Aarskog-Scott syndrome: Difference between revisions

Latest revision as of 15:31, 17 September 2019

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vamsikrishna Gunnam M.B.B.S [2]

Synonyms and Keywords: Aarskog disease, Aarskog-Scott syndrome, AAS, Faciodigitogenital syndrome, Faciogenital dysplasia, FGDY, Scott Aarskog syndrome

Overview

Aarskog-Scott syndrome is a rare inherited disease distinguish by short stature, facial abnormalities, skeletal and genital anomalies. The Aarskog-Scott syndrome (AAS) is also known as the Aarskog syndrome, faciodigitogenital syndrome, shawl scrotum syndrome and facial genital dysplasia. In The United States of America in order to categorise a condition as a rare disease it should affect fewer than 200,000 people. Rare diseases also called as orphan diseases. Orphan Drug Act was passed on 1983 by congress for the rare diseases. Today an average of 25-30 million americans have been reported with rare diseases. The number of people with individual rare disease may be less but overall the number of people with rare diseases are large in number.

Historical Perspective

In 1970, Aarskog-Scott syndrome (AAS) was first described by Aarskog, a Norwegian pediatrician and human geneticist.
In 1971, Scott described the association between ligamentous laxity which results in hyperextensibility of the fingers, genu recurvatum, flat feet and Aarskog-Scott syndrome (AAS).^[1]
In 1973, Sugarman et al described an Mexican-American family in which 2 half brothers and their 2 maternal uncles had Aarskog syndrome.
In 1993, Teebi et al suggested that the disease Aarskog-Scott syndrome (AAS) follows autosomal dominant inheritance.^[2]
In 1978, Escobar and Weaver described a patient who is had symptoms of Noonan syndrome than Aarskog-Scott syndrome (AAS).^[3]
In 1981, Grier et al. suggested that Aarskog-Scott syndrome (AAS) follows autosomal dominant pattern of inheritance.^[4]
In 1984, Van den Bergh et al. mentioned a patient with Aarskog-Scott syndrome (AAS) development of syndrome of benign intracranial hypertension after minor head trauma.^[5]
In 1994, Fernandez et al. mentioned 10 Japanese patients who are positive with Aarskog syndrome.^[6]
In 1998, Logie and Porteous concluded that in patients with Aarskog-Scott syndrome (AAS) have normal intelligence.^[7]
In 2002, Lebel et al. is the one who found a missense mutation in the FGD1 gene.^[8]
In 2005, Orrico et al. described attention deficit-hyperactivity disorder (ADHD) in patient with Aarskog-Scott syndrome (AAS).^[9]
In 2010, Orrico et al. genetically confirmed 11 patients for Aarskog-Scott syndrome.^[10]

Detection of FGD1 mutations — Detection of *FGD1* mutations. (A) Schematic representation of the domains of the *FGD1* protein showing mutations (p.Glu380* and p.Gln664*) identified in patients with AAS. Arrows indicate the positions of the mutated nucleotides in *FGD1*. (B) sequencing results (p.Glu380* and p.Gln664*) detected in exon 5 and 12, respectively. The altered amino acids are shown in red. Case courtesy by Mariana Pérez-Coria et al^[11]

Classification

There is no established system for the classification of Aarskog-Scott syndrome (AAS).^[12]

Pathophysiology

Aarskog-Scott syndrome (AAS) is transmitted in X-linked recessive mode of inheritance.^[13]^[14]^[15]
In some cases Aarskog-Scott syndrome (AAS) is transmitted in autosomal dominant mode of inheritance.^[16]^[17]
It is understood that Aarskog-Scott syndrome (AAS) is the result caused by a mutation in FGD1 gene.
FGD1 gene mapped to the Xp11.21 region is located on X chromosome.
Normally, in most of the situations males have one X chromosome and females have two X chromosomes.
When mutation occurs in FGD1 gene of males may result in the Aarskog-Scott syndrome (AAS).^[18]
But, in females the mutation had to occur in both X chromosomes to manifest the disease Aarskog-Scott syndrome (AAS).
In females if the mutation occurs in only one X chromosome then it results in mild features of Aarskog-Scott syndrome (AAS).
The gene FGD1 specifically encodes for guanine nucleotide exchange factor (GEF).^[19]
Guanine nucleotide exchange factor (GEF) inturn activates Cdc42 which belongs to Ras homology of the p21 GTPases.^[20]^[21]^[22]
Upon activation of Cdc42, FGD1 proteins they activate the following:^[23]^[24]^[25]^[26]^[27]^[28]^[29]^[30]^[31]^[32]
- Fibroblasts
- Cytoskeletal elements which are involved in
  - Cellular signaling
  - Adhesion
  - Migration
- c- N-terminal kinase (JNK) signaling cascade which involves:
  - Cell growth
  - Apoptosis
  - Cellular differentiation
These abnormalities of FGD1/Cdc42 signaling pathway may produce an defective embryonic development and abnormal endochondral and intramembranous bone formation and leads to Aarskog-Scott syndrome (AAS).

Causes

Genetic Cause

Aarskog-Scott syndrome (AAS) is caused by a mutation in the FGD1 gene.

Differentiating Aarskog-Scott syndrome from other Diseases

Aarskog-Scott syndrome (AAS) must be differentiated from Robinow syndrome, Noonan syndrome, pseudohypoparathyroidism, Silver-Russell and SHORT syndrome.^[33]^[34]^[35]

Epidemiology and Demographics

Incidence

The incidence of Aarskog-Scott syndrome (AAS) is unknown.^[36]
Till now there are 29 cases of Aarskog-Scott syndrome (AAS) had been diagnosed worldwide.

Prevalence

The prevalence of Aarskog-Scott syndrome (AAS) is 1/25 000 worldwide.^[37]
The prevalence of Aarskog-Scott syndrome (AAS) is 1-9 per 1,000,000 in Europe.

Age

Aarskog-Scott syndrome (AAS) commonly affects individuals of younger age especially in childwood.

Race

There is no racial predilection to Aarskog-Scott syndrome (AAS).

Gender

Aarskog-Scott syndrome (AAS) affects men more commonly than in women.^[38]

Risk Factors

There are no established risk factors for Aarskog-Scott syndrome (AAS).

Screening

There is insufficient evidence to recommend routine screening for Aarskog-Scott syndrome (AAS).

Natural History, Complications and Prognosis

Natural History

The symptoms of Aarskog-Scott syndrome (AAS) usually develop in the first decade of life, and start with symptoms such as delayed growth spurt.
The symptoms of Aarskog-Scott syndrome (AAS) typically develop in 2 to 4 years of age.

Complications

Common complications of Aarskog-Scott syndrome (AAS) include:^[39]^[40]^[41]
- Cryptorchidism
- Spina bifida occulta
- Cervical spine abnormalities
- Scoliosis
- Camptodactyly
- Lymphoedema
- Optic nerve hypoplasia
- Retinal vessel tortuosity

Prognosis

Prognosis is generally good with Aarskog-Scott syndrome (AAS) patients.

Diagnostic study of choice

Aarskog-Scott syndrome (AAS) is primarily diagnosed based on clinical presentation based on Teebi criteria which includes:^[42]^[43]^[44]^[45]
- Short stature
- Hypertelorism
- Fold of the lower lip
- Brachydactyly
- Interdigital webbing
- Shawl scrotum
- Long philtrum
- Mild facial hypoplasia

Patients with clinical features of Aarskog syndrome-(A) Patient 1; note distinctive facial characteristics and interdigital tracts in both hands. (B) Patient 2; discrete facial features and the shawl scrotum can be appreciated. (C) Patient 3 and his mother (patient 8); note prominent forehead, widow's peak, hypertelorism, and fold under the lower lip. (D) Patient 4 with widow's peak, midface hypoplasia, ptosis, clinodactyly, and brachydactyly. (E) Patient 5, brother of patient 4, with distinctive facial features, clinodactyly, and brachydactyly. Case courtesy by Mariana Pérez-Coria et al^[46]

History and Symptoms

Common Symptoms

Common symptoms of Aarskog-Scott syndrome (AAS) include:^[25]^[47]

Short stature (evident by 1-3 years of age)
Mental retardation
Hypertelorism
Umbilical hernia
Shawl scrotum
Hypospadias
Undescended testes

Physical Examination

HEENT

Facial features are very prominent and important for the diagnosis of Aarskog-Scott syndrome (AAS) which include:^[48]^[49]^[50]^[51]^[52]

Round face
Facial edema with downward slanting palpebral fissures
Short nose along with anteverted nares
Long philtrum
Ocular hypertelorism with ptosis
Maxillary hypoplasia
A broad upper lip with a crease below the lower lip
Abnormal auriculares

Neck

Short neck
Webbing of sides of the neck

Extremities

Small, broad hands and feet
Short fingers and toes (brachydactyly)
Clinodactyly
Mild webbing between the fingers and toes
Simian crease
Broad thumbs and big toes

Laboratory Findings

There are no diagnostic laboratory findings associated with Aarskog-Scott syndrome (AAS).

Electrocardiogram

There are no ECG findings associated with Aarskog-Scott syndrome (AAS).

X-Ray Findings

Scoliosis- a) Early postoperative X-ray (b) 10 years follow-up X-ray.Case courtesy Kerim Sariyilmaz^[54]
There are no x-ray findings associated with Aarskog-Scott syndrome (AAS). However, an x-ray may be helpful in the diagnosis of complications of Aarskog-Scott syndrome (AAS), which include:^[55]^[56]^[57]
- Skeletal abnormalities
- Tooth abnormalities
- Scoliosis

Echocardiography and Ultrasound

The ultrasound can help in detecting the undescended testis associated with Aarskog-Scott syndrome (AAS).^[58]

CT-Scan Findings

Head CT scan may be helpful in the diagnosis of Aarskog-Scott syndrome (AAS). Findings on CT scan suggestive Aarskog-Scott syndrome (AAS) include:
- Cystic development

MRI Findings

There are no MRI findings associated with Aarskog-Scott syndrome (AAS).

