Aarskog-Scott syndrome

What is Aarskog-Scott syndrome?

Aarskog-Scott syndrome is a rare genetic disorder that occurs mainly in males due to the way in which it is inherited.

It is often first identified from the age of 3 years old, when restricted growth prompts a diagnosis.

The defining features of this rare disease include a short stature, unique facial features, as well as abnormalities affecting the skeleton and genitalia of affected individuals.

This syndrome is also known as:
Aarskog Syndrome; X-linked Facio-digito-genital syndrome; Faciodigitogenital Syndrome; Faciogenital Dysplasia; Fgdy

What gene change causes Aarskog-Scott syndrome?

Mutations on the FGD1 gene cause the syndrome.

It is an X-linked inherited disorder, making it much more common in males than females who display less severe symptoms.

The syndrome appears to be inherited in either an autosomal dominant or autosomal recessive pattern.

Syndromes inherited in an X-linked recessive pattern generally only affect males. Males only have one X chromosome, and so one copy of a gene mutation on it causes the syndrome. Females, with two X chromosomes, only one of which will be mutated, are not likely to be affected.


With syndromes inherited in an X-linked dominant pattern, a mutation in just one of the copies of the gene, causes the syndrome. This can be in one of the female X chromosomes, and in the one X chromosomes males have. Males tend to have more severe symptoms than females.

what are the main symptoms of Aarskog-Scott syndrome?

The main symptoms of the syndrome include growth restriction in childhood, although by puberty most individuals have caught up with their growth.

Unique facial characteristics of the syndrome include a small nose, a large distance between the eyes, a broad forehead, drooping eyelids, webbing between the fingers and short fingers.

Other health conditions associated with the syndrome include a cleft lip or palate, heart defects and genital abnormalities. There is also documentation of neurobehavioral abnormalities. Symptoms may vary considerably between individuals.

Possible clinical traits/features:
Cleft palate, Cervical spine hypermobility, Wide nasal bridge, Broad foot, Broad palm, Attention deficit hyperactivity disorder, X-linked recessive inheritance, Prominent umbilicus, Scoliosis, Radial deviation of finger, Short palm, Broad philtrum, Round face, Clinodactyly, Ptosis, Strabismus, Pectus excavatum, Inguinal hernia, Intellectual disability, Mild short stature, Short nose, Anteverted nares, Growth abnormality, Hyperextensibility of the finger joints, Hypertelorism, Hypermetropia, Hypoplasia of the maxilla, Short foot, Hypoplasia of the odontoid process, Hypodontia, Large earlobe, Syndactyly, Single transverse palmar crease, Widow's peak, Shawl scrotum, Short neck, Delayed puberty, Failure to thrive, Decreased fertility, Curved linear dimple below the lower lip, Cryptorchidism, Downslanted palpebral fissures, Cleft upper lip, Brachydactyly.

How does someone get tested for Aarskog-Scott syndrome?

The initial testing for Aarskog-Scott syndrome can begin with facial analysis screening, through the FDNA Telehealth telegenetics platform, which can identify the key markers of the syndrome and outline the need for further testing. A consultation with a genetic counselor and then a geneticist will follow.

Based on this clinical consultation with a geneticist, the different options for genetic testing will be shared and consent will be sought for further testing.

Medical information on Aarskog-Scott syndrome

Aarskog (1970) reported three males in a single family with short stature, hypertelorism, ptosis, a round face, small hands and feet and a shawl scrotum. The other facial features consist of a broad forehead, downward slanting palpebral fissures, a short snub nose and a long philtrum. A widow's peak is common as well as a frontal cowlick. The facial features may change with age, with hypertelorism becoming less obvious, the forehead becoming less prominent, and the face becoming elongated. The scrotum might be clearly bifid, with a scrotal fold encircling the base of the penis. Short stature is usually between the 3rd and 10th centiles in males, limb shortening may be rhizomelic, and bone age is delayed. There may be catch up growth in late puberty. The trunk looks relatively long. Intellectual disability is present in only a minority of cases and is seldom severe. Other useful signs are joint laxity, mild skin syndactyly, splayed toes with bulbous tips, delayed bone age and occasionally hypoplastic terminal phalanges. Cryptorchidism and inguinal hernia are present in about 50% of cases.
Fernandez et al. (1994) reported ten cases from three Japanese families. Two of these cases had a congenital heart defect (pulmonary stenosis and a VSD). The diagnosis is difficult because a shawl scrotum is not uncommon. Friedman (1985) and Tsukahara and Fernandez (1994) provide learned discussions on the shape of the umbilicus in this syndrome. The appearance is described as prominent or protruding and surrounded by a deep ovoid depression. Focal polymicrogyria can be a feature (Bottani et al., 2007). Occasional patients have had severe club feet and electrical evidence of a myopathy (Al-Semari et al., 2013). Most cases have been males and transmission can occur through unaffected females. However male to male transmission has been reported (Grier et al., 1983). Meschede et al. (1996) reported an adult male with infertility who was shown to produce sperm with abnormal acrosomes. Bawle et al. (1984) reported a fully affected mother and her son. They both carried a balanced X-autosome translocation with breakpoints on the X at Xq13. Guion-Almeida and Richieri-Costa (1992) reported an affected male whose parents were first cousins (but see Teebi (1988) for an autosomal recessive Aarskog-like syndrome). Fryns and Devriendt (1996) suggested that the mother and daughter reported by Teebi et al. (1995) have Aarskog syndrome. Kodama et al. (1981) reported a possible case with growth hormone deficiency. The patient reported by Volter et al., (2014) had ""extreme craniofacial dysplasia"" and had an ectopic tooth in the nasal cavity. The mother and maternal grandmother also had a FGD1 mutation and only had ptosis.

Pasteris et al. (1994) identified the gene causing Aarskog syndrome. It is a Rho/Rac guanine nucleotide exchange factor designated FGD1. Further mutations were reported by Schwartz et al. (2000) and in a series of 46 patients reported by Orrico et al. (2004) there was a 19.5% detection rate. Bedoyan et al. (2009) reported a deletion. Orrico et al. (2005) described an atypical case with borderline intelligence and attention deficit hyperactivity disorder, who had a R408Q mutation inherited from his mother. Another molecularly proven familial case, one with Asperger syndrome and the other with ADHD, was reported by Kaname et al. (2006). A case (c.945insC) mutation reported by Orrico et al. (2007) had a particularly severe phenotype. Further mutations were reported by Orrico et al. (2010).
Griffin et al. (2016) reported a novel FGD1 mutation (predicted to truncate the FGD1 protein at the second to last amino acid of the carboxy-terminal pleckstrin homology (PH) domain) in a family with multiple relatives showing atypical skeletal features including congenital bilateral upper and lower limb joint contractures (clubfoot and flexion contractures of the fingers).

* This information is courtesy of the L M D.

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