Angelman syndrome

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

	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.

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

Angelman syndrome was first discovered by Dr. Harry Angelman, a British pediatrician, in 1965 during his seminar, where he described three children with the typical facies of the syndrome.^[1]^[2]
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."^[1]

In 1987, maternal allele deletion in chromosome 15 was first identified in the pathogenesis of Angelman syndrome.^[3]
In 1994 point mutations in UBE3A gene was known to be the gene responsible for Angelman syndrome.^[3]^[4]

Pathophysiology

Modes of Inheritance

In 70% of the cases, Angelman syndrome is caused by a sporadic (de novo) maternal deletion in chromosomal region 15q11-13 causing an absence of UBE3A gene, involving the ubiquitin pathway.^[5]^[6]^[7] There is a lack of expression of the maternally-inherited UBE3A gene in the brain, while the paternally-inherited copy of UBE3A is silenced.^[8]
Other causes include paternal uniparental disomy, impringting error, translocation, or single gene mutation in UBE3A.^[9]^[7]
3-5% of cases of Angelman syndrome can be inherited.^[10]^[11]
Recurrence of Angelman syndrome in subsequent children when having a child with a de novo deletion is estimated around 1%.^[12]
In approximately 10% of cases, no cause can be identified.^[10]

Phenotype-Gene Relationships

Phenotype	Gene	Location
Angelman syndrome	UBE3A	15q11-15q13

Clinical Features

Angelman syndrome is characterized by:

Puppet-like movement^[13]^[14]^[7]^[15]
Intelectual and development delay^[13]^[16]^[7]^[15]
Seizures^[13]^[7]^[15]
Unprovoked laughter/smiling^[13]^[14]
Excessive socialization with strangers^[13]
Speech impairment^[14]^[7]^[15]

Other less common features are:

Delayed head circumference growth^[17]

Suck/swallowing disorders^[17]^[15]
Feeding problems^[17]
Frequent drooling^[17]
Excessive chewing^[17]
Wide based gait^[17]^[14]
Increased sensitivity to heat^[17]
Diminished need for sleep^[17]
Hydrophilia^[17]
Fascination with crinkly things^[17]
Abnormal feeding conducts^[17]
Constipation^[17]

