Recessive Opticocerebellobulbospinal Leukodystrophy
Objective: To describe a novel adolescent-onset recessive leukodystrophy with opticocerebellobulbospinal involvement.
Methods: Two affected of four (total) offspring of healthy non-consanguineous Anglo-Celtic parents, a female and male aged 46 and 54, were examined clinically, electrophysiologically (NCS, VEP’s, SSEP’s), and by MRI scanning.
Results: On historical grounds, onset was probably in adolescence. Both had a syndrome comprising lower limb distal amyotrophy and weakness superimposed on pyramidal weakness; knee jerks were abnormally brisk but ankle jerks depressed/absent. Motor NCS’s and EMG were consistent with a mild axonal motor neuropathy or a neuronopathy. Both had impaired large-fibre sensory dysfunction in lower > upper limbs (vibration thresholds and 2-point discrimination) with normal SNAP’s but absent SSEP’s. Both had impairment of red-green colour vision, and symmetrical marked prolongation of pattern VEP’s, the more severely affected with optic atrophy. One had slight and the other mild appendicular ataxia. MRI scans in the less affected showed an abnormal increase in T2 signal in the middle cerebellar peduncles, while the more severely affected had the additional findings of increased signal in the white matter tracts of the medulla and spinal cord atrophy. Supratentorial structures (and intellect) were normal. GFAP gene sequencing excluded adult-onset Alexander’s disease.
Conclusion: These two siblings present a unique, slowly-progressive, presumably recessive, opticocerebellobulbospinal leukodystrophy. Ascertainment of other similarly-affected individuals may enable gene identification using homozygosity by descent analysis.