X-Linked MCT8 Gene Mutations: Characterization of the Pediatric Neurologic Phenotype

Greenwood Genetic Center, Greenwood, SC, USA.
Journal of Child Neurology (Impact Factor: 1.72). 11/2005; 20(10):852-7. DOI: 10.1177/08830738050200101601
Source: PubMed


We report a family with X-linked mental retardation that has a novel mutation in the monocarboxylate transporter 8 (MCT8) gene associated with a characteristic neurodevelopmental phenotype with early childhood hypotonia that progresses to spasticity and global developmental delays. Affected patients experience moderate to severe psychomotor delays and congenital hypotonia, develop a myopathic facies, have diminished muscle bulk and generalized muscle weakness, develop progressive spasticity and movement disorders, and have limited speech but alert, affable personalities. Acquired microcephaly and abnormal myelination on brain magnetic resonance imaging can be present. Normal monocarboxylate transporter 8 gene functioning appears to be necessary for normal thyroid-associated metabolism in neurons. Abnormal thyroid function tests appear to be a consistent finding in the absence of typical signs of thyroid dysfunction. Although the phenotype appears to be consistent, and although the neurotoxic effects of abnormal central and peripheral neuromuscular system thyroid metabolism might be partly or wholly responsible for the neurologic phenotype reported, the exact mechanism remains unclear.

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    • "In addition to the clinical and biological features of patients with SLC16A2 mutations, some authors have reported a nonspecific myelination delay [Holden et al., 2005; Namba et al., 2008] and spectroscopic abnormalities [Sijens et al., 2008]. More recently, the identification of SLC16A2 mutations in a series of patients initially considered as presenting with a severe Pelizaeus–Merzbacher-like disease (PMD) in their first years of life has confirmed this association with delayed myelination [Gika et al., 2010; Vaurs - Barrì ere et al., 2009] . "
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