Neurological complications of infantile osteopetrosis

Abstract

Seven cases of infantile osteopetrosis are presented. Five of these were available for detailed clinical examination and 2 for retrospective review, including autopsy slides. Neurological deficits in these patients are reviewed. Involvement of the central nervous system parenchyma was suggested by observations of delayed development, ocular abnormalities, and reflex changes as well as radiographic and autopsy findings. Cerebral atrophy was present in several of our patients as well as some reported in the literature and may account for the ventricular enlargement found in many of these patients. Though hydrocephalus may be present, it is unclear that this is frequent or that it can occur without antecedent intracranial hemorrhage. The large head size is not accounted for by calvarial thickening or by hydrocephalus. Despite our patients' small stature, pituitary function appeared to be normal. Surgical decompression may stabilize cranial nerve function, particularly when the optic nerves are involved.

Major cerebral arterial and venous disease in osteopetrosis.

“…In the infantile, autosomal recessive type, hydrocephalus and developmental delay may be seen. 7 " In both forms of the disease, cranial nerve palsies are common. Compression of cranial nerves 1-8 has been reported, but not nerves 9-12.…”

“…18 Features suggestive of intra-axial involvement, of uncertain significance, include vertical nystagmus, 7 neuroaxonal dystrophy, 7 " EEG abnormalities, 7 -^ 2I neuronal storage disease, 22 and signs of pyramidal dysfunction not explained by stenosis of the foramen magnum or spinal canal. 7 Blindness, with optic atrophy and pendular nystagmus, is frequently seen but poorly understood. Narrowing of the optic foramina has frequently been observed 9 23~27 and surgical unroofing of the optic canal has been advocated.…”

Long-term follow-up of two children with a variant of mild autosomal recessive osteopetrosis undergoing bone marrow transplantation

“…17 Most of these result from direct compression of cranial nerves and are most pronounced in patients with early disease onset. 20 Both of our patients only showed severe visual impairment with bilateral optic nerve subatrophy, which stabilized after BMT. 21 Hypercalcemia requiring treatment with saline diuresis, diuretics, bisphosphonates, synthetic calcitriol or dyalison is an unusual complication that occurs in about 35% of patients 18 with osteopetrosis undergoing BMT.…”

Primary Optic Atrophy in Osteopetrosis

“…7 Neurologic problems, such as hydrocephalus, facial paresis, seizures, and mental retardation, are also common. 5,8 Dental problems are also common. Rickets is a paradoxical complication in osteopetrotic bones due to inability of osteoclasts to maintain calcium and phosphate balance in extracellular fluid.The most severely affected patients die during infancy as a result of bone marrow failure and infections 9 less severely affected individuals rarely survive beyond the 2 nd decade.…”