Intermediate CMT: Encephalopathic attacks in a family co-segregating myotonic dy

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J Neurol Neurosurg Psychiatry. 2009 Mar 24.

Encephalopathic attacks in a family co-segregating myotonic dystrophy type 1, an

intermediate Charcot-Marie-Tooth neuropathy and early hearing loss.

Spaans F, Faber CG, Smeets HJ, Hofman PA, Braida C, Monckton DG, de Die CE.

Maastricht University Medical Centre, Netherlands.

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, we observed: i) The

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 neurologic signs, including unilateral weakness, sensory deficits and

dysphasia. Reported onset phenomena consisted of confusion, headache, focal

neurologic 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 of myotonic dystrophy. iv)

The neuropathy meets the criteria of an intermediate type Charcot-Marie-Tooth,

and is more severe in the 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.