns. Many individuals with Angelman Syndrome sleep for a maximum of 5 hours at any one time. Mild laxatives are also used frequently to encourage regular bowel movements and early intervention with [[physiotherapy]] is important to encourage joint mobility and prevent stiffening of the joints. [[Occupational therapy]], [[speech therapy]], [[hydrotherapy]] and [[music therapy]] are also used in the management of this condition.
===Medical Therapy===
 
===Surgery===
 
===Prevention===


==Living with Angelman syndrome==
==Living with Angelman syndrome==
Although a diagnosis of AS is life changing, it does not need to be life destroying. Individuals with Angelman Syndrome are generally happy and contented individuals, who like human contact and play. AS individuals exhibit a profound desire for personal interaction with others. Communication can be difficult at first, but as an AS child develops, there is a definite character and ability to make themselves understood. It is widely accepted that their understanding of communication directed to them is much larger than their ability to return conversation. Most afflicted individuals will not develop more than 5-10 words, if at all.<ref name="pmid11432411">{{cite journal |author=Andersen WH, Rasmussen RK, Strømme P |title=Levels of cognitive and linguistic development in Angelman syndrome: a study of 20 children |journal=Logopedics, phoniatrics, vocology |volume=26 |issue=1 |pages=2-9 |year=2001 |pmid=11432411 |doi=}}</ref>
Although a diagnosis of Angelman syndrome is life-changing, it does not need to be life-destroying. Individuals with Angelman Syndrome are generally happy and contented individuals, who like human contact and play. Angelman syndrome individuals exhibit a profound desire for personal interaction with others. [[Communication disorder|Communication]] can be difficult at first, but as an AS child develops, there is a definite character and ability to make themselves understood. It is widely accepted that their understanding of communication directed to them is much larger than their ability to return conversation.<ref name="pmid11432411">{{cite journal |author=Andersen WH, Rasmussen RK, Strømme P |title=Levels of cognitive and linguistic development in Angelman syndrome: a study of 20 children |journal=Logopedics, phoniatrics, vocology |volume=26 |issue=1 |pages=2-9 |year=2001 |pmid=11432411 |doi=}}</ref>


==See also==
==See also==
* [[Epigenetics]]
 
*[[Epigenetics]]


==External links==
==External links==
*{{dmoz|Health/Conditions_and_Diseases/Neurological_Disorders/Movement_Disorders/Angelman_Syndrome|Angelman syndrome}}  
 
*{{dmoz|Health/Conditions_and_Diseases/Neurological_Disorders/Movement_Disorders/Angelman_Syndrome|Angelman syndrome}}
*{{GeneTests|angelman|Angelman Syndrome}}
*{{GeneTests|angelman|Angelman Syndrome}}
*[http://www.angelman.org Angelman Syndrome Foundation USA]
*[http://www.angelman.org Angelman Syndrome Foundation USA]

Latest revision as of 17:29, 4 September 2020

WikiDoc Resources for Angelman syndrome

Articles

Most recent articles on Angelman syndrome

Most cited articles on Angelman syndrome

Review articles on Angelman syndrome

Articles on Angelman syndrome in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Angelman syndrome

Images of Angelman syndrome

Photos of Angelman syndrome

Podcasts & MP3s on Angelman syndrome

Videos on Angelman syndrome

Evidence Based Medicine

Cochrane Collaboration on Angelman syndrome

Bandolier on Angelman syndrome

TRIP on Angelman syndrome

Clinical Trials

Ongoing Trials on Angelman syndrome at Clinical Trials.gov

Trial results on Angelman syndrome

Clinical Trials on Angelman syndrome at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Angelman syndrome

