Woodhouse–Sakati Syndrome

Overview

Woodhouse–Sakati syndrome (WSS) is a rare autosomal recessive multisystem genetic disorder characterized by a combination of endocrine, neurological, dermatological, and reproductive abnormalities. First described in 1983 by Woodhouse and Sakati, this syndrome most commonly presents with hypogonadism, diabetes mellitus, alopecia (hair loss), intellectual disability, and movement disorders such as dystonia or parkinsonism.

WSS is more prevalent in populations with a high rate of consanguineous marriages, particularly in the Middle East. It is a lifelong condition, and the severity and combination of symptoms can vary greatly between individuals. Early diagnosis and multidisciplinary care are crucial to improving quality of life and managing complications.

Causes

Woodhouse–Sakati syndrome is caused by mutations in the DCAF17 gene (formerly known as C2orf37), located on chromosome 2q31.1. This gene encodes a nuclear protein involved in various cellular functions, although its exact role remains unclear. The loss-of-function mutations in DCAF17 disrupt multiple cellular processes, particularly in tissues such as the endocrine glands, brain, and skin.

Inheritance Pattern:

• Autosomal recessive: An individual must inherit two copies of the mutated gene (one from each parent) to develop the condition.

• Carrier parents: Do not show symptoms but can pass the gene mutation to their children.

Symptoms

The clinical presentation of Woodhouse–Sakati syndrome varies, but common features affect the endocrine system, nervous system, hair and skin, reproductive function, and cognition.

Endocrine Features

• Hypogonadism: Failure of sexual development or infertility due to underactive gonads; more apparent during adolescence

• Diabetes mellitus: Usually type 2-like and often develops in adolescence or early adulthood

• Hypothyroidism: Underactive thyroid gland in some cases

Neurological Features

• Intellectual disability: Ranging from mild to moderate

• Dystonia: Involuntary muscle contractions leading to abnormal postures

• Parkinsonism: Including tremors, rigidity, and bradykinesia

• Hearing loss: Sensorineural in nature and often bilateral

• Seizures: Occur in some individuals

Dermatological Features

• Alopecia: Scalp hair thinning or complete hair loss, often starting in childhood or adolescence

• Loss of eyebrows and eyelashes

• Dry or scaly skin: In some cases

Other Features

• Facial dysmorphism: Mildly dysmorphic features such as prominent ears or long face

• Delayed growth and short stature: Often present in childhood

• Infertility: Especially in males due to testicular atrophy

Diagnosis

Diagnosis of Woodhouse–Sakati syndrome is based on clinical features, family history, and confirmed through genetic testing. Due to its multisystem involvement and overlap with other syndromes, a high index of suspicion is required for early diagnosis.

Diagnostic Steps:

• Clinical evaluation: Includes physical examination, neurological assessment, and review of endocrine function

• Laboratory tests:

  • Blood glucose levels (for diabetes)

  • Hormone panels (testosterone, estrogen, thyroid hormones)

• Brain MRI: May show abnormalities such as iron deposition in the basal ganglia

• Hearing tests: To assess the degree of sensorineural hearing loss

• Genetic testing: Confirms diagnosis by identifying mutations in the DCAF17 gene

Family screening:

• Carrier testing and genetic counseling: Recommended for family members in affected populations

Treatment

There is no cure for Woodhouse–Sakati syndrome. Management is supportive and tailored to each patient’s symptoms. A multidisciplinary team including endocrinologists, neurologists, dermatologists, audiologists, and geneticists is typically involved.

Endocrine Management

• Insulin or oral hypoglycemics: For diabetes management

• Hormone replacement therapy: For hypogonadism and hypothyroidism as indicated

• Dietary counseling: To manage metabolic complications

Neurological and Cognitive Support

• Anticholinergic or dopaminergic medications: May help manage dystonia and parkinsonian symptoms

• Antiepileptic drugs: If seizures are present

• Physical and occupational therapy: To improve mobility and daily functioning

• Special education services: For cognitive support

Other Supportive Therapies

• Hearing aids or cochlear implants: For sensorineural hearing loss

• Dermatological treatments: For alopecia and skin care

• Psychological support: For coping with chronic illness and developmental delays

Prognosis

The prognosis for Woodhouse–Sakati syndrome varies depending on the severity of symptoms and the organs involved. While the condition is chronic and progressive, life expectancy may extend into adulthood with appropriate medical care and symptom management.

Prognostic Factors:

• Early diagnosis and management: Improves long-term outcomes

• Diabetes control: Key to preventing long-term complications

• Severity of neurological involvement: Influences quality of life and independence

• Access to multidisciplinary care: Enhances symptom management and developmental progress

With comprehensive and consistent medical support, individuals with WSS can experience improved quality of life and functional abilities, though long-term challenges remain due to the progressive nature of the syndrome.