Menkes Disease Clinical Presentation

Updated: Oct 29, 2014
  • Author: Celia H Chang, MD; Chief Editor: Amy Kao, MD  more...
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Presentation

History

Children with the classic form of Menkes disease usually present at 2-3 months of age with the following:

  • Loss of developmental milestones

  • Profound truncal hypotonia

  • Epilepsy, divided into 3 periods by Bahi-Buisson et al [8] : Early stage, median age 3 months, with focal clonic status; intermediate stage, median age 10 months, with intractable infantile spasms; late state, median age 25 months, with multifocal seizures, tonic spasms, and myoclonus [9]

  • Failure to thrive

People with milder variants may have minimal neurological symptoms with normal intelligence or only mild mental retardation and autonomic dysfunction.

One third of the patients with Menkes disease in Japan from 1992-2002 were born before 37 weeks or weighed less than 2500 g. Seventeen percent of patients were born both before 37 weeks and weighing less than 2500 g.

Next:

Physical Examination

Findings include abnormal kinky hair, eyebrows, and eyelashes (see the image below) as follows:

Four-month-old patient with classic Menkes disease Four-month-old patient with classic Menkes disease. His hair is depigmented and lusterless with pili torti and the skin is pale with eczema.

See the list below:

  • Short, sparse, coarse, twisted

  • Shorter and sparser on the sides and back

  • Often lightly or abnormally pigmented; can be white, silver, or gray (In ethnic groups with black hair, the hair can also be blonde or brown.)

Abnormal facies include the following:

  • Jowly with sagging cheeks and ears

  • Depressed nasal bridge

  • High arched palate

  • Delayed tooth eruption

Progressive cerebral degeneration includes the following:

  • Loss of developmental milestones

  • Seizures

  • Profound truncal hypotonia with appendicular hypertonia

  • Temperature instability

Ocular manifestations include the following:

  • Ptosis

  • Visual inattention

  • Optic disc pallor with decreased pupillary responses to light

  • Iris hypoplasia and hypopigmentation

Connective-tissue abnormalities include the following:

  • Loose skin at the nape of the neck and over the trunk

  • Joint hypermobility

  • Polypoid masses, which can be multiple, in the gastrointestinal tract

  • Umbilical and inguinal hernias, which can be bilateral

  • Bladder diverticula (see the following image)

    Diverticula of the bladder in a boy with Menkes di Diverticula of the bladder in a boy with Menkes disease.
  • Dilated ureters

  • Emphysema

Vascular defects include the following:

  • Arterial rupture

  • Brachial, lumbar, and iliac artery aneurysms

  • Internal jugular vein aneurysms

  • Thrombosis

  • Pulmonary artery hypoplasia

Skeletal changes include the following:

  • Multiple congenital fractures, deformities (see the following image)

    The clavicles are short with hammer-shaped distal The clavicles are short with hammer-shaped distal ends in a patient with Menkes disease.
  • Osteoporosis

  • Metaphyseal spurring and widening (see the following image)

    Flared metaphyses of the ulna and radius in a 5-mo Flared metaphyses of the ulna and radius in a 5-month-old patient with classic Menkes disease.
  • Diaphyseal periosteal reaction

  • Scalloping of the posterior portion of the vertebral bodies

  • Pectus excavatum

  • Wormian bones

Bleeding diathesis and renal calculi are also noted.

Patients with occipital horn syndrome are affected predominantly by connective-tissue and bony changes, including hyperelastic and bruisable skin, hyperextensible joints, hernias, bladder diverticula, and multiple skeletal abnormalities, including occipital exostoses ("horns"), which are wedge-shaped calcifications within the occipital tendinous insertion of the trapezius and sternocleidomastoid muscles (see the following images).

Lax skin in a patient with occipital horn syndrome Lax skin in a patient with occipital horn syndrome.
Occipital horns (arrow) in a 14-year-old boy with Occipital horns (arrow) in a 14-year-old boy with occipital horn syndrome.

The horns may not be present in early childhood. These patients also may have mild mental retardation and autonomic dysfunction. Serum copper and ceruloplasmin levels are low but not to the same degree as in Menkes disease. Copper also accumulates in cultured fibroblasts but to a lesser degree than in Menkes disease. Occipital horns can also be present in patients with the classic form of Menkes disease and have been noted in patients as young as 2 years of age.

Other clinical variants referred to as mild Menkes disease are characterized by ataxia and mild mental retardation.

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