Aarskog-Scott syndrome

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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

Causes

Genetic Cause

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

Differentiating Aarskog-Scott syndrome from other Diseases

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

Prognosis

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

Diagnostic study of choice

Aarskog syndrome
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]

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]

Neck

Chest

Abdomen

Genitourinary

Extremities

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
    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]

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:

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

Primary Prevention

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

Secondary Prevention

References

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