Hereditary motor and sensory neuropathy--Lom, a novel demyelinating neuropathy associated with deafness in gypsies. Clinical, electrophysiological and nerve biopsy findings

• Published in: Brain (London, England : 1878) Vol. 121; no. 3; pp. 399 - 408
• Main Author: Kalaydjieva, L
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.03.1998; Oxford Publishing Limited (England)
• Subjects: Adolescent; Adult; Biological and medical sciences; Biopsy; Carrier State - physiopathology; Child; Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction; Deafness - complications; Demyelinating Diseases - complications; Demyelinating Diseases - pathology; Demyelinating Diseases - physiopathology; Electrophysiology; Female; Hearing - physiology; Hereditary Sensory and Motor Neuropathy - complications; Hereditary Sensory and Motor Neuropathy - pathology; Hereditary Sensory and Motor Neuropathy - physiopathology; Humans; Male; Medical sciences; Microscopy, Electron; Middle Aged; Nervous system (semeiology, syndromes); Neural Conduction - physiology; Neurology; Sural Nerve - pathology; Tropical medicine; Human; Nervous system diseases; Auditory disorder; Genetic determinism; Genetic disease; Hearing loss; Pathology; Electrodiagnosis; Nerve conduction; Sensorimotor peripheral polyneuropathy; Biopsy; Demyelination; Autosomal character; Auditory evoked potential; Young adult; ENT disease; Recessive character; Peripheral nerve disease; Diagnosis; Child; Sural nerve
• ISSN: 1460-2156; 0006-8950; 1460-2156
• DOI: 10.1093/brain/121.3.399

A previously unrecognized neuropathy was identified in Bulgarian gypsies, and was designated hereditary motor and sensory neuropathy-Lom (HMSNL) after the town where the initial cases were found. It was subsequently identified in other gypsy communities. The disorder, which is of autosomal recessive inheritance, was mapped to chromosome 8q24. It begins consistently in the first decade of life with gait disorder followed by upper limb weakness in the second decade and, in most subjects, by deafness which is most often first noticed in the third decade. Sensory loss affecting all modalities is present, both this and the motor involvement predominating distally in the limbs. Skeletal deformity, particularly foot deformity, is frequent. Severely reduced motor nerve conduction velocity indicates a demyelinating basis, which was confirmed by nerve biopsy. The three younger patients biopsied showed a hypertrophic 'onion bulb' neuropathy. The hypertrophic changes were not evident in the oldest individual biopsied and it is likely that they had regressed secondarily to axon loss. In the eight cases in which brainstem auditory evoked potentials could be recorded, the results suggested demyelination in the eighth cranial nerve and also abnormal conduction in the central auditory pathways in the brainstem. As no myelin genes are known to be located at chromosome 8q24, the disorder may involve a gene for a novel myelin protein or be due to an abnormality of axon-Schwann cell signalling.