NICE Guidance on Angelman syndrome

NHS PRODIGY Guidance

FDA on Angelman syndrome

CDC on Angelman syndrome

Books

Books on Angelman syndrome

News

Angelman syndrome in the news

Be alerted to news on Angelman syndrome

News trends on Angelman syndrome

Commentary

Blogs on Angelman syndrome

Definitions

Definitions of Angelman syndrome

Patient Resources / Community

Patient resources on Angelman syndrome

Discussion groups on Angelman syndrome

Patient Handouts on Angelman syndrome

Directions to Hospitals Treating Angelman syndrome

Risk calculators and risk factors for Angelman syndrome

Healthcare Provider Resources

Symptoms of Angelman syndrome

Causes & Risk Factors for Angelman syndrome

Diagnostic studies for Angelman syndrome

Treatment of Angelman syndrome

Continuing Medical Education (CME)

CME Programs on Angelman syndrome

International

Angelman syndrome en Espanol

Angelman syndrome en Francais

Business

Angelman syndrome in the Marketplace

Patents on Angelman syndrome

Experimental / Informatics

List of terms related to Angelman syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Moises Romo, M.D.

Angelman Syndrome
ICD-10 Q93.5
ICD-9 759.89
OMIM 105830
DiseasesDB 712
MeSH D017204

Overview

Angelman syndrome, formerly known as "happy puppet syndrome", is a genetic disorder characterized by intelectual and development delay, seizures, puppet-like movement, unprovoked laughter/smiling, and excessive socialization with strangers.


Historical Perspective

"I happened to see an oil painting...called... "a Boy with a Puppet". The boy's laughing face and the fact that my patients exhibited jerky movements gave me the idea of writing an article about the three children with a title of Puppet Children."[1]


Pathophysiology

Modes of Inheritance

Phenotype-Gene Relationships

Phenotype Gene Location
Angelman syndrome UBE3A 15q11-15q13


Clinical Features

Angelman syndrome is characterized by:

Other less common features are:


Differentiating Angelman syndrome from Other Diseases

Angelman syndrome must be differentiated from other diseases that cause intelectual and development delay, dysmorphic facies, and seizures, such as:

Diseases Type of motor abnormality Clinical findings Laboratory findings and diagnostic tests Radiographic findings
Spasticity Hypotonia Ataxia Dystonia
Leigh syndrome - - + +
Niemann-Pick disease type C - - + +
  • Abnormal liver function tests
  • Fibroblast cell culture with filipin staining
Infantile Refsum disease - + + - Elevated plasma VLCFA levels --
Adrenoleukodystrophy + - - -
  • Elevated plasma VLCFA levels
  • Molecular genetic testing for mutations in the ABCD1 gene
 --
Zellweger syndrome - + - - --
Pyruvate dehydrogenase deficiency + + + -
  • Elevated lactate and pyruvate levels in blood and CSF
  • Abnormal PDH enzymatic activity in cultured fibroblasts
 --
Arginase deficiency + - - - --
Holocarboxylase synthetase deficiency - + - - Elevated levels of:
  • Beta-hydroxyisovalerate
  • Beta-methylcrotonylglycine
  • Beta-hydroxypropionate
  • Methylcitrate
  • Tiglylglycine
 --
Glutaric aciduria type 1 - - - + Elevated levels of:
Ataxia telangiectasia - - + - --
Pontocerebellar hypoplasias - + - - Genetic testing for PCH gene mutations
Metachromatic leukodystrophy - + + -
  • Deficient arylsulfatase A enzyme activity in leukocytes or cultured skin fibroblasts
 --
Pelizaeus-Merzbacher + - + -
Angelman syndrome - - + -
  • Methylation studies and chromosome microarray to detect chromosome 15 anomalies and UBE3A mutations
 --
Rett syndrome + - - +
  • Occurs almost exclusively in females
  • Normal development during first six months followed by regression and loss of milestones
  • Loss of speech capability
  • Stereotypic hand movements
  • Seizures
  • Autistic features
  • Clinical diagnosis
  • Genetic testing for MECP2 mutations
 --
Lesch-Nyhan syndrome + - - + --
Miller-Dieker lissencephaly + + - -
  • Cytogenetic testing for 17p13.3 microdeletion
 --
Dopa-responsive dystonia + - - +
  • Onset in early childhood
  • Symptoms worsen with fatigue and exercise
  • Positive response to a trial of levodopa
 --


