Unexpected clinical course in a 9-year-old boy with congenital hypomyelinating neuropathy due to a novel MPZ gene mutation

Objective: To introduce the unexpected clinical course of congenital hypomyelinating neuropathy (CHN) in a boy. Autosomal dominant/recessive CHN manifests usually in the neonatal period, possibly until the second year of life with generalized muscle weakness, -hypotonia, absent tendon reflexes, often complicated by feeding problems and respiratory difficulties. Prognosis is severe leading to death in early infancy; only a few cases are reported with longer survival.

Methods: We describe clinical symptoms, results of 2 nerve biopsies and molecular analysis in a 9-year-old boy with histologically proven CHN.

Results: The patient presented with generalized muscle weakness, -hypotonia, absent tendon reflexes and feeding difficulties since birth. Sensory and motor nerve conduction velocities could not be determined; nerve biopsy at the age of 7 months revealed severe hypomyelination. Unexpectedly the boy shows a still positive psychomotor development. In contrast to the clinical amelioration a second nerve biopsy at the age of 7 years showed more pronounced hypomyelination. Molecular genetic analysis disclosed a novel mutation in the MPZ gene.

Conclusions: In CHN neurophysiological and genetic investigations are of diagnostic value; nerve biopsy confirms more specifically the diagnosis and is mandatory for the differential diagnosis of a Dejerine-Sottas-syndrome. In the first years of life it is difficult to predict the outcome of the individual patient because the phenotype may vary. The clinical course may not be closely correlated with histological changes in the sural nerve which is shown in our patient for the first time by a follow-up nerve biopsy.

Keywords: congenital hypomyelinating neuropathy, MPZ gene mutation