In the classic form, the disease starts before
age 3 months by loss of neurologic development (hypotonia progressively
evolving to spasticity), severe seizures, and subdural hematoma. Patients
manifest hypopigmentation, growth failure, skeletal defects, arterial
aneurysms, and progressive cerebral and cerebellar degeneration. Myoclonic
seizures and hypothermia are frequent. Fragile steely depigmented (grayish
or ivory colored) hair is present in the newborn period; they appear as pili
torti at microscopic examination. Typical facies consist of frontal or
occipital bossing, abnormal or absent eyebrows, pudgy cheeks with sagging
jowls, micrognathia, and pallor. Characteristic radiographic changes include
wormian bones in lamboid and sagittal sutures, anterior rib flaring, spur
formation on the femoral and humeral metaphysis, and osteoporosis.
Arteriography shows elongation, tortuosity, narrowing, and dilatation of
cerebral, visceral, and limbs arteries. Gastroesophageal reflux and
recurrent aspiration frequently accompany progressive central nervous system deterioration.
Joint hyperlaxity and capillary fragility caused by defective lysyl oxidase,
a copper-containing enzyme involved in the cross-linking of collagen similar
to Ehlers-Danlos syndrome. Diverticular malformations of the bladder and
ureters. Treatments have been generally unsuccessful; oral copper helps
control the seizures but has no effect on progression of neurologic damage.
Death within 3 years as a consequence of intractable seizures or
pneumonia.