Menkes syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Menkes syndrome is a disorder that affects copper levels in the body. It is characterized by sparse, kinky hair; an inability to gain weight and grow at the expected rate (faltering weight); and deterioration of the nervous system. Additional signs and symptoms include weak muscle tone (hypotonia), sagging facial features, seizures, developmental delay, and intellectual disability. Children with Menkes syndrome typically begin to develop symptoms during infancy and often do not live past age 3. Early treatment with copper may improve the prognosis in some affected individuals. In rare cases, symptoms begin later in childhood.

Occipital horn syndrome (sometimes called X-linked cutis laxa) is a less severe form of Menkes syndrome that begins in early to middle childhood. It is characterized by wedge-shaped calcium deposits in a bone at the base of the skull (the occipital bone), coarse hair, and loose skin and joints.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Mutations in the ATP7A gene cause Menkes syndrome. The ATP7A gene provides instructions for making a protein that is important for regulating copper levels in the body. Copper is necessary for many cellular functions, but it is toxic when present in excessive amounts. Mutations in the ATP7A gene result in poor distribution of copper to the body's cells. Copper accumulates in some tissues, such as the small intestine and kidneys, while the brain and other tissues have unusually low levels of copper. The decreased supply of copper can reduce the activity of numerous copper-containing enzymes that are necessary for the structure and function of bone, skin, hair, blood vessels, and the nervous system. The signs and symptoms of Menkes syndrome and occipital horn syndrome are caused by the reduced activity of these copper-containing enzymes.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Menkes syndrome is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

In about one-third of cases, Menkes syndrome is caused by new mutations in the ATP7A gene. People with a new mutation do not have a history of the disorder in their family.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

The incidence of Menkes syndrome and occipital horn syndrome is estimated to be 1 in 100,000 newborns.

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 palate morphology · Very frequent (99-80%)

Any abnormality of the palate, i.e., of roof of the mouth.

Aplasia/Hypoplasia of the abdominal wall musculature · Very frequent (99-80%)

Absence or underdevelopment of the abdominal musculature.

Developmental regression · Very frequent (99-80%)

Loss of developmental skills, as manifested by loss of developmental milestones.

Dilatation · Very frequent (99-80%)

An abnormal increase in the diameter of an artery or vein, either as a diffuse dilatation or as a localized, sac-like outpouching of the vessel wall (aneurysm).

Dry skin · Very frequent (99-80%)

Skin characterized by the lack of natural or normal moisture.

Fatigue · Very frequent (99-80%)

A subjective feeling of tiredness characterized by a lack of energy and motivation.

Feeding difficulties in infancy · Very frequent (99-80%)

Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.

Hyperextensible skin · Very frequent (99-80%)

A condition in which the skin can be stretched beyond normal, and then returns to its initial position.

Hypertonia · Very frequent (99-80%)

A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.

Hypotonia · Very frequent (99-80%)

Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.

Inguinal hernia · Very frequent (99-80%)

Protrusion of the contents of the abdominal cavity through the inguinal canal.

Intracranial hemorrhage · Very frequent (99-80%)

Hemorrhage occurring within the skull.

Joint hypermobility · Very frequent (99-80%)

The capability that a joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes.

Microcephaly · Very frequent (99-80%)

Head circumference below 2 standard deviations below the mean for age and gender.

Other findings in the same source

From: Orphanet

Additional reported features include Pectus excavatum (Very frequent (99-80%)); Seizure (Very frequent (99-80%)); Sparse hair (Very frequent (99-80%)); Spasticity (Very frequent (99-80%)); Umbilical hernia (Very frequent (99-80%)); Woolly hair (Very frequent (99-80%)); Hernia (Very frequent (99-80%)); Hypopigmentation of hair (Very frequent (99-80%)); Abnormal metaphysis morphology (Frequent (79-30%)); Abnormality of the carotid arteries (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Menkes syndrome is Metabolic Medicine, with a metabolic specialist / clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with metabolic specialist / clinical geneticist referral.

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.

• Is a biochemical or molecular result needed to clarify the diagnosis?
• Does this condition require an individual plan for illness or reduced food intake?
• Should nutrition advice come from a specialist metabolic dietitian?

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.