X-LINKED PSYCHOMOTOR DELAY AND ELEVATED SERUM T3 LEVELS CAUSED BY MUTATIONS IN THE MCT8 GENE: DELINEATION OF THE CLINICAL SYNDROME

Objectives: Deficient transport of triiodothyronine (T3) into foetal and neonatal brain cells due to abnormalities of the monocarboxylate transporter 8 (MCT8) gene (Xq13.2) has recently been described as a cause for severe psychomotor retardation in boys. This presentation aims to delineate the neurological syndrome of these patients.

Methods: The clinical signs of the five boys described by Friesema et al. (Lancet 2004,364,1435) and four additional boys will be detailed and compared with two patients described by Dumitrescu et al (Am J Hum Genet 2004,74,168) and with patients with Allen-Herndon-Dudley (AHD) syndrome (Schwartz et al, Am J Hum Genet 2005,77,41).

Results: The main dysmorphic feature in our patients is secondary microcephaly. Minor facial dysmorphisms are sometimes seen. Apart from delay of motor and mental development, neurological signs comprise profound axial hypotonia with pyramidal and pseudobulbar signs; dystonic posturing and movements often elicited by sensory stimuli; complete absence of speech development with intact hearing; secondarily generalized seizures. One child died after two severe dystonic crises. MRI scans show generalized brain atrophy, delayed myelination and subtle white matter abnormalities, but also apparently normal findings. Differences in clinical severity are probably related to the type of mutation, leaving varying residual functionality of the remaining MCT8 protein.

Conclusion: Varying combinations of retardation, absence of speech development, dystonic posturing and movements and secondary microcephaly in boys should prompt the physician to look for elevated serum T3 levels, the most sensitive laboratory parameter for a MCT8 mutation. We recommend adding serum T3 determination to screening programs for the analysis of unexplained developmental delay.