CMT 1A / HMSN 1A with autism - Netherlands research

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Research from Genet Couns. 2004;15(1):73-80.

Hereditary motor and sensory neuropathy (HMSN) IA, developmental delay

and autism related disorder in a boy with duplication (17)(p11.2p12).

Moog U, Engelen JJ, Weber BW, Van Gelderen M, Steyaert J, Baas F,

Sijstermans HM, Fryns JP.

Department of Clinical Genetics, Research Institute Growth & Development

(GROW), Maastricht University, Maastricht, The Netherlands.

We present a 6-year-old boy with moderate developmental delay, gait

disturbance, autism related disorder and mild dysmorphic features. He

was seen for evaluation of his retardation since the age of 2.8 years.

At first sight, a cytogenetic analysis showed a normal 46,XY karyotype.

Neurological examination at the age of 5.5 years revealed a motor and

sensory polyneuropathy. A quantitative Southern blot with probes PMP22

and VAW409 specific for Charcot-Marie-Tooth type 1 (CMT1) disclosed a

duplication which confirmed the diagnosis HMSN Ia. Subsequently, GTG

banded metaphases were re-evaluated and a small duplication 17p was seen

on retrospect. Additional FISH with probe LSISMS (Vysis) specific for

the -Magenis region at 17p11.2 again showed a duplication. Both

parents had a normal karyotype and the duplication test for CMT1 showed

normal results for both of them. The boy had a de novo

46,XY,dup(17)(p11.2p12) karyotype. The present observation confirms

previous findings of mild psychomotor delay, neurobehavioural features

and minor craniofacial anomalies as the major phenotypic features of

dup(17)(p11.2) and dup(17)(p11.2p12); in cases of duplications

comprising the PMP22 locus HMSN1 is associated. A recognizable facial

phenotype emerges characterized by a broad forehead, hypertelorism,

downslant of palpebral fissures, smooth philtrum, thin upper lip and ear

anomalies.