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.

• 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]

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

• 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).

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

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

• 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.

• 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.

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

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

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

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

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

• 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.

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

• 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

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

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

• Short neck
• Webbing of sides of the neck

• Mild pectus excavatum (sunken chest)

• Protruding navel
• Inguinal hernias

• Shawl Scrotum^[53]
• Undescended testicles

• 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

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

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

• 

  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

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

• 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

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

• 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]

• 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 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)

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

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