Medical Therapy

There is no treatment for Aarskog-Scott syndrome (AAS); the mainstay of therapy is symptomatic care.
Patients with short stature are treated with growth hormone, which shows promising results in increasing the height of the patients.^[59]^[60]

Interventions

There are some recommended therapeutic interventions for the management of Aarskog-Scott syndrome (AAS), which includes speech pathologists, audiologists and eye specialists who can improve the quality of the patient's life.

Surgery

Surgery is usually reserved for patients with congenital or structural malformations which involves the following:
- Hypospadias(opening of the penis is on the underside rather than the tip)
- Inguinal or umbilical hernias
- Cryptorchidism(undescended testis)

Primary Prevention

There are no established measures for the primary prevention of Aarskog-Scott syndrome (AAS).

Secondary Prevention

There are no established measures for the secondary prevention of Aarskog-Scott syndrome (AAS).

References

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↑ Grier RE, Farrington FH, Kendig R, Mamunes P (1983). "Autosomal dominant inheritance of the Aarskog syndrome". Am J Med Genet. 15 (1): 39–46. doi:10.1002/ajmg.1320150105. PMID 6344635.
↑ Escobar V, Weaver DD (1978). "Aarskog syndrome. New findings and genetic analysis". JAMA. 240 (24): 2638–41. doi:10.1001/jama.240.24.2638. PMID 712980.
↑ Grier, Robert E.; Farrington, Frank H.; Kendig, Robert; Mamunes, Peter; Opitz, John M. (1983). "Autosomal dominant inheritance of the Aarskog syndrome". American Journal of Medical Genetics. 15 (1): 39–46. doi:10.1002/ajmg.1320150105. ISSN 0148-7299.
↑ van den Bergh P, Fryns JP, Wilms G, Piot R, Dralands G, van den Bergh R (1984). "Anomalous cerebral venous drainage in Aarskog syndrome". Clin Genet. 25 (3): 288–94. doi:10.1111/j.1399-0004.1984.tb01991.x. PMID 6705262.
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↑ Orrico A, Galli L, Buoni S, Hayek G, Luchetti A, Lorenzini S; et al. (2005). "Attention-deficit/hyperactivity disorder (ADHD) and variable clinical expression of Aarskog-Scott syndrome due to a novel FGD1 gene mutation (R408Q)". Am J Med Genet A. 135 (1): 99–102. doi:10.1002/ajmg.a.30700. PMID 15809997.
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↑ Grier RE, Farrington FH, Kendig R, Mamunes P (1983). "Autosomal dominant inheritance of the Aarskog syndrome". Am J Med Genet. 15 (1): 39–46. doi:10.1002/ajmg.1320150105. PMID 6344635.
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↑ Zou, Weiguo; Greenblatt, Matthew B.; Shim, Jae-Hyuck; Kant, Shashi; Zhai, Bo; Lotinun, Sutada; Brady, Nicholas; Hu, Dorothy Zhang; Gygi, Steven P.; Baron, Roland; Davis, Roger J.; Jones, Dallas; Glimcher, Laurie H. (2011). "MLK3 regulates bone development downstream of the faciogenital dysplasia protein FGD1 in mice". Journal of Clinical Investigation. 121 (11): 4383–4392. doi:10.1172/JCI59041. ISSN 0021-9738.
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↑ ^25.0 ^25.1 Schwartz CE, Gillessen-Kaesbach G, May M, Cappa M, Gorski J, Steindl K; et al. (2000). "Two novel mutations confirm FGD1 is responsible for the Aarskog syndrome". Eur J Hum Genet. 8 (11): 869–74. doi:10.1038/sj.ejhg.5200553. PMID 11093277.
↑ Pasteris NG, Buckler J, Cadle AB, Gorski JL (1997). "Genomic organization of the faciogenital dysplasia (FGD1; Aarskog syndrome) gene". Genomics. 43 (3): 390–4. doi:10.1006/geno.1997.4837. PMID 9268645.
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↑ Orrico, A.; Galli, L.; Faivre, L.; Clayton-Smith, J.; Azzarello-Burri, S.M.; Hertz, J.M.; Jacquemont, S.; Taurisano, R.; Arroyo Carrera, I.; Tarantino, E.; Devriendt, K.; Melis, D.; Thelle, T.; Meinhardt, U.; Sorrentino, V. (2010). "Aarskog-Scott syndrome: Clinical update and report of nine novel mutations of theFGD1gene". American Journal of Medical Genetics Part A. 152A (2): 313–318. doi:10.1002/ajmg.a.33199. ISSN 1552-4825.
↑ Egorov M, Polishchuk R (2019). "Identification of CDC42 Effectors Operating in FGD1-Dependent Trafficking at the Golgi". Front Cell Dev Biol. 7: 7. doi:10.3389/fcell.2019.00007. PMC 6369352. PMID 30778386.
↑ Parıltay E, Hazan F, Ataman E, Demir K, Etlik Ö, Özbek E; et al. (2016). "A novel splice site mutation of FGD1 gene in an Aarskog-Scott syndrome patient with a large anterior fontanel". J Pediatr Endocrinol Metab. 29 (9): 1111–4. doi:10.1515/jpem-2015-0482. PMID 27544718.
↑ Weinstein, Lee S. (2016). "GNAS and McCune-Albright/Fibrous Dysplasia, Albright Hereditary Osteodystrophy, and Pseudohypoparathyroidism": 1178–1181. doi:10.1093/med/9780199934522.003.0179.
↑ Reza Jabalameli, M.; Briceno, Ignacio; Martinez, Julio; Briceno, Ignacio; J. Pengelly, Reuben; Ennis, Sarah; Collins, Andrew (2016). "Aarskog-Scott syndrome: phenotypic and genetic heterogeneity". AIMS Genetics. 3 (1): 49–59. doi:10.3934/genet.2016.1.49. ISSN 2377-1143.
↑ Reza Jabalameli, M.; Briceno, Ignacio; Martinez, Julio; Briceno, Ignacio; J. Pengelly, Reuben; Ennis, Sarah; Collins, Andrew (2016). "Aarskog-Scott syndrome: phenotypic and genetic heterogeneity". AIMS Genetics. 3 (1): 49–59. doi:10.3934/genet.2016.1.49. ISSN 2377-1143.
↑ Orrico A, Galli L, Clayton-Smith J, Fryns JP (2015) Clinical utility gene card for: Aarskog-Scott Syndrome (faciogenital dysplasia) - update 2015. Eur J Hum Genet 23 (4):. DOI:10.1038/ejhg.2014.178 PMID: 25227149
↑ Reza Jabalameli, M.; Briceno, Ignacio; Martinez, Julio; Briceno, Ignacio; J. Pengelly, Reuben; Ennis, Sarah; Collins, Andrew (2016). "Aarskog-Scott syndrome: phenotypic and genetic heterogeneity". AIMS Genetics. 3 (1): 49–59. doi:10.3934/genet.2016.1.49. ISSN 2377-1143.
↑ Jogiya, Aryan; Sandy, Charles (2009). "Mild Optic Nerve Hypoplasia with Retinal Venous Tortuosity in Aarskog (Facial-Digital-Genital) Syndrome". Ophthalmic Genetics. 26 (3): 139–141. doi:10.1080/13816810500229025. ISSN 1381-6810.
↑ Pizio HF, Scott MH, Richard JM (1994). "Tortuosity of the retinal vessels in Aarskog syndrome (faciogenital dysplasia)". Ophthalmic Genet. 15 (1): 37–40. PMID 7953251.
↑ Grier RE, Farrington FH, Kendig R, Mamunes P (1983). "Autosomal dominant inheritance of the Aarskog syndrome". Am J Med Genet. 15 (1): 39–46. doi:10.1002/ajmg.1320150105. PMID 6344635.
↑ Ahmed A, Mufeed A, Ramachamparambathu AK, Hasoon U (2016). "Identifying Aarskog Syndrome". J Clin Diagn Res. 10 (12): ZD09–ZD11. doi:10.7860/JCDR/2016/22180.8982. PMC 5296586. PMID 28209013.
↑ Grier RE, Farrington FH, Kendig R, Mamunes P (1983). "Autosomal dominant inheritance of the Aarskog syndrome". Am J Med Genet. 15 (1): 39–46. doi:10.1002/ajmg.1320150105. PMID 6344635.
↑ Darendeliler F, Larsson P, Neyzi O, Price AD, Hagenäs L, Sipilä I; et al. (2003). "Growth hormone treatment in Aarskog syndrome: analysis of the KIGS (Pharmacia International Growth Database) data". J Pediatr Endocrinol Metab. 16 (8): 1137–42. PMID 14594174.
↑ Orrico A, Galli L, Cavaliere ML, Garavelli L, Fryns JP, Crushell E; et al. (2004). "Phenotypic and molecular characterisation of the Aarskog-Scott syndrome: a survey of the clinical variability in light of FGD1 mutation analysis in 46 patients". Eur J Hum Genet. 12 (1): 16–23. doi:10.1038/sj.ejhg.5201081. PMID 14560308.
↑ "Identification of novel mutations in Mexican patients with Aarskog–Scott syndrome".
↑ Şıklar Z, Berberoğlu M (2014). "Syndromic disorders with short stature". J Clin Res Pediatr Endocrinol. 6 (1): 1–8. doi:10.4274/Jcrpe.1149. PMC 3986733. PMID 24637303.
↑ Reza Jabalameli, M.; Briceno, Ignacio; Martinez, Julio; Briceno, Ignacio; J. Pengelly, Reuben; Ennis, Sarah; Collins, Andrew (2016). "Aarskog-Scott syndrome: phenotypic and genetic heterogeneity". AIMS Genetics. 3 (1): 49–59. doi:10.3934/genet.2016.1.49. ISSN 2377-1143.
↑ Bedoyan JK, Friez MJ, DuPont B, Ahmad A (2009). "First case of deletion of the faciogenital dysplasia 1 (FGD1) gene in a patient with Aarskog-Scott syndrome". Eur J Med Genet. 52 (4): 262–4. doi:10.1016/j.ejmg.2008.12.001. PMID 19110080.
↑ Teebi AS, Rucquoi JK, Meyn MS (1993). "Aarskog syndrome: report of a family with review and discussion of nosology". Am J Med Genet. 46 (5): 501–9. doi:10.1002/ajmg.1320460508. PMID 8322809.
↑ Ulaş, Cıkla; Giampietro, Philip F.; Sadighi, Alireza; Başkaya, Mustafa K. (2014). "Ruptured Posterior Communicating Artery Aneurysm Associated with Aarskog Syndrome". NMC Case Report Journal. 2 (3): 85–87. doi:10.2176/nmccrj.2014-0022. ISSN 2188-4226.
↑ Ahmed A, Mufeed A, Ramachamparambathu AK, Hasoon U (2016). "Identifying Aarskog Syndrome". J Clin Diagn Res. 10 (12): ZD09–ZD11. doi:10.7860/JCDR/2016/22180.8982. PMC 5296586. PMID 28209013.
↑ Ahmed A, Mufeed A, Ramachamparambathu AK, Hasoon U (2016). "Identifying Aarskog Syndrome". J Clin Diagn Res. 10 (12): ZD09–ZD11. doi:10.7860/JCDR/2016/22180.8982. PMC 5296586. PMID 28209013.
↑ "Aarskog-Scott syndrome: An unusual cause of scoliosis".
↑ Sariyilmaz K, Ozkunt O, Korkmaz M, Dikici F, Domanic U (2017). "Aarskog-Scott syndrome: An unusual cause of scoliosis". J Craniovertebr Junction Spine. 8 (3): 283–284. doi:10.4103/jcvjs.JCVJS_133_16. PMC 5634118. PMID 29021683.
↑ Gorski JL, Estrada L, Hu C, Liu Z (2000). "Skeletal-specific expression of Fgd1 during bone formation and skeletal defects in faciogenital dysplasia (FGDY; Aarskog syndrome)". Dev Dyn. 218 (4): 573–86. doi:10.1002/1097-0177(2000)9999:9999<::AID-DVDY1015>3.0.CO;2-F. PMID 10906777.
↑ Ahmed A, Mufeed A, Ramachamparambathu AK, Hasoon U (2016). "Identifying Aarskog Syndrome". J Clin Diagn Res. 10 (12): ZD09–ZD11. doi:10.7860/JCDR/2016/22180.8982. PMC 5296586. PMID 28209013.
↑ Tasian GE, Copp HL, Baskin LS (2011). "Diagnostic imaging in cryptorchidism: utility, indications, and effectiveness". J Pediatr Surg. 46 (12): 2406–13. doi:10.1016/j.jpedsurg.2011.08.008. PMC 3712862. PMID 22152893.
↑ Deodati A, Cianfarani S (2017). "The Rationale for Growth Hormone Therapy in Children with Short Stature". J Clin Res Pediatr Endocrinol. 9 (Suppl 2): 23–32. doi:10.4274/jcrpe.2017.S003. PMC 5790327. PMID 29280742.
↑ Frindik JP, Kemp SF (2010). "Managing idiopathic short stature: role of somatropin (rDNA origin) for injection". Biologics. 4: 147–55. PMC 2898102. PMID 20631818.

