Aarskog syndrome
Aarskog syndrome is a rare genetic disorder primarily affecting males, characterized by distinctive changes in the size and shape of bones and cartilage, particularly in the face, fingers, and toes. It is caused by a mutation in the FGD1 gene located on the X chromosome, following an X-linked recessive inheritance pattern. Male children of carrier mothers have a 50% chance of inheriting the syndrome, while female carriers may exhibit mild symptoms but are less frequently affected. The syndrome manifests through short stature, specific facial features, and potential abnormalities of the hands and feet. Other symptoms may include undescended testicles, cleft lip or palate, and mild intellectual disabilities in some individuals.
Diagnosis typically involves a careful assessment of physical characteristics and may be confirmed through genetic testing or X-rays. While there is no cure for Aarskog syndrome, treatment focuses on supportive measures and surgical interventions to address associated conditions. Genetic counseling is advised for families with a history of the disorder, as there is currently no known prevention. Understanding Aarskog syndrome is vital for affected families to navigate the challenges and support available.
Aarskog syndrome
ALSO KNOWN AS: Aarskog-Scott syndrome; faciodigitogenital dysplasia or syndrome; faciogenital dysplasia; shawl scrotum syndrome
DEFINITION Aarskog syndrome is an extremely rare genetic disorder. This syndrome causes changes in the size and shape of certain bones and cartilage in the body. The face, fingers, and toes are most often affected.
Risk Factors
Aarskog syndrome mainly affects males. Those at risk of inheriting Aarskog syndrome are male children of mothers who do not have the disorder but who carry the gene for it.
Etiology and Genetics
Aarskog syndrome results from a mutation in the FGD1 gene, which is located on the short arm of the X chromosome at position p11.21. The inheritance pattern of this disease is typical of all sex-linked recessive mutations (those found on the X chromosome). Mothers who carry the mutated gene on one of their two X chromosomes have a 50 percent chance of transmitting this disorder to each of their male children. Female children of female carriers have a 50 percent chance of inheriting the gene and becoming carriers like their mothers. Although females rarely express the syndrome fully, female carriers may occasionally show minor manifestations. Affected males will pass the mutation on to all of their daughters but none of their sons.
The FGD1 gene specifies a guanine exchange factor, which is one of a class of proteins that act via an intracellular signaling network to turn on other genes at appropriate times during embryonic and fetal development. The specific genes and pathways known to be activated by the FGD1 protein are involved with the cell growth and differentiation of cells destined to become components of skin, bone, and cartilage. The mouse has proven to be a useful system for the study of this disorder, and the mouse data suggest that FGD1 signaling specifically affects the development of several different skeletal cell types, including chondrocytes, osteoblasts, and mesenchymal prechondrocytes.
Symptoms
The main symptoms of Aarskog syndrome are disproportionately short stature, abnormalities of the head and face (including a rounded face, wide-set eyes, slightly slanted eyes, drooping eyelids, a small nose, front-facing nostrils, an underdeveloped midportion of the face, a wide groove above the upper lip, a crease below the lower lip, folding of the top portion of the ear, or delayed teeth growth), and in some cases cleft lip or palate. Other symptoms may include a malformed scrotum; undescended testicles; small, wide hands and feet; short fingers and toes; mild webbing of fingers and toes or a simian crease in the palm of the hand; abnormalities of the sternum (mildly sunken chest); a protruding navel; inguinal hernias; ligament problems, resulting in hyperextension of the knees; or mild intellectual disabilities (in about one-third of those affected).
Screening and Diagnosis
The doctor will ask about symptoms and medical history and will perform a physical exam. The diagnosis of Aarskog syndrome is usually based on facial characteristics. The diagnosis can be confirmed by X-rays of the face and skull. Because this syndrome is caused by mutations in the FGD1 gene, genetic testing may also be used for diagnosis.
Treatment and Therapy
There is no known cure for Aarskog syndrome. Treatment is limited to supportive treatment and surgical procedures to treat conditions caused by the disorder, such as inguinal hernia, cleft lip or palate, or undescended testicles. In some cases, orthodontic treatment may help certain facial and dental abnormalities caused by the disorder. Supportive treatment generally includes educational assistance for those afflicted with intellectual disabilities, including advice and supportive treatment for parents.
Prevention and Outcomes
There is no known way to prevent Aarskog syndrome. Those with a family history of the disorder may be referred to a genetic counselor when deciding whether to have children.
Bibliography
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