Hereditary motor and sensory neuropathy Lom (HMSNL) is a severe form of demyelinating Charcot-Marie-Tooth (CMT) disease, associated with neural deafness in the majority of affected individuals. All known cases are of Romani (Gypsy) background. In Bulgaria, the average gene frequency for the entire Romani population has been estimated at about 1.5%. The onset of the disease is at age 4-10 years. Diagnosis criteria include severe demyelinating neuropathy, severe reduction of nerve conduction velocities and of myelinated fibre density, and extensive endoneurial collagen deposition. The HMSNL phenotype is consistent and shows limited variation. Gait disturbances, with easy fatigue, frequent stumbling and falling are the first symptoms. Difficulties in using the hands become apparent at 5-15 years of age. Distally accentuated muscle weakness and wasting develop rapidly and are particularly severe in the lower limbs. Sensory loss involving all modalities is also distally accentuated and most evident in the lower limbs. Neural deafness develops between 15 and 30 years of age. HMSNL is transmitted as an autosomal recessive trait. The disorder is caused by a single ancestral mutation (R148X) in the N-myc downstream-regulated gene 1 (NDRG1), mapped to chromosome 8q24 and with hypothetical functions in growth arrest and cell differentiation. All HMSNL individuals investigated to date are homozygous for the NDRG1 mutation, making molecular diagnosis straightforward and unambiguous. Apart from orthopedic surgery for the correction of deformities, no treatment is available.
Last update: January 2004