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[pmid5173168-1] Scott CI (1971). "Unusual facies, joint hypermobility, genital anomaly and short stature: a new dysmorphic syndrome". Birth Defects Orig Artic Ser. 7 (6): 240–6. PMID 5173168.

[pmid6344635-2] Grier RE, Farrington FH, Kendig R, Mamunes P (1983). "Autosomal dominant inheritance of the Aarskog syndrome". Am J Med Genet. 15 (1): 39–46. doi:10.1002/ajmg.1320150105. PMID 6344635.

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@@ Line 1: / Line 1: @@
-'''''Synonyms and Keywords:''''' Aarskog disease, Aarskog-Scott syndrome, AAS, Faciodigitogenital syndrome, Faciogenital dysplasia, FGDY, Scott Aarskog syndrome{{Infobox_Disease |
+__NOTOC__
-  Name           = {{PAGENAME}} |
-  Image          = |
-  Caption        = |
-  DiseasesDB     = 29329 |
-  ICD10          = {{ICD10|Q|87|1|q|80}} |
-  ICD9           = {{ICD9|759.89}} |
-  ICDO           = |
-  OMIM           = 100050 |
-  MedlinePlus    = |
-  eMedicineSubj  = |
-  eMedicineTopic = |
-  MeshID         = |
-}}
+{{CMG}}; {{AE}} {{VKG}}
+'''''Synonyms and Keywords:''''' Aarskog disease, Aarskog-Scott syndrome, AAS, Faciodigitogenital syndrome, Faciogenital dysplasia, FGDY, Scott Aarskog syndrome
 == Overview ==
 '''Aarskog-Scott syndrome''' is a rare [[inherited disease]] distinguish by [[short stature]], [[facial]] abnormalities, [[Skeleton|skeletal]] and [[genital]] anomalies. The Aarskog-Scott syndrome (AAS) is also known as the Aarskog syndrome, faciodigitogenital syndrome, shawl [[scrotum]] syndrome and facial [[genital]] [[dysplasia]]. In The United States of America in order to categorise a [[condition]] as a [[rare disease]] it should affect fewer than 200,000 people. [[Rare diseases]] also called as [[Orphan disease|orphan diseases]]. [[Orphan Drug Act]] was passed on 1983 by congress for the [[rare diseases]]. Today an average of 25-30 million americans have been reported with [[rare diseases]]. The number of people with individual [[rare disease]] may be less but overall the number of people with [[rare diseases]] are large in number.
 == Historical Perspective ==
 * In 1970, Aarskog-Scott syndrome (AAS) was first described by Aarskog, a Norwegian [[pediatrician]] and human [[geneticist]].
 *In 1971, Scott described the association between [[Ligamentous laxity|ligamentous]] laxity which results in hyperextensibility of the fingers, [[genu recurvatum]], flat feet and Aarskog-Scott syndrome (AAS).<ref name="pmid5173168">{{cite journal| author=Scott CI| title=Unusual facies, joint hypermobility, genital anomaly and short stature: a new dysmorphic syndrome. | journal=Birth Defects Orig Artic Ser | year= 1971 | volume= 7 | issue= 6 | pages= 240-6 | pmid=5173168 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5173168  }}</ref>
 *In 1973, Sugarman et al described an Mexican-American family in which 2 half brothers and their 2 maternal uncles had Aarskog syndrome.
 *In 1993, Teebi et al suggested that the disease Aarskog-Scott syndrome (AAS) follows [[autosomal dominant]] [[inheritance]].<ref name="pmid6344635">{{cite journal| author=Grier RE, Farrington FH, Kendig R, Mamunes P| title=Autosomal dominant inheritance of the Aarskog syndrome. | journal=Am J Med Genet | year= 1983 | volume= 15 | issue= 1 | pages= 39-46 | pmid=6344635 | doi=10.1002/ajmg.1320150105 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6344635  }}</ref>
-*In 1978, Escobar and Weaver described a patient who is had symptoms of Noonan syndrome than Aarskog-Scott syndrome (AAS).<ref name="pmid712980">{{cite journal| author=Escobar V, Weaver DD| title=Aarskog syndrome. New findings and genetic analysis. | journal=JAMA | year= 1978 | volume= 240 | issue= 24 | pages= 2638-41 | pmid=712980 | doi=10.1001/jama.240.24.2638 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=712980  }}</ref>
+*In 1978, Escobar and Weaver described a patient who is had symptoms of [[Noonan syndrome]] than Aarskog-Scott syndrome (AAS).<ref name="pmid712980">{{cite journal| author=Escobar V, Weaver DD| title=Aarskog syndrome. New findings and genetic analysis. | journal=JAMA | year= 1978 | volume= 240 | issue= 24 | pages= 2638-41 | pmid=712980 | doi=10.1001/jama.240.24.2638 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=712980  }}</ref>
-*In 1981, Grier et al. suggested that Aarskog-Scott syndrome (AAS) follows autosomal dominant pattern of inheritance.<ref name="GrierFarrington1983">{{cite journal|last1=Grier|first1=Robert E.|last2=Farrington|first2=Frank H.|last3=Kendig|first3=Robert|last4=Mamunes|first4=Peter|last5=Opitz|first5=John M.|title=Autosomal dominant inheritance of the Aarskog syndrome|journal=American Journal of Medical Genetics|volume=15|issue=1|year=1983|pages=39–46|issn=0148-7299|doi=10.1002/ajmg.1320150105}}</ref>
+*In 1981, Grier et al. suggested that Aarskog-Scott syndrome (AAS) follows [[autosomal dominant]] pattern of [[inheritance]].<ref name="GrierFarrington1983">{{cite journal|last1=Grier|first1=Robert E.|last2=Farrington|first2=Frank H.|last3=Kendig|first3=Robert|last4=Mamunes|first4=Peter|last5=Opitz|first5=John M.|title=Autosomal dominant inheritance of the Aarskog syndrome|journal=American Journal of Medical Genetics|volume=15|issue=1|year=1983|pages=39–46|issn=0148-7299|doi=10.1002/ajmg.1320150105}}</ref>
-*In 1984, Van den Bergh et al. mentioned a patient with Aarskog-Scott syndrome (AAS) development of syndrome of benign intracranial hypertension after minor head trauma.<ref name="pmid6705262">{{cite journal| author=van den Bergh P, Fryns JP, Wilms G, Piot R, Dralands G, van den Bergh R| title=Anomalous cerebral venous drainage in Aarskog syndrome. | journal=Clin Genet | year= 1984 | volume= 25 | issue= 3 | pages= 288-94 | pmid=6705262 | doi=10.1111/j.1399-0004.1984.tb01991.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6705262  }}</ref>
+*In 1984, Van den Bergh et al. mentioned a patient with Aarskog-Scott syndrome (AAS) development of syndrome of benign [[intracranial hypertension]] after minor [[head]] [[trauma]].<ref name="pmid6705262">{{cite journal| author=van den Bergh P, Fryns JP, Wilms G, Piot R, Dralands G, van den Bergh R| title=Anomalous cerebral venous drainage in Aarskog syndrome. | journal=Clin Genet | year= 1984 | volume= 25 | issue= 3 | pages= 288-94 | pmid=6705262 | doi=10.1111/j.1399-0004.1984.tb01991.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6705262  }}</ref>
 *In 1994, Fernandez et al. mentioned 10 Japanese patients who are positive with Aarskog syndrome.<ref name="pmid8209909">{{cite journal| author=Fernandez I, Tsukahara M, Mito H, Yoshii H, Uchida M, Matsuo K et al.| title=Congenital heart defects in Aarskog syndrome. | journal=Am J Med Genet | year= 1994 | volume= 50 | issue= 4 | pages= 318-22 | pmid=8209909 | doi=10.1002/ajmg.1320500404 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8209909  }}</ref>
-*In 1998, Logie and Porteous concluded that in patients with Aarskog-Scott syndrome (AAS) have normal intelligence.<ref name="pmid9875050">{{cite journal| author=Logie LJ, Porteous ME| title=Intelligence and development in Aarskog syndrome. | journal=Arch Dis Child | year= 1998 | volume= 79 | issue= 4 | pages= 359-60 | pmid=9875050 | doi=10.1136/adc.79.4.359 | pmc=1717704 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9875050  }}</ref>
+*In 1998, Logie and Porteous concluded that in patients with Aarskog-Scott syndrome (AAS) have normal [[Intelligence test|intelligence]].<ref name="pmid9875050">{{cite journal| author=Logie LJ, Porteous ME| title=Intelligence and development in Aarskog syndrome. | journal=Arch Dis Child | year= 1998 | volume= 79 | issue= 4 | pages= 359-60 | pmid=9875050 | doi=10.1136/adc.79.4.359 | pmc=1717704 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9875050  }}</ref>
