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Menkes Disease

Kinky-Hair syndrome

Clinical Features

Menkes-Syndrom is a multisystem disorder of copper metabolism. The disease begins with an early effect on the central nervous system. The copper and ceruloplasmin concentration in blood are very low.

As Menkes disease is an X-linked recessive disease, the majority of patients are males. The often prematurely born boys develop normal within the first 6-12 weeks, but then show frequent vomiting, feeding difficulties and poor weight gain. There may be neonatal hypothermia and hyperbilirubinemia. Additional clinical features are apathy, hypotonia, and generalized seizures refractory to treatment.

The most striking diagnostic feature is the hair. It is short, sparse, brittle and breaks especially at places of contact. Under the microscope the hair shafts are twisted (pili torti). Patients with Menkes disease have a reduced life span.

Facial features:

• Pasty skin
• Thick cheeks
• Depressed nasal bridge
• Epicanthal folds

Skeletal findings:

• Metaphyseal flaring
• Osteoporosis

Additional features:

• Cutis laxa
• EEG abnormalities
• Microcephaly
• Tortuositas vasorum of retinal vessels
• Subdural haematomas
• Recurrent urinary tract infections
• Umbilical hernias

OHS (Occipital Horn Syndrome)

OHS is the mildest recognized form of Menkes-disease. The very characteristic feature are occipital horns, which are exostoses protruding from the occipital bone. The patients have osteoporosis and hypermobile joints. The clinical findings comprise recurrent urinary tract infections (bladder and ureter diverticulae), chronic diarrhea and orthostatic syncope. The intellectual capacity is described as low to borderline normal. The diagnosis is made around 5-10 years of age.

ATP7A related distal motor neuropathy

The age of onset is typically the second and third decade. Clinical findings include atrophy and weakness of distal muscels of hands and feet. Sometimes there is a proximal weakness in the legs. The ankle reflex might be absent. The sensory examination show a mild loss in fingers and toes.

Serum concentration of copper and ceruloplasmin

Genetic Information

The Menkes disease, the OHS and the ATP7A related Neuropathy follow a X-chromosomal pattern of inheritance and show mutations or deletions in ATP7A gene. The gene encodes for a ATPase which is responsible for the copper transport in membranes. The ATP7A gene has 23 exons and  is localized on the long arm of the X-chromosome (Xq13). Around 80% of patients have a mutation while in 15% deletions/duplications are observed.

Diagnostic