Dermatologic Manifestations of Menkes Kinky Hair Disease

Updated: Oct 27, 2016
  • Author: Suguru Imaeda, MD; Chief Editor: William D James, MD  more...
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Overview

Background

Menkes kinky hair syndrome is an X-linked recessive multisystemic lethal disorder of copper metabolism. The clinical phenotype is marked by fine silvery wiry hair, doughy skin, connective-tissue disturbances, and progressive neurologic deterioration. In 1962, Menkes et al [1] first described the syndrome, and, 10 years later, Danks et al [2, 3] noted the association with copper metabolism. The affected copper-transporting p-type ATPase (ATP7A) gene was cloned in 1993.

In Menkes kinky hair syndrome, intestinal copper uptake by brush border cells is normal, but copper transport to other tissues is affected. [4] This change alters the activities of various copper-dependent metalloenzymes. Male infants who are affected typically die by the time they are aged 2-3 years. Carrier female patients may have only a hair-shaft abnormality (ie, pili torti).

See the image below.

Classic menkes kinky hair disease in an 8-month-ol Classic menkes kinky hair disease in an 8-month-old male infant.
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Pathophysiology

In Menkes kinky hair syndrome, a defect in intestinal copper transport with associated low serum copper and ceruloplasmin levels results in a deficiency in copper-dependent enzyme activity. Copper-dependent metalloenzymes relevant to the clinical phenotype include tyrosinase (pigmentation of skin and hair), lysyl oxidase (elastin and collagen cross-linking), ascorbate oxidase (skeletal development), monoamine oxidase (possibly responsible for pili torti), superoxide dismutase (free-radical detoxification), dopamine beta-hydroxylase (catecholamine production), peptidyl-glycine alpha-amidating mono-oxygenase (bioactivation of peptide hormones), and cytochrome c oxidase (electron transport and possibly responsible for hypothermia). The resulting defects are reflected in the clinical phenotype.

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Epidemiology

Frequency

In Australia, Menkes kinky hair syndrome occurs in 1 case per 35,000 population. Worldwide, Menkes kinky hair syndrome occurs in 1 case per 300,000 population.

Race

No racial predilection exists for Menkes kinky hair syndrome.

Sex

The phenotype of Menkes kinky hair syndrome is manifest in male patients.

Female carriers may have pili torti and uneven skin pigmentation, which appears unilaterally or along the lines of Blaschko.

Age

Symptoms of Menkes kinky hair syndrome are noted within the patient's first few months of life. Typical initial signs are hypotonia, failure to thrive, and seizures.

Seizures usually begin within the patient's first few days or months of life. Hypotonia and developmental delays are typically noted during the patient's first year of life.

Hair changes are usually not present at birth but manifest soon thereafter. Not all hairs are affected. Scalp and eyebrow hairs are most commonly short; sparse; coarse; steel wool–like; and white, silver, or gray.

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Prognosis

The prognosis for Menkes kinky hair syndrome is poor. Progressive neurologic deterioration occurs in persons with Menkes kinky hair syndrome. Death, usually due to pneumonia, occurs by the time the patient is aged 2-3 years.

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Patient Education

Genetic counseling is indicated in Menkes kinky hair syndrome.

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