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

Artemis D. Gika, Ata Siddiqui, Anthony J. Hulse, Selvakumari Edward, Penny Fallon, Meriel E. Mcentagart, Wajanat Jan, Dragana Josifova, Tally Lerman-Sagie, James Drummond, Edward Thompson, Samuel Refetoff, Carsten G. Bönnemann, Heinz Jungbluth*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)475-482
Number of pages8
JournalDevelopmental Medicine and Child Neurology
Issue number5
StatePublished - May 2010
Externally publishedYes


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