Epidemiology and Demographics

  • The prevalence of Angelman syndrome is approximately 5-7 per 100,000 individuals worldwide.[18]
  • The exact incidence of Angelman syndrome is unknown, but its estimated to be between 6-7 per 100,000 births .[19]

Age

Full spectrum of the disease appears usually before 3 years of age.[20]

Gender

Angelman syndrome affects men and women equally.[18][21]

Race

There is no racial predilection for Angelman syndrome.[22]

Risk Factors

There are no risk factors for developing Angelman syndrome, since most of the cases occur due to a de novo deletion and there is a very small chance for this condition to be hereditary transmitted.[23]

Screening

Prenatal screening of 15q11.2-q13 region mutations is possible through DNA and/or chromosomal/FISH analysis of fetal cells acquired by chorionic villus sampling or amniocentesis.[15]

Screening for Angelman syndrome-suspected patients can be made by the following tests:


Natural History, Complications & Prognosis


Diagnosis

Diagnostic Criteria

The Angelman Syndrome Foundation defined criteria for diagnosis in 1995, and updated his criteria in 2006.[33]

The diagnosis of Angelman syndrome according to the Scientific Advisory Committee of the US Angelman syndrome Foundation (Williams et al 2006) is based on:[34][35][36]

Symptoms

Angelman syndrome is usually asymptomatic.

Physical Examination

Laboratory Findings

Imaging Findings

EEG

  • The most common EEG patern observed in Angelman syndrome are signals of high amplitude rhythmic 2–3 Hz activity (delta rythmicity) primarly over the frontal regions with superimposed interictal epileptiform discharges.[39] Other patern found are rhythmic theta, and epileptiform spike-wave discharges.[40]

Treatment

Medical Therapy

Surgery

Prevention

  • There are no primary preventive measures available for Angelman syndrome.

Living with Angelman syndrome

Although a diagnosis of Angelman syndrome is life-changing, it does not need to be life-destroying. Individuals with Angelman Syndrome are generally happy and contented individuals, who like human contact and play. Angelman syndrome individuals exhibit a profound desire for personal interaction with others. Communication can be difficult at first, but as an AS child develops, there is a definite character and ability to make themselves understood. It is widely accepted that their understanding of communication directed to them is much larger than their ability to return conversation.[30]

