White matter abnormalities and dystonic motor disorder associated with mutations in the SLC16A2 gene

• Published in: Developmental medicine and child neurology 2010-05, Vol.52 (5), p.475-482
• Main Authors: GIKA, ARTEMIS D, SIDDIQUI, ATA, HULSE, ANTHONY J, EDWARD, SELVAKUMARI, FALLON, PENNY, MCENTAGART, MERIEL E, JAN, WAJANAT, JOSIFOVA, DRAGANA, LERMAN‐SAGIE, TALLY, DRUMMOND, JAMES, THOMPSON, EDWARD, REFETOFF, SAMUEL, BÖNNEMANN, CARSTEN G, JUNGBLUTH, HEINZ
• Format: Article
• Language: English
• Subjects: Brain; Brain - pathology; Cerebral Palsy; Child, Preschool; Children; Clinical Diagnosis; Cohort Studies; Developmental Delays; Diagnosis, Differential; Dystonic Disorders - blood; Dystonic Disorders - diagnosis; Dystonic Disorders - genetics; Dystonic Disorders - pathology; Evaluation Methods; Family (Sociological Unit); Genetic Disorders; Humans; Infant; Learning Disabilities; Learning Disorders - genetics; Learning Disorders - pathology; Magnetic Resonance Imaging; Male; Males; Mental Retardation; Monocarboxylic Acid Transporters - genetics; Movement Disorders - genetics; Movement Disorders - pathology; Mutation; Nerve Fibers, Myelinated - pathology; Neurological Impairments; Older Adults; Parents; Pregnancy; Retrospective Studies; Science Education; Screening Tests; Spectroscopy; Syndrome; Triiodothyronine - blood
• ISSN: 0012-1622; 1469-8749
• DOI: 10.1111/j.1469-8749.2009.03471.x

Aim  Mutations in the SLC16A2 gene have been implicated in Allan–Herndon–Dudley syndrome (AHDS), an X‐linked learning disability* syndrome associated with thyroid function test (TFT) abnormalities. Delayed myelination is a non‐specific finding in individuals with learning disability whose genetic basis is often uncertain. The aim of this study was to describe neuroimaging findings and neurological features in males with SLC16A2 gene mutations. Method  We reviewed brain magnetic resonance imaging (MRI) findings and neurological features in a cohort of five males aged between 1 year 6 months and 6 years (median 4y) from four families harbouring SLC16A2 gene mutations. Results  The participants presented aged between 4 and 9 months with initial hypotonia and subsequent spastic paraparesis with dystonic posturing and superimposed paroxysmal dyskinesias. Dystonic cerebral palsy was the most common initial clinical diagnosis, and AHDS was suspected only retrospectively, considering the characteristically abnormal thyroid function tests, with high serum tri‐iodothyronine (T3), as the most consistent finding. Brain MRI showed absent or markedly delayed myelination in all five participants, prompting the suspicion of Pelizaeus–Merzbacher disease in one patient. Interpretation  Our findings indicate a consistent association between defective neuronal T3 uptake and delayed myelination. SLC16A2 involvement should be considered in males with learning disability, an associated motor or movement disorder, and evidence of delayed myelination on brain MRI. Although dysmorphic features suggestive of AHDS are not always present, T3 measurement is a reliable screening test.