Hand-foot-genital syndrome

Overview

Hand-foot-genital syndrome (HFGS) is a rare genetic disorder that affects the development of the limbs and the genitourinary system. Individuals with HFGS typically present with malformations of the hands and feet, such as shortened thumbs or small feet, along with abnormalities of the urinary and reproductive organs. The condition is congenital and varies in severity from person to person. HFGS was first described in the medical literature in the 1970s and is classified as a limb malformation syndrome.

Causes

Hand-foot-genital syndrome is caused by mutations in the HOXA13 gene, which plays a crucial role in the development of limbs and the urogenital tract during embryogenesis. The syndrome follows an autosomal dominant inheritance pattern, meaning that a single copy of the mutated gene from one parent is sufficient to cause the disorder. In some cases, the mutation occurs de novo (newly) in the affected individual with no family history.

Symptoms

The clinical features of HFGS involve both skeletal and genitourinary systems. Common symptoms include:

• Hand abnormalities: Short thumbs (brachydactyly), broad thumbs, or duplication of thumb bones.

• Foot abnormalities: Small feet, shortened great toes, and abnormalities in the metatarsal bones.

• Genitourinary anomalies in females: Abnormal development of the uterus and vagina, such as uterine didelphys (double uterus), septate uterus, or vaginal septum, which may lead to reproductive difficulties.

• Genitourinary anomalies in males: Hypospadias (urethra opens on the underside of the penis), undescended testes, or small penis.

• Urinary tract issues: Vesicoureteral reflux (backflow of urine from the bladder into the ureters), which may increase the risk of urinary tract infections.

Diagnosis

Diagnosis of hand-foot-genital syndrome is based on clinical evaluation and confirmed by genetic testing. Diagnostic steps may include:

• Physical examination: Identifying characteristic limb abnormalities and genitourinary malformations.

• Imaging studies: X-rays of hands and feet to assess bone structure; pelvic ultrasound or MRI to evaluate reproductive organs.

• Genetic testing: Molecular analysis to detect mutations in the HOXA13 gene confirms the diagnosis.

• Family history: Evaluation for other affected individuals within the family, especially in autosomal dominant inheritance.

Treatment

There is no cure for HFGS, and treatment focuses on managing symptoms and correcting structural abnormalities. A multidisciplinary approach is often necessary, including:

• Orthopedic care: Surgical or non-surgical management of limb deformities to improve function and appearance.

• Urological treatment: Management of urinary tract infections, reflux, or obstruction; may involve surgery or catheterization.

• Gynecological care: Surgical correction of uterine or vaginal anomalies to improve fertility and menstrual function.

• Genetic counseling: Recommended for affected individuals and their families to understand inheritance risks and options for prenatal diagnosis.

Prognosis

The prognosis for individuals with hand-foot-genital syndrome is generally favorable, especially with timely medical and surgical management. Most affected individuals have a normal lifespan and intelligence. However, reproductive and urinary complications may affect quality of life and require long-term care. Early diagnosis, proper monitoring, and coordinated care can significantly improve outcomes and reduce complications.