SNP Shot: Genomic Insights

Woodhouse-Sakati syndrome is a rare condition affecting both the endocrine and nervous systems. Its impact varies considerably, even among family members.

A key feature of Woodhouse-Sakati syndrome is hypogonadism, where the body produces insufficient sex hormones. This typically becomes noticeable during adolescence. Without hormone replacement, individuals may not develop typical secondary sexual characteristics. Females may have streak gonads instead of functional ovaries and a small or absent uterus. Males may have testes that produce little or no sperm. This hormone deficiency often leads to infertility.

Certain facial features are often associated with the syndrome, including a long, triangular face, widely spaced eyes (hypertelorism), and a prominent nasal bridge. Hair loss (alopecia), beginning in childhood, is also common, affecting scalp hair, eyelashes, eyebrows, and facial hair in men. By their mid-twenties, most individuals develop diabetes mellitus and may also experience hypothyroidism.

Neurological problems are also frequently observed. Dystonias, movement disorders characterized by involuntary muscle contractions or twisting movements, often begin in adolescence or young adulthood. Other neurological symptoms may include speech difficulties (dysarthria), swallowing problems (dysphagia), and mild intellectual disability.

Sensorineural hearing loss, ranging from mild to total, can occur due to inner ear changes, typically starting in adolescence.

Some individuals with Woodhouse-Sakati syndrome show abnormal iron deposits in the brain on medical imaging. This has led to its classification as a neurodegeneration with brain iron accumulation (NBIA) disorder in some cases.

Researchers sometimes categorize Woodhouse-Sakati syndrome into two types. Type 1 is associated with more severe neurological problems, while type 2 is characterized by milder or absent neurological symptoms.

Inheritance:

Woodhouse-Sakati syndrome follows an autosomal recessive inheritance pattern. This means an individual must inherit two copies of the mutated gene, one from each parent, to develop the condition. The parents, who each carry one copy, are typically asymptomatic.