Woodhouse-Sakati syndrome

Woodhouse-Sakati syndrome is a disorder that primarily affects the body's network of hormone-producing glands (the endocrine system) and the nervous system. The signs and symptoms of this condition vary widely among affected individuals, even within the same family.

People with Woodhouse-Sakati syndrome produce abnormally low amounts of hormones that direct sexual development (hypogonadism), which typically becomes apparent during adolescence. Without hormone replacement therapy, affected individuals do not develop secondary sexual characteristics such as pubic hair, breast growth in women, or a deepening voice in men. Women with Woodhouse-Sakati syndrome do not have functional ovaries and may instead have undeveloped tissues called streak gonads. The uterus may also be small or absent. Men with this disorder have testes that produce little to no sperm. As a result, people with Woodhouse-Sakati syndrome have difficulty having biological children (a condition called infertility).

Some affected individuals have certain characteristic facial features, including a long, triangular face; widely spaced eyes (hypertelorism); and a prominent bridge of the nose. People with Woodhouse-Sakati syndrome also experience hair loss (alopecia) that begins in childhood and worsens over time. Eyelashes and eyebrows are sparse or absent, and affected men have little or no facial hair. By their mid-twenties, almost all affected individuals develop diabetes mellitus, and they may also have reduced production of thyroid hormones (hypothyroidism). 

Individuals with Woodhouse-Sakati syndrome may have neurological problems. A group of movement abnormalities called dystonias are common in affected individuals, and they generally begin in adolescence or young adulthood. These movement abnormalities can include involuntary tensing of the muscles (muscle contractions) or twisting of specific body parts such as an arm or a leg. Other neurological features can include difficulty with speech (dysarthria) or swallowing (dysphagia), and mild intellectual disabilities. 

Changes in the inner ears can lead to hearing loss (sensorineural hearing loss) in people with Woodhouse-Sakati syndrome. The hearing loss can range from mild to total. This loss usually occurs in adolescence.

In some affected individuals, abnormal deposits of iron in the brain have been detected with medical imaging. For this reason, Woodhouse-Sakati syndrome is sometimes classified as part of a group of disorders called neurodegeneration with brain iron accumulation (NBIA).

Some researchers classify Woodhouse-Sakati syndrome into two types, depending on the signs and symptoms. People with Woodhouse-Sakati syndrome type 1 tend to have more severe neurological problems, and those with type 2 have milder or no neurological problems.