Hand-foot-genital syndrome

Hand-foot-genital syndrome (HFGS) is a rare inherited condition characterized by limb malformations and urogenital anomalies. It is caused by mutations in the HOXA13 gene located on chromosome 7p15.2, which plays a critical role in the development of the distal limbs and the genitourinary tract during embryonic development. The condition is also sometimes referred to as hand-foot-uterus syndrome due to the prominent uterine anomalies seen in affected females. The limb abnormalities typically involve the hands and feet and include short first metacarpals, small and pointed distal phalanges of the thumbs (short thumbs), clinodactyly of the fifth finger, short great toes, and abnormal positioning or shortening of other bones in the feet. In females, genital anomalies commonly include a bicornuate uterus or uterus didelphys (duplicated or partially divided uterus), which can lead to complications such as recurrent miscarriages, preterm labor, and infertility. Males may present with hypospadias (abnormal urethral opening) and chordee. Both sexes may experience urinary tract anomalies, including ectopic ureteral openings, vesicoureteral reflux, and recurrent urinary tract infections. There is no cure for hand-foot-genital syndrome. Management is supportive and symptom-directed. Surgical correction may be considered for significant hypospadias in males or for urinary tract anomalies. Reproductive counseling and obstetric monitoring are important for affected females, and surgical intervention for uterine malformations (such as metroplasty) may be considered in cases of recurrent pregnancy loss. Genetic counseling is recommended for affected individuals and their families given the autosomal dominant inheritance pattern.

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