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


METHODS
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 (T(3)), 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.


CONCLUSIONS
Our findings indicate a consistent association between defective neuronal T(3) 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, T(3) measurement is a reliable screening test.
Gika
Artemis D
AD
Department of Paediatric Neurology, Evelina Children's Hospital, Guy's & St Thomas' NHS Foundation Trust, London, UK.
Siddiqui
Ata
A
Hulse
Anthony J
AJ
Edward
Selvakumari
S
Fallon
Penny
P
McEntagart
Meriel E
ME
Jan
Wajanat
W
Josifova
Dragana
D
Lerman-Sagie
Tally
T
Drummond
James
J
Thompson
Edward
E
Refetoff
Samuel
S
Bönnemann
Carsten G
CG
Jungbluth
Heinz
H
D001921:Brain / Q000473:pathology*; D002675:Child, Preschool; D015331:Cohort Studies; D003937:Diagnosis, Differential; D020821:Dystonic Disorders / Q000097:blood / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007223:Infant; D007859:Learning Disabilities / Q000235:genetics* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D027501:Monocarboxylic Acid Transporters / Q000235:genetics*; D009069:Movement Disorders / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D012189:