McKusick-Kaufman syndrome

McKusick-Kaufman syndrome (MKKS), also known as hydrometrocolpos-polydactyly syndrome, is a rare autosomal recessive genetic disorder characterized by a triad of congenital anomalies: hydrometrocolpos (accumulation of fluid in the vagina and uterus in females), postaxial polydactyly (extra fingers or toes on the outer side of the hands or feet), and congenital heart defects. The condition is caused by mutations in the MKKS gene (also called BBS6), located on chromosome 20p12, which encodes a protein involved in protein processing and folding (a chaperonin-like protein). The syndrome primarily affects the reproductive, skeletal, and cardiovascular systems. In females, hydrometrocolpos is often the presenting feature at birth and can cause abdominal distension, urinary obstruction, and bowel compression. In males, genital anomalies may include hypospadias, prominent scrotal raphe, or cryptorchidism, though the phenotype is generally less distinctive. Congenital heart defects are variable and may include atrioventricular canal defects, atrial septal defects, or other structural cardiac malformations. Postaxial polydactyly may affect one or more limbs and can range from a small skin tag to a fully formed extra digit. McKusick-Kaufman syndrome was initially described in the Old Order Amish population, where it occurs with higher frequency due to a founder effect. It is important to distinguish MKKS from Bardet-Biedl syndrome (BBS), as mutations in the same MKKS/BBS6 gene can cause both conditions, and some features overlap. Children initially diagnosed with MKKS should be monitored for additional features of BBS, such as obesity, retinal dystrophy, renal anomalies, and learning difficulties, which may emerge later in childhood. Treatment is primarily surgical and supportive, including drainage or surgical correction of hydrometrocolpos, removal of extra digits, and repair of congenital heart defects as needed. With appropriate management, the prognosis is generally favorable.

Common questions about McKusick-Kaufman syndrome