Centronuclear myopathy with cataracts due to a novel dynamin 2 (DNM2) mutation.

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Neuromuscul Disord. 2009 Nov 20

Centronuclear myopathy with cataracts due to a novel dynamin 2 (DNM2) mutation.

Jungbluth H, Cullup T, Lillis S, Zhou H, Abbs S, Sewry C, Muntoni F.

Clinical Neuroscience Division, King's College, London, UK; Department of

Paediatric Neurology, Neuromuscular Service, Evelina Children's Hospital, Guy's

& St. ' NHS Foundation Trust, London, UK.

Dynamin 2 (DNM2)-related dominant centronuclear myopathy is usually a mild

disorder, but more severe variants have been associated with mutations affecting

the pleckstrin homology (PH) domain of the protein, mainly implicated in

different forms of Charcot-Marie-Tooth Disease (CMT).

Whilst implicated in different forms of Charcot-Marie-Tooth Disease (CMT).

DNM2-related CMT may feature non-neurological findings including cataracts, this

has not been reported in DNM2-related centronuclear myopathy.

We report a girl presenting from birth with hypotonia, respiratory and feeding

difficulties. Motor development was delayed and at 9years she lost the ability

to walk. She had ptosis, external ophthalmoplegia and bilateral cataracts.

Muscle biopsy showed increase in central nuclei with type 1 hypotrophy and

fibrosis. DNM2 screening revealed a novel heterozygous substitution (c.1862T>C;

p.Leu621Pro) affecting the PH domain of the protein.

Her further course was progressive and at 14 years she died from respiratory

failure. Our findings expand the phenotypical spectrum associated with DNM2

mutations and provide a new clinical indicator for involvement of this gene in

patients with centronuclear myopathy.