Hand-foot-genital syndrome is an inherited, congenital condition characterized by differences in the limbs and abnormalities of the urogenital system. The signs are present from birth and stem from changes during embryonic development. This is a rare disorder, with a limited number of cases documented in medical literature.
The Genetic Roots of Hand-Foot-Genital Syndrome
The cause of hand-foot-genital syndrome is a mutation in the HOXA13 gene. This gene provides instructions for making a protein that is active during early development in the womb. The HOXA13 protein has a function in regulating the formation of the limbs, the urinary tract, and the reproductive system.
This condition is inherited in an autosomal dominant pattern. This means that inheriting just one copy of the mutated HOXA13 gene from a single parent is enough to cause the syndrome. An individual with the condition has a 50% chance of passing the altered gene to each of their children. In some instances, the genetic mutation can occur spontaneously in an individual without a family history of the disorder.
Recognizable Limb Differences
A characteristic of the syndrome is the bilateral shortening of the thumbs and great toes. This is due to an underdeveloped final bone (distal phalanx) in these digits, which can affect dexterity and the ability to pinch or grasp with the thumb.
Other limb-related signs include short feet and an inward curve to the fifth finger, known as clinodactyly. In some individuals, the bones of the wrist and ankle may show delayed maturation. The great toe might also display a deviation toward the inside of the foot. These limb differences do not require surgical intervention.
Impact on the Urogenital System
The effects on the urogenital system vary among individuals and differ between sexes. In males, this can include hypospadias, a condition where the opening of the urethra is on the underside of the penis rather than at the tip. Abnormalities affecting the ureters, the tubes that carry urine from the kidneys to the bladder, can also occur.
In females, the syndrome can involve incomplete Müllerian fusion. The Müllerian ducts are embryonic structures that develop into the uterus, cervix, and upper part of the vagina. Incomplete fusion can result in a divided uterus (bicornuate or septate) and occasionally a duplicated cervix or vagina. These structural differences can lead to complications such as recurrent urinary tract infections or the backward flow of urine from the bladder to the kidneys.
How Hand-Foot-Genital Syndrome is Diagnosed
Diagnosing hand-foot-genital syndrome begins with a physical examination to identify the characteristic features of the limbs and genitalia. A doctor will assess the structure of the hands and feet and may inquire about urinary symptoms. The evaluation is supported by imaging studies.
X-rays of the hands and feet are used to confirm bone abnormalities. To assess the urogenital system, doctors employ imaging techniques like ultrasound or MRIs to examine the kidneys, bladder, and reproductive organs for structural variations. While clinical and imaging findings are suggestive, a definitive diagnosis is established through molecular genetic testing that identifies a pathogenic variant in the HOXA13 gene.
Managing the Condition and Outlook
Management focuses on addressing specific symptoms and preventing complications, particularly those of the urogenital tract. Surgical intervention may be necessary to correct structural issues. Procedures can include ureteric reimplantation to fix the ureter-bladder connection or surgical repair of hypospadias in males.
For females, surgery to remove a uterine septum or unify a bicornuate uterus is generally considered only in cases of recurrent pregnancy loss. Ongoing medical care may involve prophylactic antibiotics to prevent recurrent urinary tract infections. Because the condition is genetic, counseling is recommended for affected individuals and their families to discuss inheritance and family planning. Individuals with this syndrome typically have a normal lifespan and intelligence, and fertility is often unaffected.