Encephalopathic attacks in a family co-segregating myotonic dystrophy type 1, an intermediate Charcot–Marie–Tooth neuropathy and early hearing loss

• Published in: Journal of neurology, neurosurgery and psychiatry Vol. 80; no. 9; pp. 1029 - 1035
• Main Authors: Spaans, F, Faber, C G, Smeets, H J M, Hofman, P A M, Braida, C, Monckton, D G, de Die-Smulders, C E M
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01.09.2009; BMJ Publishing Group; BMJ Publishing Group LTD
• Subjects: Adult; Age; Aged; Aged, 80 and over; Audiometry, Pure-Tone; Biological and medical sciences; Blotting, Southern; Brain Diseases - etiology; Brain Diseases - genetics; Charcot-Marie-Tooth Disease - complications; Charcot-Marie-Tooth Disease - genetics; Chromosomes; Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction; DNA - genetics; Electrodes; Electroencephalography; Electromyography; Female; Follow-Up Studies; Hearing loss; Hearing Loss - etiology; Humans; Male; Medical sciences; Middle Aged; Nervous system (semeiology, syndromes); Neural Conduction - physiology; Neurology; Patients; Pedigree; Recurrence; Reverse Transcriptase Polymerase Chain Reaction; Neuromuscular diseases; Nervous system diseases; Myotonia; Auditory disorder; Neuropathy; Genetic disease; Hearing loss; Myotonic dystrophy; Charcot-Marie-Tooth disease; Central nervous system disease; ENT disease; Degenerative disease; Spinal cord disease; HMSN (CHARCOT-MARIE-TOOTH); MYOTONIC DYSTROPHY
• ISSN: 0022-3050; 1468-330X; 1468-330X
• DOI: 10.1136/jnnp.2008.170126

Objective:To report new disease components in a unique myotonic dystrophy type 1 (DM1) family previously described by us in which all affected members also had a sensorimotor neuropathy that co-segregated with markers flanking the DM1 locus.Methods:Clinical observations, electrophysiology, audiometry, DNA studies.Results:During a follow-up period of over 25 years, the following were observed: (i) co-segregation of a striking new encephalopathic phenotype. In middle age, five patients were admitted on multiple occasions with attacks of impaired consciousness, psychomotor agitation, fever and, in about half of the cases, focal neurological signs, including unilateral weakness, sensory deficits and dysphasia. Reported onset phenomena consisted of confusion, headache, focal neurological symptoms and nausea; (ii) many patients show an early and severe sensorineural hearing loss; (iii) although they have mothers with the adult onset type, the four affected subjects from the youngest generation do not show any signs or symptoms of childhood or congenital myotonic dystrophy; (iv) the neuropathy meets the criteria of an intermediate type Charcot–Marie–Tooth (CMT), and is more severe in males; and (v) patients presented with an expanded fragment at the DM1 CTG repeat but this allele was refractory to PCR amplification and triplet repeat primed PCR at the 3′ end of the array, indicating the existence of an additional lesion at the 3′ end.Conclusions:The phenotype in this unique family extends beyond myotonic dystrophy and CMT to include encephalopathic attacks and early hearing loss, and is associated with an atypical mutation at the DM1 locus.