See also

External links

References

  1. ↑ 1.0 1.1 Template:WhoNamedIt
  2. ↑ Angelman, Harry (2008). "'Puppet' Children A Report on Three Cases". Developmental Medicine & Child Neurology. 7 (6): 681–688. doi:10.1111/j.1469-8749.1965.tb07844.x. ISSN 0012-1622.
  3. ↑ 3.0 3.1 Jana NR (2012). "Understanding the pathogenesis of Angelman syndrome through animal models". Neural Plast. 2012: 710943. doi:10.1155/2012/710943. PMC 3399338. PMID 22830052.
  4. ↑ Malzac P, Webber H, Moncla A, Graham JM, Kukolich M, Williams C, Pagon RA, Ramsdell LA, Kishino T, Wagstaff J (June 1998). "Mutation analysis of UBE3A in Angelman syndrome patients". Am. J. Hum. Genet. 62 (6): 1353–60. doi:10.1086/301877. PMC 1377156. PMID 9585605.
  5. ↑ Clayton-Smith, J; Pembrey, M E (1992). "Angelman syndrome". Journal of Medical Genetics. 29 (6): 412–415. doi:10.1136/jmg.29.6.412. ISSN 1468-6244.
  6. ↑ Van Buggenhout G, Fryns JP (November 2009). "Angelman syndrome (AS, MIM 105830)". Eur. J. Hum. Genet. 17 (11): 1367–73. doi:10.1038/ejhg.2009.67. PMC 2986680. PMID 19455185.
  7. ↑ 7.00 7.01 7.02 7.03 7.04 7.05 7.06 7.07 7.08 7.09 7.10 7.11 7.12 7.13
  8. ↑ Tan WH, Bird LM (December 2016). "Angelman syndrome: Current and emerging therapies in 2016". Am J Med Genet C Semin Med Genet. 172 (4): 384–401. doi:10.1002/ajmg.c.31536. PMID 27860204.
  9. ↑ Weeber E, Levenson J, Sweatt J (2002). "Molecular genetics of human cognition". Mol Interv. 2 (6): 376–91, 339. PMID 14993414.
  10. ↑ 10.0 10.1 Williams, Charles. "Angelman Syndrome". National Organization of Rare Diseases. Retrieved 06/02/2020. Check date values in: |access-date= (help)
  11. ↑ Van Buggenhout G, Fryns JP (November 2009). "Angelman syndrome (AS, MIM 105830)". Eur. J. Hum. Genet. 17 (11): 1367–73. doi:10.1038/ejhg.2009.67. PMC 2986680. PMID 19455185.
  12. ↑ Van Buggenhout G, Fryns JP (November 2009). "Angelman syndrome (AS, MIM 105830)". Eur. J. Hum. Genet. 17 (11): 1367–73. doi:10.1038/ejhg.2009.67. PMC 2986680. PMID 19455185.
  13. ↑ 13.0 13.1 13.2 13.3 13.4 Jenkins, Brian (2016). Deletion Syndromes/ Step up to USMLE step 2CK. Fort Worth, Texas: Wolters Kluwer. p. 291. ISBN 978-1496309747.
  14. ↑ 14.0 14.1 14.2 14.3 Guerrini R, Carrozzo R, Rinaldi R, Bonanni P (2003). "Angelman syndrome: etiology, clinical features, diagnosis, and management of symptoms". Paediatr Drugs. 5 (10): 647–61. doi:10.2165/00148581-200305100-00001. PMID 14510623.
  15. ↑ 15.00 15.01 15.02 15.03 15.04 15.05 15.06 15.07 15.08 15.09 15.10 15.11 15.12 15.13 15.14 15.15 15.16 15.17 15.18 15.19 15.20 15.21
  16. ↑ Van Buggenhout G, Fryns JP (November 2009). "Angelman syndrome (AS, MIM 105830)". Eur. J. Hum. Genet. 17 (11): 1367–73. doi:10.1038/ejhg.2009.67. PMC 2986680. PMID 19455185.
  17. ↑ 17.00 17.01 17.02 17.03 17.04 17.05 17.06 17.07 17.08 17.09 17.10 17.11 17.12 17.13 17.14 17.15 17.16 17.17 17.18 17.19 17.20 17.21 17.22 17.23 17.24 17.25 Sidorov, Michael S.; Deck, Gina M.; Dolatshahi, Marjan; Thibert, Ronald L.; Bird, Lynne M.; Chu, Catherine J.; Philpot, Benjamin D. (2017). "Delta rhythmicity is a reliable EEG biomarker in Angelman syndrome: a parallel mouse and human analysis". Journal of Neurodevelopmental Disorders. 9 (1). doi:10.1186/s11689-017-9195-8. ISSN 1866-1947.