-*In 2002, Lebel et al. is the one who found a missense mutation in the FGD1 gene.<ref name="pmid11940089">{{cite journal| author=Lebel RR, May M, Pouls S, Lubs HA, Stevenson RE, Schwartz CE| title=Non-syndromic X-linked mental retardation associated with a missense mutation (P312L) in the FGD1 gene. | journal=Clin Genet | year= 2002 | volume= 61 | issue= 2 | pages= 139-45 | pmid=11940089 | doi=10.1034/j.1399-0004.2002.610209.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11940089  }}</ref>
+*In 2002, Lebel et al. is the one who found a [[Missense mutation|missense]] mutation in the [[FGD1]] gene.<ref name="pmid11940089">{{cite journal| author=Lebel RR, May M, Pouls S, Lubs HA, Stevenson RE, Schwartz CE| title=Non-syndromic X-linked mental retardation associated with a missense mutation (P312L) in the FGD1 gene. | journal=Clin Genet | year= 2002 | volume= 61 | issue= 2 | pages= 139-45 | pmid=11940089 | doi=10.1034/j.1399-0004.2002.610209.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11940089  }}</ref>
-*In 2005, Orrico et al. described attention deficit-hyperactivity disorder (ADHD) in patient with Aarskog-Scott syndrome (AAS).<ref name="pmid15809997">{{cite journal| author=Orrico A, Galli L, Buoni S, Hayek G, Luchetti A, Lorenzini S et al.| title=Attention-deficit/hyperactivity disorder (ADHD) and variable clinical expression of Aarskog-Scott syndrome due to a novel FGD1 gene mutation (R408Q). | journal=Am J Med Genet A | year= 2005 | volume= 135 | issue= 1 | pages= 99-102 | pmid=15809997 | doi=10.1002/ajmg.a.30700 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15809997  }}</ref>
+*In 2005, Orrico et al. described attention deficit-hyperactivity disorder ([[Attention-deficit hyperactivity disorder|ADHD]]) in [[patient]] with Aarskog-Scott syndrome (AAS).<ref name="pmid15809997">{{cite journal| author=Orrico A, Galli L, Buoni S, Hayek G, Luchetti A, Lorenzini S et al.| title=Attention-deficit/hyperactivity disorder (ADHD) and variable clinical expression of Aarskog-Scott syndrome due to a novel FGD1 gene mutation (R408Q). | journal=Am J Med Genet A | year= 2005 | volume= 135 | issue= 1 | pages= 99-102 | pmid=15809997 | doi=10.1002/ajmg.a.30700 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15809997  }}</ref>
-*In 2010, Orrico et al. genetically confirmed 11 patients for Aarskog-Scott syndrome.<ref name="pmid20082460">{{cite journal| author=Orrico A, Galli L, Faivre L, Clayton-Smith J, Azzarello-Burri SM, Hertz JM et al.| title=Aarskog-Scott syndrome: clinical update and report of nine novel mutations of the FGD1 gene. | journal=Am J Med Genet A | year= 2010 | volume= 152A | issue= 2 | pages= 313-8 | pmid=20082460 | doi=10.1002/ajmg.a.33199 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20082460  }}</ref>
+*In 2010, Orrico et al. [[genetically]] confirmed 11 patients for Aarskog-Scott syndrome.<ref name="pmid20082460">{{cite journal| author=Orrico A, Galli L, Faivre L, Clayton-Smith J, Azzarello-Burri SM, Hertz JM et al.| title=Aarskog-Scott syndrome: clinical update and report of nine novel mutations of the FGD1 gene. | journal=Am J Med Genet A | year= 2010 | volume= 152A | issue= 2 | pages= 313-8 | pmid=20082460 | doi=10.1002/ajmg.a.33199 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20082460  }}</ref>
+[[File:FGD1 mutations in Aarskog-Scott syndrome.jpg|alt=Detection of FGD1 mutations|thumb|Detection of ''FGD1'' mutations. (A) Schematic representation of the domains of the ''FGD1'' protein showing mutations (p.Glu380* and p.Gln664*) identified in patients with AAS. Arrows indicate the positions of the mutated nucleotides in ''FGD1''. (B) sequencing results (p.Glu380* and p.Gln664*) detected in exon 5 and 12, respectively. The altered amino acids are shown in red. Case courtesy by Mariana Pérez-Coria et al<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4444161/|title=Identification of novel mutations in Mexican patients with Aarskog–Scott syndrome|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref>]]
+<br />
 == Classification ==
+* There is no established system for the [[classification]] of Aarskog-Scott syndrome (AAS).<ref name="pmid11181572">{{cite journal| author=Estrada L, Caron E, Gorski JL| title=Fgd1, the Cdc42 guanine nucleotide exchange factor responsible for faciogenital dysplasia, is localized to the subcortical actin cytoskeleton and Golgi membrane. | journal=Hum Mol Genet | year= 2001 | volume= 10 | issue= 5 | pages= 485-95 | pmid=11181572 | doi=10.1093/hmg/10.5.485 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11181572  }}</ref>
-* There is no established system for the classification of Aarskog-Scott syndrome (AAS).<ref name="pmid11181572">{{cite journal| author=Estrada L, Caron E, Gorski JL| title=Fgd1, the Cdc42 guanine nucleotide exchange factor responsible for faciogenital dysplasia, is localized to the subcortical actin cytoskeleton and Golgi membrane. | journal=Hum Mol Genet | year= 2001 | volume= 10 | issue= 5 | pages= 485-95 | pmid=11181572 | doi=10.1093/hmg/10.5.485 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11181572  }}</ref>
 == Pathophysiology ==
+* Aarskog-Scott syndrome (AAS) is transmitted in [[X-linked recessive]] mode of [[inheritance]].<ref name="pmid7954831">{{cite journal| author=Pasteris NG, Cadle A, Logie LJ, Porteous ME, Schwartz CE, Stevenson RE et al.| title=Isolation and characterization of the faciogenital dysplasia (Aarskog-Scott syndrome) gene: a putative Rho/Rac guanine nucleotide exchange factor. | journal=Cell | year= 1994 | volume= 79 | issue= 4 | pages= 669-78 | pmid=7954831 | doi=10.1016/0092-8674(94)90552-5 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7954831  }}</ref><ref name="pmid9268645">{{cite journal| author=Pasteris NG, Buckler J, Cadle AB, Gorski JL| title=Genomic organization of the faciogenital dysplasia (FGD1; Aarskog syndrome) gene. | journal=Genomics | year= 1997 | volume= 43 | issue= 3 | pages= 390-4 | pmid=9268645 | doi=10.1006/geno.1997.4837 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9268645  }}</ref><ref name="pmid4155960">{{cite journal| author=Aarskog D| title=A familial syndrome of short stature associated with facial dysplasia and genital anomalies. | journal=Birth Defects Orig Artic Ser | year= 1971 | volume= 7 | issue= 6 | pages= 235-9 | pmid=4155960 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4155960  }}</ref>
-* Aarskog-Scott syndrome (AAS) is transmitted in X-linked recessive mode of inheritance.<ref name="pmid7954831">{{cite journal| author=Pasteris NG, Cadle A, Logie LJ, Porteous ME, Schwartz CE, Stevenson RE et al.| title=Isolation and characterization of the faciogenital dysplasia (Aarskog-Scott syndrome) gene: a putative Rho/Rac guanine nucleotide exchange factor. | journal=Cell | year= 1994 | volume= 79 | issue= 4 | pages= 669-78 | pmid=7954831 | doi=10.1016/0092-8674(94)90552-5 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7954831  }}</ref><ref name="pmid4155960">{{cite journal| author=Aarskog D| title=A familial syndrome of short stature associated with facial dysplasia and genital anomalies. | journal=Birth Defects Orig Artic Ser | year= 1971 | volume= 7 | issue= 6 | pages= 235-9 | pmid=4155960 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4155960  }}</ref>
+*In some cases Aarskog-Scott syndrome (AAS) is transmitted in [[autosomal dominant]] mode of [[inheritance]].<ref name="pmid63446352">{{cite journal| author=Grier RE, Farrington FH, Kendig R, Mamunes P| title=Autosomal dominant inheritance of the Aarskog syndrome. | journal=Am J Med Genet | year= 1983 | volume= 15 | issue= 1 | pages= 39-46 | pmid=6344635 | doi=10.1002/ajmg.1320150105 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6344635  }}</ref><ref name="BawleTyrkus1984">{{cite journal|last1=Bawle|first1=E.|last2=Tyrkus|first2=M.|last3=Lipman|first3=S.|last4=Bozimowski|first4=D.|last5=Opitz|first5=John M.|title=Aarskog syndrome: Full male and female expression associated with an X-autosome translocation|journal=American Journal of Medical Genetics|volume=17|issue=3|year=1984|pages=595–602|issn=0148-7299|doi=10.1002/ajmg.1320170307}}</ref>
