Hand-foot-genital syndrome

A rare genetic disorder affecting limb and urogenital development

Hand-foot-genital syndrome (HFGS) is a rare autosomal dominant genetic disorder characterized by limb malformations and urogenital anomalies. It is caused by mutations in the HOXA13 gene, which plays a crucial role in the development of the limbs and the urogenital tract.

Clinical Features

Individuals with hand-foot-genital syndrome typically present with a combination of limb and urogenital abnormalities. The severity and specific manifestations can vary among affected individuals.

Limb Abnormalities

- Hand Malformations: Patients often exhibit brachydactyly, which is the shortening of the fingers and toes. The thumbs may be particularly affected, showing hypoplasia or underdevelopment. - Foot Malformations: Similar to the hands, the feet may also show brachydactyly. There may be additional anomalies such as clubfoot or other positional deformities.

Urogenital Anomalies

- Females: Affected females may have uterine didelphys, a condition where the uterus is duplicated, or other Müllerian duct anomalies. - Males: Affected males may present with hypospadias, where the opening of the urethra is on the underside of the penis rather than at the tip.

Genetics

Hand-foot-genital syndrome is caused by mutations in the HOXA13 gene, which is located on chromosome 7p15.2. This gene is part of the homeobox gene family, which is involved in regulating patterns of anatomical development (morphogenesis) in animals, fungi, and plants.

The condition is inherited in an autosomal dominant manner, meaning that a single copy of the altered gene in each cell is sufficient to cause the disorder. This also implies that an affected individual has a 50% chance of passing the mutation to their offspring.

Diagnosis

Diagnosis of hand-foot-genital syndrome is primarily based on clinical evaluation and the identification of characteristic physical features. Genetic testing can confirm the diagnosis by identifying mutations in the HOXA13 gene.

Management

Management of hand-foot-genital syndrome is symptomatic and supportive. It may involve: - Orthopedic Interventions: Surgical correction of limb deformities may be necessary to improve function and mobility. - Urological and Gynecological Care: Management of urogenital anomalies may require surgical intervention and ongoing medical care. - Genetic Counseling: Families may benefit from genetic counseling to understand the inheritance pattern and implications for family planning.

Prognosis

The prognosis for individuals with hand-foot-genital syndrome varies depending on the severity of the symptoms and the presence of any associated complications. With appropriate management, many individuals can lead relatively normal lives.

Related Pages

• Brachydactyly
• Hypospadias
• Uterine didelphys
• Homeobox