  18. ↑ 18.0 18.1 Clayton-Smith, J; Pembrey, M E (1992). "Angelman syndrome". Journal of Medical Genetics. 29 (6): 412–415. doi:10.1136/jmg.29.6.412. ISSN 1468-6244.
  19. ↑ "www.angelman.org" (PDF).
  20. ↑ "Angelman syndrome - Symptoms and causes - Mayo Clinic".
  21. ↑ Luk HM (2016). "Angelman-Like Syndrome: A Genetic Approach to Diagnosis with Illustrative Cases". Case Rep Genet. 2016: 9790169. doi:10.1155/2016/9790169. PMC 4749774. PMID 26942024.
  22. ↑
  23. ↑ Guerrini R, Carrozzo R, Rinaldi R, Bonanni P (2003). "Angelman syndrome: etiology, clinical features, diagnosis, and management of symptoms". Paediatr Drugs. 5 (10): 647–61. doi:10.2165/00148581-200305100-00001. PMID 14510623.
  24. ↑ 24.0 24.1 24.2 24.3 24.4 24.5 Guerrini R, Carrozzo R, Rinaldi R, Bonanni P (2003). "Angelman syndrome: etiology, clinical features, diagnosis, and management of symptoms". Paediatr Drugs. 5 (10): 647–61. doi:10.2165/00148581-200305100-00001. PMID 14510623.
  25. ↑ 25.0 25.1 25.2 25.3 25.4 25.5 "www.ncbi.nlm.nih.gov" (PDF).
  26. ↑ 26.0 26.1 Laan LA, den Boer AT, Hennekam RC, Renier WO, Brouwer OF (1996). "Angelman syndrome in adulthood". Am. J. Med. Genet. 66 (3): 356–60. doi:10.1002/(SICI)1096-8628(19961218)66:3%3C356::AID-AJMG21%3E3.0.CO;2-K. PMID 9072912.
  27. ↑ Laan LA, den Boer AT, Hennekam RC, Renier WO, Brouwer OF (December 1996). "Angelman syndrome in adulthood". Am. J. Med. Genet. 66 (3): 356–60. doi:10.1002/(SICI)1096-8628(19961218)66:3<356::AID-AJMG21>3.0.CO;2-K. PMID 9072912.
  28. ↑ Lossie A, Driscoll D. "Transmission of Angelman syndrome by an affected mother". Genet Med. 1 (6): 262–6. PMID 11258627.
  29. ↑ Lossie AC, Driscoll DJ (1999). "Transmission of Angelman syndrome by an affected mother". Genet. Med. 1 (6): 262–6. doi:10.1097/00125817-199909000-00004. PMID 11258627.
  30. ↑ 30.0 30.1 Andersen WH, Rasmussen RK, Strømme P (2001). "Levels of cognitive and linguistic development in Angelman syndrome: a study of 20 children". Logopedics, phoniatrics, vocology. 26 (1): 2–9. PMID 11432411.
  31. ↑ 31.0 31.1 Bonello D, Camilleri F, Calleja-Agius J (May 2017). "Angelman Syndrome: Identification and Management". Neonatal Netw. 36 (3): 142–151. doi:10.1891/0730-0832.36.3.142. PMID 28494826.
  32. ↑ Herbst, Jonathon; Byard, Roger W. (2012). "Sudden Death and Angelman Syndrome". Journal of Forensic Sciences. 57 (1): 257–259. doi:10.1111/j.1556-4029.2011.01901.x. ISSN 0022-1198.
  33. ↑ Williams CA, Angelman H, Clayton-Smith J; et al. (1995). "Angelman syndrome: consensus for diagnostic criteria. Angelman Syndrome Foundation". Am. J. Med. Genet. 56 (2): 237–8. doi:10.1002/ajmg.1320560224. PMID 7625452.
  34. ↑ Williams CA, Beaudet AL, Clayton-Smith J, Knoll JH, Kyllerman M, Laan LA, Magenis RE, Moncla A, Schinzel AA, Summers JA, Wagstaff J (March 2006). "Angelman syndrome 2005: updated consensus for diagnostic criteria". Am. J. Med. Genet. A. 140 (5): 413–8. doi:10.1002/ajmg.a.31074. PMID 16470747.