-*In some cases Aarskog-Scott syndrome (AAS) is transmitted in autosomal dominant mode of inheritance.<ref name="pmid63446352">{{cite journal| author=Grier RE, Farrington FH, Kendig R, Mamunes P| title=Autosomal dominant inheritance of the Aarskog syndrome. | journal=Am J Med Genet | year= 1983 | volume= 15 | issue= 1 | pages= 39-46 | pmid=6344635 | doi=10.1002/ajmg.1320150105 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6344635  }}</ref>
 * It is understood that Aarskog-Scott syndrome (AAS) is the result caused by a [[mutation]] in ''[[FGD1 (gene)|FGD1]]'' gene.
-* ''[[FGD1 (gene)|FGD1]]'' gene is located on  X chromosome.
+* ''[[FGD1 (gene)|FGD1]]'' gene mapped to the Xp11.21 region is located on  [[X chromosome]].
-*Normally, in most of the situations males have one X chromosome and females have two X chromosomes.
+*Normally, in most of the situations males have one [[X chromosome]] and females have two [[X chromosome|X chromosomes]].
-*When mutation occurs in ''[[FGD1 (gene)|FGD1]]'' gene of males may result in the Aarskog-Scott syndrome (AAS).
+*When [[Mutations|mutation]] occurs in ''[[FGD1 (gene)|FGD1]]'' gene of males may result in the Aarskog-Scott syndrome (AAS).<ref name="ZouGreenblatt2011">{{cite journal|last1=Zou|first1=Weiguo|last2=Greenblatt|first2=Matthew B.|last3=Shim|first3=Jae-Hyuck|last4=Kant|first4=Shashi|last5=Zhai|first5=Bo|last6=Lotinun|first6=Sutada|last7=Brady|first7=Nicholas|last8=Hu|first8=Dorothy Zhang|last9=Gygi|first9=Steven P.|last10=Baron|first10=Roland|last11=Davis|first11=Roger J.|last12=Jones|first12=Dallas|last13=Glimcher|first13=Laurie H.|title=MLK3 regulates bone development downstream of the faciogenital dysplasia protein FGD1 in mice|journal=Journal of Clinical Investigation|volume=121|issue=11|year=2011|pages=4383–4392|issn=0021-9738|doi=10.1172/JCI59041}}</ref>
-*But, in females the mutation had to occur in both X chromosomes to manifest the disease Aarskog-Scott syndrome (AAS).
+*But, in females the [[mutation]] had to occur in both [[X chromosomes]] to manifest the disease Aarskog-Scott syndrome (AAS).
-*In females if the mutation occurs in only one x chromosome then it results in mild features of Aarskog-Scott syndrome (AAS).
+*In females if the mutation occurs in only one [[X chromosome]] then it results in mild features of Aarskog-Scott syndrome (AAS).
-*The gene ''FGD1'' specifically encodes for guanine nucleotide exchange factor (GEF).
+*The gene ''[[FGD1]]'' specifically encodes for [[Guanine nucleotide exchange factor|guanine nucleotide]] exchange factor ([[Guanine nucleotide exchange factor|GEF]]).<ref name="pmid14560308">{{cite journal| author=Orrico A, Galli L, Cavaliere ML, Garavelli L, Fryns JP, Crushell E et al.| title=Phenotypic and molecular characterisation of the Aarskog-Scott syndrome: a survey of the clinical variability in light of FGD1 mutation analysis in 46 patients. | journal=Eur J Hum Genet | year= 2004 | volume= 12 | issue= 1 | pages= 16-23 | pmid=14560308 | doi=10.1038/sj.ejhg.5201081 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14560308  }}</ref>
-*Guanine nucleotide exchange factor (GEF) inturn activates Cdc42 which belongs to Ras homology of the p21 GTPases.
+*[[Guanine nucleotide exchange factor]] ([[Guanine nucleotide exchange factor|GEF]]) inturn activates Cdc42 which belongs to Ras homology of the p21 GTPases.<ref name="pmid27199457">{{cite journal| author=Pedigo NG, Van Delden D, Walters L, Farrell CL| title=Minireview: Role of genetic changes of faciogenital dysplasia protein 1 in human disease. | journal=Physiol Genomics | year= 2016 | volume= 48 | issue= 7 | pages= 446-54 | pmid=27199457 | doi=10.1152/physiolgenomics.00101.2015 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27199457  }}</ref><ref name="pmid10721717">{{cite journal| author=Pasteris NG, Nagata K, Hall A, Gorski JL| title=Isolation, characterization, and mapping of the mouse Fgd3 gene, a new Faciogenital Dysplasia (FGD1; Aarskog Syndrome) gene homologue. | journal=Gene | year= 2000 | volume= 242 | issue= 1-2 | pages= 237-47 | pmid=10721717 | doi=10.1016/s0378-1119(99)00518-1 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10721717  }}</ref><ref name="pmid16595546">{{cite journal| author=Rajnicek AM, Foubister LE, McCaig CD| title=Temporally and spatially coordinated roles for Rho, Rac, Cdc42 and their effectors in growth cone guidance by a physiological electric field. | journal=J Cell Sci | year= 2006 | volume= 119 | issue= Pt 9 | pages= 1723-35 | pmid=16595546 | doi=10.1242/jcs.02896 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16595546  }}</ref>
-*Upon activation of Cdc42, FGD1 proteins they activate the following:
+*Upon activation of [[CDC42|Cdc42]], [[FGD1]] [[Protein|proteins]] they activate the following:<ref name="pmid10458911">{{cite journal| author=Pasteris NG, Gorski JL| title=Isolation, characterization, and mapping of the mouse and human Fgd2 genes, faciogenital dysplasia (FGD1; Aarskog syndrome) gene homologues. | journal=Genomics | year= 1999 | volume= 60 | issue= 1 | pages= 57-66 | pmid=10458911 | doi=10.1006/geno.1999.5903 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10458911  }}</ref><ref name="pmid10930571">{{cite journal| author=Orrico A, Galli L, Falciani M, Bracci M, Cavaliere ML, Rinaldi MM et al.| title=A mutation in the pleckstrin homology (PH) domain of the FGD1 gene in an Italian family with faciogenital dysplasia (Aarskog-Scott syndrome). | journal=FEBS Lett | year= 2000 | volume= 478 | issue= 3 | pages= 216-20 | pmid=10930571 | doi=10.1016/s0014-5793(00)01857-3 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10930571  }}</ref><ref name="pmid11093277">{{cite journal| author=Schwartz CE, Gillessen-Kaesbach G, May M, Cappa M, Gorski J, Steindl K et al.| title=Two novel mutations confirm FGD1 is responsible for the Aarskog syndrome. | journal=Eur J Hum Genet | year= 2000 | volume= 8 | issue= 11 | pages= 869-74 | pmid=11093277 | doi=10.1038/sj.ejhg.5200553 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11093277  }}</ref><ref name="pmid92686452">{{cite journal| author=Pasteris NG, Buckler J, Cadle AB, Gorski JL| title=Genomic organization of the faciogenital dysplasia (FGD1; Aarskog syndrome) gene. | journal=Genomics | year= 1997 | volume= 43 | issue= 3 | pages= 390-4 | pmid=9268645 | doi=10.1006/geno.1997.4837 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9268645  }}</ref><ref name="pmid16246005">{{cite journal| author=Hall A| title=Rho GTPases and the control of cell behaviour. | journal=Biochem Soc Trans | year= 2005 | volume= 33 | issue= Pt 5 | pages= 891-5 | pmid=16246005 | doi=10.1042/BST20050891 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16246005  }}</ref><ref name="pmid10320936">{{cite journal| author=Ridley AJ, Allen WE, Peppelenbosch M, Jones GE| title=Rho family proteins and cell migration. | journal=Biochem Soc Symp | year= 1999 | volume= 65 | issue=  | pages= 111-23 | pmid=10320936 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10320936  }}</ref><ref name="pmid11509562">{{cite journal| author=Linseman DA, Laessig T, Meintzer MK, McClure M, Barth H, Aktories K et al.| title=An essential role for Rac/Cdc42 GTPases in cerebellar granule neuron survival. | journal=J Biol Chem | year= 2001 | volume= 276 | issue= 42 | pages= 39123-31 | pmid=11509562 | doi=10.1074/jbc.M103959200 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11509562  }}</ref><ref name="pmid10816416">{{cite journal| author=Bishop AL, Hall A| title=Rho GTPases and their effector proteins. | journal=Biochem J | year= 2000 | volume= 348 Pt 2 | issue=  | pages= 241-55 | pmid=10816416 | doi= | pmc=1221060 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10816416  }}</ref><ref name="OrricoGalli2010">{{cite journal|last1=Orrico|first1=A.|last2=Galli|first2=L.|last3=Faivre|first3=L.|last4=Clayton-Smith|first4=J.|last5=Azzarello-Burri|first5=S.M.|last6=Hertz|first6=J.M.|last7=Jacquemont|first7=S.|last8=Taurisano|first8=R.|last9=Arroyo Carrera|first9=I.|last10=Tarantino|first10=E.|last11=Devriendt|first11=K.|last12=Melis|first12=D.|last13=Thelle|first13=T.|last14=Meinhardt|first14=U.|last15=Sorrentino|first15=V.|title=Aarskog-Scott syndrome: Clinical update and report of nine novel mutations of theFGD1gene|journal=American Journal of Medical Genetics Part A|volume=152A|issue=2|year=2010|pages=313–318|issn=15524825|doi=10.1002/ajmg.a.33199}}</ref><ref name="pmid30778386">{{cite journal| author=Egorov M, Polishchuk R| title=Identification of CDC42 Effectors Operating in FGD1-Dependent Trafficking at the Golgi. | journal=Front Cell Dev Biol | year= 2019 | volume= 7 | issue=  | pages= 7 | pmid=30778386 | doi=10.3389/fcell.2019.00007 | pmc=6369352 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30778386  }}</ref>
