Woodhouse-Sakati Syndrome (WSS)

GENE: C2orf37;
INHERITANCE: Autosomal recessive;
ONSET: Adulthood;
SYMPTOMS: Hypogonadism, diabetes, alopecia, and neurological symptoms;
NOTES: WSS combines endocrine and neurological symptoms including high brain iron.

Overview

Woodhouse-Sakati Syndrome (WSS) is a rare genetic disorder that affects multiple body systems, including endocrine, neurological, and dermatological functions. It is marked by a combination of hormonal deficiencies, movement disorders, and progressive neurological decline. Symptoms often appear in childhood or adolescence and progress over time.

Genetics

WSS is caused by mutations in the C2orf37 gene and is inherited in an autosomal recessive manner. This means a child must inherit two copies of the mutated gene (one from each parent) to develop the condition. Carriers with only one copy are typically unaffected.

Symptoms

Clinical features of WSS vary but often include:

Hypogonadism: delayed or absent puberty due to hormonal deficiencies
Diabetes mellitus: resulting from pancreatic involvement
Alopecia: progressive hair loss, including scalp, eyebrows, and eyelashes
Neurological symptoms: progressive dystonia, spasticity, and intellectual disability
Hearing loss: may develop in some affected individuals

Progression

WSS is progressive, with endocrine and neurological symptoms worsening over time. Early detection can help manage metabolic complications, while ongoing supportive care is important for movement and cognitive challenges.

Management

There is no cure for WSS. Treatment focuses on managing symptoms and may include:

Hormone replacement therapy for hypogonadism
Diabetes management through diet, medication, or insulin
Physical and occupational therapy to maintain mobility and function
Supportive care for hair loss, hearing, and neurological symptoms

Resources

1. NBIA Disorders.
2. Childhood Dementia.