Acknowledgement of Aarskog-Scott Syndrome has not been added yet.

Aarskog-Scott syndrome is a rare disease estimated to occur in about 1 in 25,000 people. However, this is considered a low estimation due to the wide range of physical characteristics that people with this syndrome express, and thus difficulty in identifying cases for genetic diagnosis. AAS is more common in people assigned male at birth than female. About 60 cases of AAS have been identified based on the presence of a FGD1 genetic mutation.

Name	Abbreviation
Aarskog Disease	AD
Faciodigitogenital syndrome
Faciogenital dysplasia	FGDY

About 22% of total cases of Aarskog-Scott syndrome are caused by an X-linked genetic disease caused by a mutation in the FGD1 gene. There are no other known causes of AAS at this time, probably due to lack of genetic testing for a majority of diagnosed cases. 

Humans have 23 pairs of chromosomes, with one of each pair inherited from both parents at birth. The 23rd chromosome pair is called the sex chromosome, because they vary depending on the assigned sex of the baby at birth. People assigned male at birth have an X chromosome from their mother and a Y chromosome from their father, while people assigned female at birth have two X chromosomes from their mother and father (the names indicate the shape of the chromosomes). Sex-linked genetic disorders can arise when a mutation is present on one chromosome, often the X chromosome, without a normal copy present on a matching chromosome. Thus, males express the mutant form of the gene only, while females carry the mutant form in one X chromosome but often express the non-mutant form contributed by the other X chromosome.

The FGD1 gene stands for faciogenital dysplasia 1 gene, which encodes a protein that acts as an activator for another gene, Cdc42. This gene encodes a protein that is responsible for signaling different development events to take place in the body, in particular bone development. Without a fully functional gene for FGD1, this process of development cannot properly begin, and thus developmental abnormalities appear that are characteristic of Aarskog-Scott syndrome.

 

Aarskog-Scott syndrome is a rare disease that causes a form of skeletal dysplasia, meaning abnormal development of certain parts of the body due to genetic mutations affecting the bones. This disorder often occurs in people assigned male at birth, and while there are many features that vary from person to person, there are distinct characteristics that can be used to determine an Aarskog-Scott syndrome diagnosis:

1. Facial features: rounded face, broad forehead, wide space between the eyes (ocular hypertelorism), drooping eyelids, smaller nose with outward flared nostrils (anteverted nares), underdeveloped jaw bone (maxilliary hypoplasia), widow’s peak, long upper lip, broadened bridge of the nose

1. Less common: eye abnormalities such as crossed eyes, farsightedness, paralysis of certain muscles in the eye

2. Ear features: low-set ears, thick and fleshy earlobes

3. Dental features: missing teeth at birth, delayed growth of teeth, underdevelopment of enamel around the outside of the tooth (enamel hypoplasia)

1. Less common: incomplete closure of the roof of the mouth or upper lip (cleft palate or lip)

4. Stature features: shortened height, broad and short hands and feet, short and stubby fingers (brachydactyly), permanently bent pinky finger (clinodactyly), highly extendible finger joints, wide and flat feet with larger toes

5. Midsection features: sunken chest, protruding belly and navel due to large intestine invading into abnormal opening in the abdominal muscular lining, incomplete closure of the bones of the spinal column (spina bifida occulta), fusion of upper bones in spinal column (cervical vertebrae)

6. Genital features: abnormal fold of skin at the base of the penis, failure of one or both testes to descend (cryptorchidism), urinary opening located on the underside of the penis

Behavior and learning disorders have been described in some individuals with Aarskog-Scott syndrome, but it is not a consistent feature. Children assigned male at birth with the disorder may present as hyperactive, attention deficit, and impulsive, common symptoms of ADHD.

Other complications that can result from Aarskog-Scott syndrome developmental abnormalities can include failure to gain weight and grow at expected rate, congenital heart defects, and abnormal curvature of the spine (scoliosis).

 

The physical abnormalities or developmental differences associated with Aarskog-Scott syndrome are often the first sign to seek diagnosis of this rare disease. The characteristic features, combined with genetic and family history, provide sufficient information to diagnose Aarskog-Scott syndrome.

 

To confirm a diagnosis of Aaskarg-Scott syndrome, a genetic test to confirm a mutated gene must be conducted. If an individual has characteristic physical traits of AAS, a mutation in the FGD1 gene confirms that they have Aaskarg-Scott syndrome. If they don’t have a mutation in this gene, other genes may be tested for a mutation as they are associated with similar physical traits: ROR2, WNT5A, PIK3R1, SRCAP, KMT2D, KDM6A, SHOX, CUL7.

 

Treatment options for young children, often assigned male at birth, with Aarskog-Scott syndrome often depend on the symptoms experienced by the individual. It is recommended to consult with pediatricians and specialists to treat and/or correct certain physical features that may cause difficulties. This includes testing of hearing and vision to prevent certain facial abnormalities from impairing these abilities. Surgery may be recommended in certain extreme cases of structural abnormalities that lower quality of life. Treatments with growth hormones have been shown to improve height increase in some children with Aarskog-syndrome. It is also common for individuals with AAS to grow to a more average height during puberty.

While development milestones may be delayed and physical features may be abnormal, many individuals with Aarskog-Scott syndrome live healthy lives. Some may experience intellectual disabilities, but this is not a common symptom of this rare disease. Still others may experience complications due to their abnormal bone development, and should be regularly monitored by a doctor to ensure healthy growth. Due to genitalia abnormalities, some people assigned male at birth may experience fertility problems.

 

Tips or Suggestions of Aarskog-Scott Syndrome has not been added yet.

1. https://rarediseases.org/rare-diseases/aarskog-syndrome/

2. Jones KL, ed. Smith’s Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, PA: W. B. Saunders Co.;1997:128-29.

3. Orrico A, Galli L, Clayton-Smith J and Fryns J-P: Clinical utility gene card for: Aarskog–Scott Syndrome (faciogenital dysplasia) – update 2015. Eur J Hum Genet. 2015 Apr; 23(4).

4.     https://www.news-medical.net/health/Aarskog-Syndrome-Causes-and-Diagnosis.aspx

5. https://medlineplus.gov/genetics/gene/fgd1/

6. https://medlineplus.gov/genetics/condition/aarskog-scott-syndrome/

7. https://www.mountsinai.org/health-library/diseases-conditions/aarskog-syndrome