-**Fibroblasts
+**[[Fibroblasts]]
-**Cytoskeletal elements which are involved in
+**[[Cytoskeletal]] elements which are involved in
-***Cellular signaling
+***[[Cellular signaling]]
-***Adhesion
+***[[Adhesion]]
 ***Migration
-**c- N-terminal kinase (JNK) signaling cascade which involves:
+**c- N-terminal kinase ([[C-Jun N-terminal kinases|JNK]]) signaling cascade which involves:
-***Cell growth
+***[[Cell growth]]
-***Apoptosis
+***[[Apoptosis]]
-***Cellular differentiation
+***Cellular [[differentiation]]
+* These abnormalities of [[FGD1]]/[[CDC42|Cdc42]] signaling pathway may produce an defective [[embryonic]] development and abnormal [[Endochondral ossification|endochondral]] and [[Intramembranous ossification|intramembranous]] bone formation and leads to  Aarskog-Scott syndrome (AAS).
-* These abnormalities of FGD1/Cdc42 signaling pathway may produce an defective embryonic development and abnormal endochondral and intramembranous bone formation and leads to  Aarskog-Scott syndrome (AAS).
 == Causes ==
 ==== Genetic Cause ====
 * Aarskog-Scott syndrome (AAS) is caused by a [[mutation]] in the ''[[FGD1 (gene)|FGD1]]'' gene.
 == Differentiating Aarskog-Scott syndrome from other Diseases ==
+* Aarskog-Scott syndrome (AAS) must be differentiated from [[Robinow syndrome]], [[Noonan syndrome]], [[pseudohypoparathyroidism]], [[Silver-Russell Syndrome|Silver-Russel]]<nowiki/>l and [[SHORT syndrome|SHORT]] syndrome.<ref name="pmid27544718">{{cite journal| author=Parıltay E, Hazan F, Ataman E, Demir K, Etlik Ö, Özbek E et al.| title=A novel splice site mutation of FGD1 gene in an Aarskog-Scott syndrome patient with a large anterior fontanel. | journal=J Pediatr Endocrinol Metab | year= 2016 | volume= 29 | issue= 9 | pages= 1111-4 | pmid=27544718 | doi=10.1515/jpem-2015-0482 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27544718  }}</ref><ref name="Weinstein2016">{{cite journal|last1=Weinstein|first1=Lee S.|title=GNAS and McCune-Albright/Fibrous Dysplasia, Albright Hereditary Osteodystrophy, and Pseudohypoparathyroidism|year=2016|pages=1178–1181|doi=10.1093/med/9780199934522.003.0179}}</ref><ref name="Reza JabalameliBriceno20164">{{cite journal|last1=Reza Jabalameli|first1=M.|last2=Briceno|first2=Ignacio|last3=Martinez|first3=Julio|last4=Briceno|first4=Ignacio|last5=J. Pengelly|first5=Reuben|last6=Ennis|first6=Sarah|last7=Collins|first7=Andrew|title=Aarskog-Scott syndrome: phenotypic and genetic heterogeneity|journal=AIMS Genetics|volume=3|issue=1|year=2016|pages=49–59|issn=2377-1143|doi=10.3934/genet.2016.1.49}}</ref>
 == Epidemiology and Demographics ==
+===Incidence===
+*The [[incidence]] of Aarskog-Scott syndrome (AAS) is unknown.<ref name="Reza JabalameliBriceno20162">{{cite journal|last1=Reza Jabalameli|first1=M.|last2=Briceno|first2=Ignacio|last3=Martinez|first3=Julio|last4=Briceno|first4=Ignacio|last5=J. Pengelly|first5=Reuben|last6=Ennis|first6=Sarah|last7=Collins|first7=Andrew|title=Aarskog-Scott syndrome: phenotypic and genetic heterogeneity|journal=AIMS Genetics|volume=3|issue=1|year=2016|pages=49–59|issn=2377-1143|doi=10.3934/genet.2016.1.49}}</ref>
+*Till now there are 29 cases of Aarskog-Scott syndrome (AAS) had been diagnosed worldwide.
+=== Prevalence===
+*The [[prevalence]] of Aarskog-Scott syndrome (AAS) is 1/25 000 worldwide.<ref name="pmid25227149">Orrico A, Galli L, Clayton-Smith J, Fryns JP (2015) [https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=25227149 Clinical utility gene card for: Aarskog-Scott Syndrome (faciogenital dysplasia) - update 2015.] ''Eur J Hum Genet'' 23 (4):. [http://dx.doi.org/10.1038/ejhg.2014.178 DOI:10.1038/ejhg.2014.178] PMID: [https://pubmed.gov/25227149 25227149]</ref>
+*The [[prevalence]] of Aarskog-Scott syndrome (AAS) is 1-9 per 1,000,000 in Europe.
+=== Age===
+*Aarskog-Scott syndrome (AAS) commonly affects individuals of younger age especially in childwood.
+===Race===
+*There is no [[racial]] predilection to Aarskog-Scott syndrome (AAS).
+=== Gender===
+*Aarskog-Scott syndrome (AAS) affects men more commonly than in women.<ref name="Reza JabalameliBriceno2016">{{cite journal|last1=Reza Jabalameli|first1=M.|last2=Briceno|first2=Ignacio|last3=Martinez|first3=Julio|last4=Briceno|first4=Ignacio|last5=J. Pengelly|first5=Reuben|last6=Ennis|first6=Sarah|last7=Collins|first7=Andrew|title=Aarskog-Scott syndrome: phenotypic and genetic heterogeneity|journal=AIMS Genetics|volume=3|issue=1|year=2016|pages=49–59|issn=2377-1143|doi=10.3934/genet.2016.1.49}}</ref>
 == Risk Factors ==
+There are no established [[risk factors]] for Aarskog-Scott syndrome (AAS).
 == Screening ==
+There is insufficient evidence to recommend routine [[Screening (medicine)|screening]] for Aarskog-Scott syndrome (AAS).
 == Natural History, Complications and Prognosis ==
+=== Natural History ===
+* The [[symptoms]] of Aarskog-Scott syndrome (AAS) usually develop in the first decade of life, and start with symptoms such as delayed [[Growth spurts|growth spurt]].
+* The [[symptoms]] of  Aarskog-Scott syndrome (AAS) typically develop in 2 to 4 years of age.
+=== Complications ===
+* Common complications of Aarskog-Scott syndrome (AAS) include:<ref name="JogiyaSandy2009">{{cite journal|last1=Jogiya|first1=Aryan|last2=Sandy|first2=Charles|title=Mild Optic Nerve Hypoplasia with Retinal Venous Tortuosity in Aarskog (Facial-Digital-Genital) Syndrome|journal=Ophthalmic Genetics|volume=26|issue=3|year=2009|pages=139–141|issn=1381-6810|doi=10.1080/13816810500229025}}</ref><ref name="pmid7953251">{{cite journal| author=Pizio HF, Scott MH, Richard JM| title=Tortuosity of the retinal vessels in Aarskog syndrome (faciogenital dysplasia). | journal=Ophthalmic Genet | year= 1994 | volume= 15 | issue= 1 | pages= 37-40 | pmid=7953251 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7953251  }}</ref><ref name="pmid63446353">{{cite journal| author=Grier RE, Farrington FH, Kendig R, Mamunes P| title=Autosomal dominant inheritance of the Aarskog syndrome. | journal=Am J Med Genet | year= 1983 | volume= 15 | issue= 1 | pages= 39-46 | pmid=6344635 | doi=10.1002/ajmg.1320150105 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6344635  }}</ref>
+**[[Cryptorchidism]]
+**[[Spina bifida occulta]]
+**[[Cervical spine]] abnormalities
+**[[Scoliosis]]
+**[[Camptodactyly]]
+**[[Lymphoedema]]
+**[[Optic nerve]] [[hypoplasia]]
+**[[Retinal]] vessel [[tortuosity]]
+=== Prognosis ===
+*[[Prognosis]] is generally good with Aarskog-Scott syndrome (AAS) patients.
 == Diagnostic study of choice ==