  35. ↑ 35.0 35.1 35.2 35.3 35.4 35.5 35.6 Van Buggenhout G, Fryns JP (November 2009). "Angelman syndrome (AS, MIM 105830)". Eur. J. Hum. Genet. 17 (11): 1367–73. doi:10.1038/ejhg.2009.67. PMC 2986680. PMID 19455185.
  36. ↑ Williams CA, Beaudet AL, Clayton-Smith J; et al. (2006). "Angelman syndrome 2005: updated consensus for diagnostic criteria". Am. J. Med. Genet. A. 140 (5): 413–8. doi:10.1002/ajmg.a.31074. PMID 16470747.
  37. ↑ Van Buggenhout G, Fryns JP (November 2009). "Angelman syndrome (AS, MIM 105830)". Eur. J. Hum. Genet. 17 (11): 1367–73. doi:10.1038/ejhg.2009.67. PMC 2986680. PMID 19455185.
  38. ↑ "Angelman syndrome - Symptoms and causes - Mayo Clinic".
  39. ↑ Laan, Laura A.E.M.; Vein, Alla A. (2005). "Angelman syndrome: is there a characteristic EEG?". Brain and Development. 27 (2): 80–87. doi:10.1016/j.braindev.2003.09.013. ISSN 0387-7604.
  40. ↑ Sidorov, Michael S.; Deck, Gina M.; Dolatshahi, Marjan; Thibert, Ronald L.; Bird, Lynne M.; Chu, Catherine J.; Philpot, Benjamin D. (2017). "Delta rhythmicity is a reliable EEG biomarker in Angelman syndrome: a parallel mouse and human analysis". Journal of Neurodevelopmental Disorders. 9 (1). doi:10.1186/s11689-017-9195-8. ISSN 1866-1947.
  41. ↑ 41.0 41.1 41.2 41.3 41.4 41.5 41.6 41.7 Margolis SS, Sell GL, Zbinden MA, Bird LM (July 2015). "Angelman Syndrome". Neurotherapeutics. 12 (3): 641–50. doi:10.1007/s13311-015-0361-y. PMC 4489961. PMID 26040994.
  42. ↑ 42.0 42.1 42.2 42.3 Bird LM (2014). "Angelman syndrome: review of clinical and molecular aspects". Appl Clin Genet. 7: 93–104. doi:10.2147/TACG.S57386. PMC 4036146. PMID 24876791.
  43. ↑ 43.0 43.1 43.2 43.3 43.4 Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean L, Stephens K, Amemiya A, Dagli AI, Mueller J, Williams CA. PMID 20301323. Vancouver style error: initials (help); Missing or empty |title= (help)
  44. ↑ Thibert RL, Conant KD, Braun EK, Bruno P, Said RR, Nespeca MP, Thiele EA (November 2009). "Epilepsy in Angelman syndrome: a questionnaire-based assessment of the natural history and current treatment options". Epilepsia. 50 (11): 2369–76. doi:10.1111/j.1528-1167.2009.02108.x. PMID 19453717.
  45. ↑ Zhdanova IV, Wurtman RJ, Wagstaff J (1999). "Effects of a low dose of melatonin on sleep in children with Angelman syndrome". J. Pediatr. Endocrinol. Metab. 12 (1): 57–67. doi:10.1515/jpem.1999.12.1.57. PMID 10392349.
  46. ↑ Lossie AC, Whitney MM, Amidon D, Dong HJ, Chen P, Theriaque D, Hutson A, Nicholls RD, Zori RT, Williams CA, Driscoll DJ (December 2001). "Distinct phenotypes distinguish the molecular classes of Angelman syndrome". J. Med. Genet. 38 (12): 834–45. doi:10.1136/jmg.38.12.834. PMC 1734773. PMID 11748306.

Template:Chromosomal abnormalities

ca:Síndrome d'Angelman de:Angelman-Syndrom zh-classical:天使人症候群 he:תסמונת אנגלמן hu:Angelman-szindróma nl:Syndroom van Angelman sr:Ангелманов синдром fi:Angelmanin oireyhtymä sv:Angelmans syndrom


Template:WikiDoc Sources

Retrieved from "https://www.wikidoc.org/index.php?title=Angelman_syndrome&oldid=1659375"