Woodhouse-Sakati syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

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.

ORPHANET DEFINITION Woodhouse-Sakati syndrome is a multisystemic disorder characterized by hypogonadism, alopecia, diabetes mellitus, intellectual deficit and extrapyramidal signs with choreoathetoid movements and dystonia.

Inheritance

From: MedlinePlus Genetics, National Library of Medicine

Autosomal recessive

Frequency in the source

From: MedlinePlus Genetics, National Library of Medicine

Reported family(ies): 25.0; Worldwide. This is a published case count, not prevalence. Point prevalence: <1 / 1 000 000; Worldwide; Class only.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal T-wave · Very frequent (99-80%)

An abnormality of the T wave on the electrocardiogram, which mainly represents the repolarization of the ventricles.

Abnormal spermatogenesis · Very frequent (99-80%)

Incomplete maturation or aberrant formation of the male gametes.

Alopecia · Very frequent (99-80%)

A noncongenital process of hair loss, which may progress to partial or complete baldness.

Aplasia/Hypoplasia of the eyebrow · Very frequent (99-80%)

Absence or underdevelopment of the eyebrow.

Bilateral sensorineural hearing impairment · Very frequent (99-80%)

A form of sensorineural hearing impairment that affects both ears.

Choreoathetosis · Very frequent (99-80%)

Involuntary movements characterized by both athetosis (inability to sustain muscles in a fixed position) and chorea (widespread jerky arrhythmic movements).

Decreased response to growth hormone stimulation test · Very frequent (99-80%)

Insufficient responses to growth hormone (GH) provocation tests. GH deficiency is defined as a serum peak GH concentration less than 10 ng/mL on provocation with a combination of at least two separate stimulation tests.

Decreased serum estradiol · Very frequent (99-80%)

A reduction below normal concentration of estradiol in the circulation.

Decreased testicular size · Very frequent (99-80%)

Reduced volume of the testicle (the male gonad).

Delayed puberty · Very frequent (99-80%)

Passing the age when puberty normally occurs with no physical or hormonal signs of the onset of puberty.

Delayed skeletal maturation · Very frequent (99-80%)

A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.

Dysarthria · Very frequent (99-80%)

Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.

Dystonia · Very frequent (99-80%)

An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.

Growth delay · Very frequent (99-80%)

A deficiency or slowing down of growth pre- and postnatally.

Other findings in the same source

From: Orphanet

Additional reported features include Hyperinsulinemia (Very frequent (99-80%)); Hyperlipidemia (Very frequent (99-80%)); Hypogonadism (Very frequent (99-80%)); Hypoplasia of the fallopian tube (Very frequent (99-80%)); Hypoplasia of the uterus (Very frequent (99-80%)); Hypothyroidism (Very frequent (99-80%)); Insulin-resistant diabetes mellitus (Very frequent (99-80%)); Intellectual disability, mild (Very frequent (99-80%)); Mental deterioration (Very frequent (99-80%)); Micropenis (Very frequent (99-80%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: MedlinePlus Genetics, National Library of Medicine

Adolescent; Childhood

Inheritance in the source

From: MedlinePlus Genetics, National Library of Medicine

Autosomal recessive

Frequency and the population described

From: MedlinePlus Genetics, National Library of Medicine

Reported family(ies): 25.0; Worldwide. This is a published case count, not prevalence. Point prevalence: <1 / 1 000 000; Worldwide; Class only.

Understanding the inheritance label

From: MedlinePlus Genetics

An autosomal recessive pattern usually involves disease-causing changes in both copies of a gene. Parents may each carry one altered copy without having the condition themselves. A genetic counsellor can explain carrier testing and reproductive implications using the actual laboratory findings, rather than the condition name alone.

Which doctor should you see?

The suggested department for discussing Woodhouse-Sakati syndrome is Endocrinology, with a endocrinologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which hormone or metabolic finding is important in this case?
• How should test timing and current medicines be taken into account?
• What follow-up would show whether the care plan is working?

Treatment discussions and follow-up

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.