+* Aarskog-Scott syndrome (AAS) is primarily diagnosed based on clinical presentation based on Teebi criteria which includes:<ref name="pmid28209013">{{cite journal| author=Ahmed A, Mufeed A, Ramachamparambathu AK, Hasoon U| title=Identifying Aarskog Syndrome. | journal=J Clin Diagn Res | year= 2016 | volume= 10 | issue= 12 | pages= ZD09-ZD11 | pmid=28209013 | doi=10.7860/JCDR/2016/22180.8982 | pmc=5296586 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28209013  }}</ref><ref name="pmid63446354">{{cite journal| author=Grier RE, Farrington FH, Kendig R, Mamunes P| title=Autosomal dominant inheritance of the Aarskog syndrome. | journal=Am J Med Genet | year= 1983 | volume= 15 | issue= 1 | pages= 39-46 | pmid=6344635 | doi=10.1002/ajmg.1320150105 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6344635  }}</ref><ref name="pmid14594174">{{cite journal| author=Darendeliler F, Larsson P, Neyzi O, Price AD, Hagenäs L, Sipilä I et al.| title=Growth hormone treatment in Aarskog syndrome: analysis of the KIGS (Pharmacia International Growth Database) data. | journal=J Pediatr Endocrinol Metab | year= 2003 | volume= 16 | issue= 8 | pages= 1137-42 | pmid=14594174 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14594174  }}</ref><ref name="pmid145603082">{{cite journal| author=Orrico A, Galli L, Cavaliere ML, Garavelli L, Fryns JP, Crushell E et al.| title=Phenotypic and molecular characterisation of the Aarskog-Scott syndrome: a survey of the clinical variability in light of FGD1 mutation analysis in 46 patients. | journal=Eur J Hum Genet | year= 2004 | volume= 12 | issue= 1 | pages= 16-23 | pmid=14560308 | doi=10.1038/sj.ejhg.5201081 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14560308  }}</ref>
+**[[Short stature]]
+**[[Hypertelorism]]
+**Fold of the lower lip
+**[[Brachydactyly]]
+**Interdigital webbing
+**[[Shawl scrotum]]
+**Long [[philtrum]]
+**Mild facial [[hypoplasia]]
+[[File:Aarskog syndrome.jpg|alt=Aarskog syndrome|thumb|Patients with clinical features of Aarskog syndrome-(A) Patient 1; note distinctive facial characteristics and interdigital tracts in both hands. (B) Patient 2; discrete facial features and the shawl scrotum can be appreciated. (C) Patient 3 and his mother (patient 8); note prominent forehead, widow's peak, hypertelorism, and fold under the lower lip. (D) Patient 4 with widow's peak, midface hypoplasia, ptosis, clinodactyly, and brachydactyly. (E) Patient 5, brother of patient 4, with distinctive facial features, clinodactyly, and brachydactyly. Case courtesy by Mariana Pérez-Coria et al<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4444161/|title=Identification of novel mutations in Mexican patients with Aarskog–Scott syndrome|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref>]]
 == History and Symptoms ==
+=== Common Symptoms ===
+Common symptoms of Aarskog-Scott syndrome (AAS) include:<ref name="pmid11093277" /><ref name="pmid24637303">{{cite journal| author=Şıklar Z, Berberoğlu M| title=Syndromic disorders with short stature. | journal=J Clin Res Pediatr Endocrinol | year= 2014 | volume= 6 | issue= 1 | pages= 1-8 | pmid=24637303 | doi=10.4274/Jcrpe.1149 | pmc=3986733 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24637303  }}</ref>
+*[[Short stature]] (evident by 1-3 years of age)
+*[[Mental retardation]]
+*[[Hypertelorism]]
+*[[Umbilical hernia]]
+*[[Shawl scrotum]]
+*[[Hypospadias]]
+*Undescended [[testes]]
 == Physical Examination ==
+==== HEENT ====
+[[Facial]] features are very prominent and important for the diagnosis of Aarskog-Scott syndrome (AAS) which include:<ref name="Reza JabalameliBriceno20163">{{cite journal|last1=Reza Jabalameli|first1=M.|last2=Briceno|first2=Ignacio|last3=Martinez|first3=Julio|last4=Briceno|first4=Ignacio|last5=J. Pengelly|first5=Reuben|last6=Ennis|first6=Sarah|last7=Collins|first7=Andrew|title=Aarskog-Scott syndrome: phenotypic and genetic heterogeneity|journal=AIMS Genetics|volume=3|issue=1|year=2016|pages=49–59|issn=2377-1143|doi=10.3934/genet.2016.1.49}}</ref><ref name="pmid19110080">{{cite journal| author=Bedoyan JK, Friez MJ, DuPont B, Ahmad A| title=First case of deletion of the faciogenital dysplasia 1 (FGD1) gene in a patient with Aarskog-Scott syndrome. | journal=Eur J Med Genet | year= 2009 | volume= 52 | issue= 4 | pages= 262-4 | pmid=19110080 | doi=10.1016/j.ejmg.2008.12.001 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19110080  }}</ref><ref name="pmid8322809">{{cite journal| author=Teebi AS, Rucquoi JK, Meyn MS| title=Aarskog syndrome: report of a family with review and discussion of nosology. | journal=Am J Med Genet | year= 1993 | volume= 46 | issue= 5 | pages= 501-9 | pmid=8322809 | doi=10.1002/ajmg.1320460508 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8322809  }}</ref><ref name="UlaşGiampietro2014">{{cite journal|last1=Ulaş|first1=Cıkla|last2=Giampietro|first2=Philip F.|last3=Sadighi|first3=Alireza|last4=Başkaya|first4=Mustafa K.|title=Ruptured Posterior Communicating Artery Aneurysm Associated with Aarskog Syndrome|journal=NMC Case Report Journal|volume=2|issue=3|year=2014|pages=85–87|issn=2188-4226|doi=10.2176/nmccrj.2014-0022}}</ref><ref name="pmid282090132">{{cite journal| author=Ahmed A, Mufeed A, Ramachamparambathu AK, Hasoon U| title=Identifying Aarskog Syndrome. | journal=J Clin Diagn Res | year= 2016 | volume= 10 | issue= 12 | pages= ZD09-ZD11 | pmid=28209013 | doi=10.7860/JCDR/2016/22180.8982 | pmc=5296586 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28209013  }}</ref>
+* Round face
+*Facial [[edema]] with downward slanting [[palpebral fissures]]
+*Short [[nose]] along with [[Anteverted nostrils|anteverted]] [[nares]]
+*Long [[philtrum]]
+*Ocular [[hypertelorism]] with [[ptosis]]
+*Maxillary [[hypoplasia]]
+*A broad upper [[lip]] with a crease below the lower [[lip]]
+*Abnormal auriculares
+==== Neck ====
+* Short [[neck]]
+* Webbing of sides of the [[neck]]
+==== Chest ====
+* Mild [[pectus excavatum]] (sunken [[chest]])
+==== Abdomen ====
+* Protruding [[navel]]
+*[[Inguinal hernias]]
+==== Genitourinary ====
+*[[Shawl Scrotum]]<ref name="pmid282090133">{{cite journal| author=Ahmed A, Mufeed A, Ramachamparambathu AK, Hasoon U| title=Identifying Aarskog Syndrome. | journal=J Clin Diagn Res | year= 2016 | volume= 10 | issue= 12 | pages= ZD09-ZD11 | pmid=28209013 | doi=10.7860/JCDR/2016/22180.8982 | pmc=5296586 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28209013  }}</ref>
+* Undescended [[testicles]]
+==== Extremities ====
+*Small, broad [[hands]] and [[feet]]
+* Short fingers and toes ([[brachydactyly]])
+*[[Clinodactyly]]
+* Mild webbing between the [[Finger|fingers]] and [[Toe|toes]]
+*[[Simian crease]]
+* Broad [[Thumb|thumbs]] and big [[Toe|toes]]
 == Laboratory Findings ==
+* There are no [[diagnostic]] laboratory findings associated with Aarskog-Scott syndrome (AAS).
 == Electrocardiogram ==
+* There are no [[The electrocardiogram|ECG]] findings associated with Aarskog-Scott syndrome (AAS).
 == X-Ray Findings ==
+*[[File:Aarskog-Scott syndrome X-ray.jpg|thumb|Scoliosis- a) Early postoperative X-ray (b) 10 years follow-up X-ray.Case courtesy Kerim Sariyilmaz<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634118/|title=Aarskog-Scott syndrome: An unusual cause of scoliosis|last=|first=|date=|website=|archive-url=|archive-date=|dead-url=|access-date=}}</ref>|alt=Scoliosis]]There are no [[X-rays|x-ray]] findings associated with Aarskog-Scott syndrome (AAS). However, an x-ray may be helpful in the diagnosis of [[complications]] of Aarskog-Scott syndrome (AAS), which include:<ref name="pmid29021683">{{cite journal| author=Sariyilmaz K, Ozkunt O, Korkmaz M, Dikici F, Domanic U| title=Aarskog-Scott syndrome: An unusual cause of scoliosis. | journal=J Craniovertebr Junction Spine | year= 2017 | volume= 8 | issue= 3 | pages= 283-284 | pmid=29021683 | doi=10.4103/jcvjs.JCVJS_133_16 | pmc=5634118 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29021683  }}</ref><ref name="pmid10906777">{{cite journal| author=Gorski JL, Estrada L, Hu C, Liu Z| title=Skeletal-specific expression of Fgd1 during bone formation and skeletal defects in faciogenital dysplasia (FGDY; Aarskog syndrome). | journal=Dev Dyn | year= 2000 | volume= 218 | issue= 4 | pages= 573-86 | pmid=10906777 | doi=10.1002/1097-0177(2000)9999:9999<::AID-DVDY1015>3.0.CO;2-F | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10906777  }}</ref><ref name="pmid282090134">{{cite journal| author=Ahmed A, Mufeed A, Ramachamparambathu AK, Hasoon U| title=Identifying Aarskog Syndrome. | journal=J Clin Diagn Res | year= 2016 | volume= 10 | issue= 12 | pages= ZD09-ZD11 | pmid=28209013 | doi=10.7860/JCDR/2016/22180.8982 | pmc=5296586 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28209013  }}</ref>
+**[[Skeletal]] abnormalities
+**[[Tooth]] abnormalities
+**[[Scoliosis]]
 == Echocardiography and Ultrasound ==