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
Diseases	Spasticity	Hypotonia	Ataxia	Dystonia	Clinical findings	Laboratory findings and diagnostic tests	Radiographic findings
Leigh syndrome	-	-	+	+	Progressive psychomotor regression Seizures External ophthalmoplegia Lactic acidosis Vomiting	Increased lactate levels in blood and CSF Genetic testing	MRI: abnormal white matter signal in the putamen, basal ganglia, and brainstem on T2 images
Niemann-Pick disease type C	-	-	+	+	Progressive neurodegeneration Hepatosplenomegaly Systemic involvement of liver, spleen, or lung preceedes neurologic symptoms	Abnormal liver function tests Fibroblast cell culture with filipin staining	MRI: Cerebral and cerebellar atrophy Thinning of the corpus callosum
Infantile Refsum disease	-	+	+	-	Abnormalities of the optic nerve and disc Retinitis pigmentosa Sensorineural hearing loss Hepatomegaly and cirrhosis Neurologic deterioration is slower than in Zellweger syndrome or ALD	Elevated plasma VLCFA levels	--
Adrenoleukodystrophy	+	-	-	-	Cognitive and behavioral abnormalities Adrenal insufficiency Hyperpigmented skin Gonadal dysfunction Neurologic deterioration progresses at a variable rate	Elevated plasma VLCFA levels Molecular genetic testing for mutations in the ABCD1 gene	--
Zellweger syndrome	-	+	-	-	Craniofacial dysmorphism Hepatomegaly Neonatal seizures Profound developmental delay MRI findings include cortical and white matter abnormalities Neurologic deterioration is rapid and infants rarely survive beyond six months of age	Elevated plasma VLCFA levels Elevated levels of phytanic acid, pristanic acid, and pipecolic acid in plasma and fibroblasts Reduced plasmalogen in erythrocytes Molecular genetic testing for mutations in the PEX1 or PEX6 genes	--
Pyruvate dehydrogenase deficiency	+	+	+	-	Lactic acidosis Seizures Intellectual disability	Elevated lactate and pyruvate levels in blood and CSF Abnormal PDH enzymatic activity in cultured fibroblasts	--
Arginase deficiency	+	-	-	-	Hyperammonemia Encephalopathy Respiratory alkalosis	Elevated ammonia level Elevated arginine level	--
Holocarboxylase synthetase deficiency	-	+	-	-	Ketoacidosis Dermatitis Alopecia Seizures Developmental delay	Elevated levels of: Beta-hydroxyisovalerate Beta-methylcrotonylglycine Beta-hydroxypropionate Methylcitrate Tiglylglycine	--
Glutaric aciduria type 1	-	-	-	+	Episodes of metabolic decompensation and encephalopathy often precipitated by infection and fever Rarely presents in the newborn period Microencephalic macrocephaly Seizures (approximately 20 percent) Cognitive function is preserved	Elevated levels of: glutaric acid 3-hydroxyglutaric acid	MRI: Frontal and temporal atrophy
Ataxia telangiectasia	-	-	+	-	Progressive cerebellar ataxia Abnormal eye movements Oculocutaneous telangiectasias Immune deficiency Increased risk of malignancy	Elevated serum alpha-fetoprotein level Low IgA and IgG levels Lymphopenia Genetic testing for mutation in the ATM gene	--
Pontocerebellar hypoplasias	-	+	-	-	Progressive muscle atrophy Microcephaly Developmental delay	Genetic testing for PCH gene mutations	MRI : Small cerebellum and brainstem including the pons
Metachromatic leukodystrophy	-	+	+	-	Regression of motor skills Seizures Optic atrophy Reduced or absent deep tendon reflexes Intellectual disability	Deficient arylsulfatase A enzyme activity in leukocytes or cultured skin fibroblasts	--
Pelizaeus-Merzbacher	+	-	+	-	Nystagmus Cognitive impairment Onset in infancy Slowly progressive Language development may be normal	Genetic testing for mutations in PLP1 gene	MRI: White matter abnormalities
Angelman syndrome	-	-	+	-	Profound intellectual disability Postnatal microcephaly Typical abnormal behaviors (paroxysmal laughter, easily excitable)	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	+	-	-	+	Self-mutilating behavior Urinary stones due to hyperuricemia	Elevated uric acid level Abnormal enzymatic activity of HPRT in cultured fibroblasts Genetic testing for HPRT gene mutations	--
Miller-Dieker lissencephaly	+	+	-	-	Lissencephaly Microcephaly Dysmorphic features Seizures Failure to thrive	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:

Karyotyping. Is warranted for any patient with suspected Angelman syndrome.^[24]
Fluorescent in situ hybridization (FISH). May detect deletions, but not imprinting centers or uniparental disomy.^[24]
Methylation test. May detect deletions, uniparental disomies, and imprinting mutations, but not UBE3A gene mutation.^[24]
Paternal uniparental disomy (UPD) studies. Usually done after a normal FISH and methylation test.^[24]
Ubiquitin-protein ligase E3A (UBE3A) mutations. Is performed in patients with clinical presentation of Angelman syndrome, but negative methylation test.^[24]
Imprinting center (IC) mutations. Detects small deletions, but is only available in research centers.^[24]

Natural History, Complications & Prognosis

Newborns with Angelman syndrome usually weight less than averange when delivered.^[25]
Motor delay and jerky movements usually appear before 1 year of age.^[25]^[7]
Seizures could be present between 2 and 8 years of age.^[25]^[7]
Dysmorphic facies and scoliosis are aparent after 5 years of age.^[25]^[26]^[27]^[7]
Sexual developement begins and progresses at a normal time.^[28]^[29]
Dressing skills and use of certain utensils may happen.^[26]
Patients never develope proper language (5-10 learned word) and usually comunicate with signs.^[25]^[7]^[30]
At the end, patients do not acquire enough abilities to live by there own.^[25]
Prognosis will vary depending on the severity of symptoms and earliness of management.^[31]
Patients may have a normal life span.^[31]
The mortality rate of Angelman syndrome per 1000 patients/year was 15.84.^[32]

