Genetic disorders of thyroid metabolism and brain development

Abstract

Normal thyroid metabolism is essential for human development, including the formation and functioning of the central and peripheral nervous system. Disorders of thyroid metabolism are increasingly recognized within the spectrum of paediatric neurological disorders. Both hypothyroid and hyperthyroid disease states (resulting from genetic and acquired aetiologies) can lead to characteristic neurological syndromes, with cognitive delay, extrapyramidal movement disorders, neuropsychiatric symptoms, and neuromuscular manifestations. In this review, the neurological manifestations of genetic disorders of thyroid metabolism are outlined, with particular focus on Allan-Herndon-Dudley syndrome and benign hereditary chorea. We report in detail the clinical features, major neurological and neuropsychiatric manifestations, molecular genetic findings, disease mechanisms, and therapeutic strategies for these emerging genetic 'brain-thyroid' disorders.

Figure 1

A 4-year-old patient with genetically confirmed Allan-Herndon-Dudley syndrome, with photographs illustrating (a) face/trunk/limbs (b) facial features and (c) lateral facial view. Note the typical but subtle dysmorphic features, including myopathic facial appearance with inverted V-shaped mouth, low anterior hairline, narrow forehead, receding chin, and large, low-set ears. From Gika et al., with permission.