+* The [[ultrasound]] can help in detecting the undescended [[testis]] associated with Aarskog-Scott syndrome (AAS).<ref name="pmid22152893">{{cite journal| author=Tasian GE, Copp HL, Baskin LS| title=Diagnostic imaging in cryptorchidism: utility, indications, and effectiveness. | journal=J Pediatr Surg | year= 2011 | volume= 46 | issue= 12 | pages= 2406-13 | pmid=22152893 | doi=10.1016/j.jpedsurg.2011.08.008 | pmc=3712862 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22152893  }}</ref>
 == CT-Scan Findings ==
+*[[Head]] [[Computed tomography|CT scan]] may be helpful in the diagnosis of Aarskog-Scott syndrome (AAS). Findings on [[Computed tomography|CT scan]] suggestive Aarskog-Scott syndrome (AAS) include:
+**[[Cystic]] development
 == MRI Findings ==
+* There are no [[Magnetic resonance imaging|MRI]] findings associated with Aarskog-Scott syndrome (AAS).
-== Other Imaging Findings ==
-== Other Diagnostic Studies ==
 == Medical Therapy ==
+* There is no treatment for Aarskog-Scott syndrome (AAS); the mainstay of therapy is [[symptomatic]] care.
+*Patients with [[short stature]] are treated with [[growth hormone]], which shows promising results in increasing the height of the patients.<ref name="pmid29280742">{{cite journal| author=Deodati A, Cianfarani S| title=The Rationale for Growth Hormone Therapy in Children with Short Stature. | journal=J Clin Res Pediatr Endocrinol | year= 2017 | volume= 9 | issue= Suppl 2 | pages= 23-32 | pmid=29280742 | doi=10.4274/jcrpe.2017.S003 | pmc=5790327 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29280742  }}</ref><ref name="pmid20631818">{{cite journal| author=Frindik JP, Kemp SF| title=Managing idiopathic short stature: role of somatropin (rDNA origin) for injection. | journal=Biologics | year= 2010 | volume= 4 | issue=  | pages= 147-55 | pmid=20631818 | doi= | pmc=2898102 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20631818  }}</ref>
 == Interventions ==
+* There are some recommended [[therapeutic]] interventions for the management of Aarskog-Scott syndrome (AAS), which includes speech [[pathologists]], [[audiologists]] and eye specialists who can improve the quality of the patient's life.
 == Surgery ==
+*[[Surgery]] is usually reserved for patients with [[congenital]] or structural [[malformations]] which involves the following:
+**[[Hypospadias]](opening of the [[penis]] is on the underside rather than the tip)
+**[[Inguinal hernia|Inguinal]] or [[umbilical]] [[hernias]]
+**[[Cryptorchidism]](undescended [[Testicle|testis]])
 == Primary Prevention ==
+* There are no established measures for the [[primary prevention]] of Aarskog-Scott syndrome (AAS).
 == Secondary Prevention ==
+* There are no established measures for the [[secondary prevention]] of Aarskog-Scott syndrome (AAS).
-== Cost-Effectiveness of Therapy ==
+== References ==
-== Future or Investigational Therapies ==
-== Genetic ==
-[[Image:XlinkRecessive.jpg|thumb|left|180px|X-linked recessive inheritance.]]
-Aarskog-Scott syndrome is transmitted in an [[X-linked recessive]] manner. The sons of female carriers are at 50% risk of being affected with the syndrome. The daughters of female carriers are at 50% risk of being carriers themselves. Females may have mild manifestations of the syndrome. The syndrome is caused by [[mutation]] in a [[gene]] called FGDY1 in band p11.21 on the [[X chromosome]].
-==Eponym==
-The syndrome is named for Dagfinn Aarskog, a Norwegian pediatrician and human geneticist who first described it in 1970, and for Charles I. Scott, Jr., an American medical geneticist who independently described the syndrome in 1971.
-==Description==
-The Aarskog-Scott syndrome is a disorder with short stature, [[hypertelorism]], downslanting [[palpebral fissure]]s, anteverted nostrils, joint laxity, shawl scrotum, and mental retardation. The physical [[phenotype]] varies with age and postpuberal males may have only minor remnant manifestations of the prepuberal phenotype.
-==Frequent features==
-*Growth
-** mild to moderate short stature evident by 1-3 years of age
-** delayed adolescent growth spurt
-*Performance
-** slight (dull normal) to moderate mental deficiency
-** hyperactivity and attention deficit
-** social performance usually good
-*Face
-** rounded face
-** [[widow's peak]] hairline
-** wide-set eyes ([[hypertelorism]])
-** droopy eyelids ([[blepharoptosis]])
-** downslanting eye slits ([[palpebral fissure]]s)
-** small nose with nostrils tipped forward (anteverted)
-** underdeveloped mid-portion of the face ([[maxilla]]
-** wide groove above the upper lip (broad [[philtrum]])
-** crease below the lower lip
-** delayed eruption of [[teeth]]
-** top portion (upper helix) of the ear folded over slightly
-*Hands and feet
-** small, broad hands and feet
-** short fingers and toes ([[brachydactyly]])
-** in-curving of the 5th finger (clinodactyly)
-** mild webbing between the fingers and toes
-** single transverse "[[simian crease]]" in palm
-** broad thumbs and big toes
-*Neck
-** short neck
-** webbing of sides of the neck
-*Chest
-** mild [[pectus excavatum]] (sunken chest)
-*Abdomen
-** protruding [[navel]]
-** [[inguinal hernia]]s
-*Genitalia
-** [[Shawl Scrotum]]
-** undescended testicles
-==Diagnosis==
-[[Genetic testing]] may be available for mutations in the FGDY1 gene.  [[Genetic counseling]] is indicated for individuals or families who may carry this condition, as there are overlapping features with [[Fetal alcohol syndrome]].
-==Treatment==
-[[Surgery]] may be required to correct some of the anomalies, and [[orthodontic]] treatment may be used to correct some of the facial abnormalities. Trials of [[growth hormone]] have not been effective to treat short stature in this disorder.
-==Support Group==
-The MAGIC Foundation for Children's Growth is a support group for Aarskog-Scott syndrome and can be found at [http://www.magicfoundation.org www.magicfoundation.org].
-==Prognosis==
-Mild degrees of mental slowness may be present, but affected children usually have good social skills. Some males may exhibit reduced fertility.
-==Complications==
-Some recent findings have included cystic changes in the brain and generalized [[seizure]]s. There may be difficulty growing in the first year of life in up to one-third of cases. Misaligned teeth may require orthodontic correction. An undescended testicle will require surgery.
-==Molecular biology==
-The Aarskog-Scott syndrome is due to mutation in the [[FGD1]] gene. FGD1 encodes a [[guanine nucleotide exchange factor]] (GEF) that specifically activates [[Cdc42]], a member of the [[Rho GTP-binding protein|Rho]] (Ras homology) family of the p21 [[GTPase]]s. By activating Cdc42, FGD1 [[protein]] stimulates [[fibroblast]]s to form filopodia, cytoskeletal elements involved in cellular signaling, adhesion, and migration. Through Cdc42, FGD1 protein also activates the [[c-Jun N-terminal kinase]] (JNK) signaling cascade, a pathway that regulates cell growth, [[apoptosis]], and cellular differentiation.
-Within the developing mouse skeleton, FGD1 protein is expressed in precartilaginous mesenchymal condensations, the [[perichondrium]] and periostium, proliferating [[chondrocyte]]s, and [[osteoblast]]s. These results suggest that FGD1 signaling may play a role in the biology of several different skeletal cell types including mesenchymal prechondrocytes, chondrocytes, and osteoblasts. The characterization of the spatiotemporal pattern of FGD1 expression in mouse embryos has provided important clues to the understanding of the [[pathogenesis]] of Aarskog-Scott syndrome.
 [[Category:Genetic disorders]]
 [[Category:Pediatrics]]
@@ Line 189: / Line 171: @@
 [[pl:Zespół Aarskoga]]
 [[pt:Síndrome de Aarskog]]
-It appears likely that the primary defect in Aarskog-Scott syndrome is an abnormality of FGD1/Cdc42 signaling resulting in anomalous [[embryonic development]] and abnormal endochondral and intramembranous bone formation
-==References==
 {{Reflist|2}}
 {{WH}}
 {{WS}}
 [[Category: Rare diseases]]