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]

Developement history. Normal birth, delayed motor milestones, with no loss of skills.^[35]^[7]
Clinical findings. Clinical features (puppet-like movements, speech impairment, feeding dificulties, unprovoked laughter, etc.) previously described, dysmorphic facies, and behavioural uniqueness.^[35]
Genetic testing. Deletion in chromosomal region 15q11-13 with absence of UBE3A gene.^[35]

Symptoms

Angelman syndrome is usually asymptomatic.

Physical Examination

Patients with Angelman syndrome usually appear dysmorphic.^[37]^[15]
The most common physical examination findings are:^[35]

Flat occiput ^[17]
Below average head size^[38]^[15]
Occipital groove^[17]
Protruding tongue^[17]^[15]
Tongue thrusting^[17]
Truncal hypotonia^[17]
Prognathia^[17]
Wide mouth^[17]
Wide spaced teeth^[17]
Strabismus^[17]
Light color of skin,hair, and eyes^[17]
Uplifted, flexed arm position during ambulation^[17]
Valgus positioned ankles^[17]
Obesity found in older child^[17]
Scoliosis^[17]^[15]

Laboratory Findings

Hematologic, metabolic, and chemical laboratory findings in Angelman syndrome are usually normal.^[35]

Imaging Findings

Usually, MRI and CT scans demonstrate normal structural finidings; in some cases, there may be cortical atrophy or demyelinating lesions.^[35]

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

Currently, there is no specific treatment for Angelman syndrome.^[41]
Treatment is only supportive and is amied to:^[41]^[42]
1. Mitigate gross and fine motor delays.^[41]^[42]^[7]^[15]
2. Improve communication with non-verbal methods (eg. use of communication devices, implement a sign language, exchange of image cards).^[41]^[42]^[7]^[15]
3. Intervention for autism spectrum disorder, when present.^[41]^[42]^[7]^[15]

Feeding in newborns may requiere special nipples due to poor sucking.^[15]^[43]
Antiepileptics are used for seizures, but there hasn't been a consensus on wich medication is the most appropiate.^[15]^[44]^[43]
Stimulants (methylphenidate) have been used to control hyperactivity behaviours.^[15]^[41]
Physiotherapy may improve range of movements and prevents joint stiffness.
Occupational therapy helps to ameliorate fine motor and oral-motor control.^[15]^[43]
Use of low-potency sedatives may help with disruptive nighttime wakefulness.^[15]^[45]^[41]
Orthopedic postures may be corrected with bracing.^[15]^[43]
Dietary recomendations should be made in patients with constipation and/or obesity.^[46]^[41]

Surgery

Sometimes fundoplication may be requiered for reflux symptoms.^[15]
Surgery may be needed to correct certain orthopedic problems (eg. severe scoliosis).^[15]^[43]
Surgery for tongue protrusion has not found to be effective.^[15]

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]

