7p15 deletion as the cause of hand-foot-genital syndrome.
Hand-foot-genital syndrome (HFGS) is a rare genetic disorder that is characterized by malformations in the hands, feet and the genitourinary tract. The most frequent limb abnormalities in HFGS include short thumbs and fingers, small feet, clinodactyly (curvature) of the fifth finger, and hallux valgus (a deformity of the joint in the big toe that causes it to point outward towards the other toes). Genitourinary tract malformations can include hypospadias (in males, where the opening of the urethra is on the underside of the penis), cryptorchidism (in males, where one or both of the testicles fail to descend into the scrotum), or bicorne uterus (in females, where the uterus appears heart-shaped).
HFGS is caused by the loss of function of the HOXA13 gene, located in the 7p15 region of chromosome 7. This loss of function may be caused by mutation of HOXA13 gene or deletion of the segment, which includes this gene. HOX genes – such as HOXA13 – are primarily involved in developmental processes throughout life, and loss of them results in developmental issues. HOXA13 is responsible for the development of the limbs and genitourinary tract; therefore, loss of this gene results in improper development of these areas, resulting in the malformations above.
This article describes a patient with HFGS with a 12.7 Mb 7p15 deletion (specifically, within the region 7p14.3-7p15.3) which includes deletion of the HOXA13 gene. Above typical manifestations of HFGS this patient had neurodevelopmental delay, short stature, facial dysmorphism, and ear abnormalities. These additional features are most likely caused by deletion of other neighboring HOXA genes, involved in neurological development ( HOXA1 ) and proper height development (HOXA5, HOXA11 ), as well as some other genes in this area. Basically the larger the deletion, the worse the consequences.
The article concludes that patients with HFGS should test to see if their symptoms are caused by a microdeletion, or simply a HOXA13 mutation. That way, treatment options can be adjusted in case more genes are being affected than originally expected.
Yokoyama et al. “7p15 deletion as the cause of hand-foot-genital syndrome: a case report, literature review and proposal of a minimum region for this phenotype”. Molecular Cytogenetics 2017, v. 10:42.