External links

References

↑ ^1.0 ^1.1 Template:WhoNamedIt
↑ 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.
↑ ^3.0 ^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.
↑ 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.
↑ 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.
↑ 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.
↑ ^7.00 ^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
↑ 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.
↑ Weeber E, Levenson J, Sweatt J (2002). "Molecular genetics of human cognition". Mol Interv. 2 (6): 376–91, 339. PMID 14993414.
↑ ^10.0 ^10.1 Williams, Charles. "Angelman Syndrome". National Organization of Rare Diseases. Retrieved 06/02/2020. Check date values in: |access-date= (help)
↑ 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.
↑ 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.
↑ ^13.0 ^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.
↑ ^14.0 ^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.
↑ ^15.00 ^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
↑ 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.
↑ ^17.00 ^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.
↑ ^18.0 ^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.
↑ "www.angelman.org" (PDF).
↑ "Angelman syndrome - Symptoms and causes - Mayo Clinic".
↑ 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.
↑
↑ 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.
↑ ^24.0 ^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.
↑ ^25.0 ^25.1 ^25.2 ^25.3 ^25.4 ^25.5 "www.ncbi.nlm.nih.gov" (PDF).
↑ ^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.
↑ 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.
↑ Lossie A, Driscoll D. "Transmission of Angelman syndrome by an affected mother". Genet Med. 1 (6): 262–6. PMID 11258627.
↑ 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.
↑ ^30.0 ^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.
↑ ^31.0 ^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.
↑ 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.
↑ 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.
↑ 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.
↑ ^35.0 ^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.
↑ 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.
↑ 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.
↑ "Angelman syndrome - Symptoms and causes - Mayo Clinic".
↑ 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.
↑ 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.
↑ ^41.0 ^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.
↑ ^42.0 ^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.
↑ ^43.0 ^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)
↑ 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.
↑ 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.
↑ 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

[doctor-1] 1.0 ^1.1 Template:WhoNamedIt

[Angelman2008-2] 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.

[pmid22830052-3] 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.

[pmid9585605-4] 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.

[Clayton-SmithPembrey1992-5] 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.

[pmid194551853-6] 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.

[pmid22670133-7] 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

[pmid27860204-8] 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.

[:1-10] 10.0 ^10.1 Williams, Charles. "Angelman Syndrome". National Organization of Rare Diseases. Retrieved 06/02/2020. Check date values in: |access-date= (help)

[pmid194551854-11] 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.

[pmid194551855-12] 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.

[:0-13] 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.

[pmid145106232-14] 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.

[pmid20445456-15] 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

[pmid194551852-16] 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.

[SidorovDeck20172-17] 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.

[Clayton-SmithPembrey19925-18] 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.

[urlwww.angelman.org2-19] "www.angelman.org" (PDF).

[urlAngelman_syndrome_-_Symptoms_and_causes_-_Mayo_Clinic-20] "Angelman syndrome - Symptoms and causes - Mayo Clinic".

[pmid26942024-21] 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.

[urlAngelmans_Syndrome_-_symptoms,_average,_Definition,_Description,_Demographics,_Causes_and_symptoms,_Diagnosis2-22] ↑

[pmid14510623-23] 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.

[pmid145106233-24] 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.

[urlwww.ncbi.nlm.nih.gov-25] 25.0 ^25.1 ^25.2 ^25.3 ^25.4 ^25.5 "www.ncbi.nlm.nih.gov" (PDF).

[pmid9072912-26] 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.

[pmid90729122-27] 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.

[pmid11258627-29] 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.

[pmid11432411-30] 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.

[pmid28494826-31] 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.

[HerbstByard2012-32] 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.

[pmid7625452-33] 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.

[pmid164707472-34] 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.

[pmid194551856-35] 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.

[pmid16470747-36] 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.

[pmid19455185-37] 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.

[urlAngelman_syndrome_-_Symptoms_and_causes_-_Mayo_Clinic2-38] "Angelman syndrome - Symptoms and causes - Mayo Clinic".

[LaanVein2005-39] 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.

[SidorovDeck2017-40] 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.

[pmid26040994-41] 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.

[pmid24876791-42] 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.

[pmid203013236-43] 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)

[pmid19453717-44] 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.

[pmid10392349-45] 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.

[pmid11748306-46] 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.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]

[14]

[15]

[16]

[17]

[18]

[19]

[20]

[21]

[22]

[23]

[24]

[25]

[26]

[27]

[28]

[29]

[30]

[31]

[32]

[33]

[34]

[35]

[36]

[37]

[38]

[39]

[40]

[41]

[42]

[43]

[44]

[45]

[46]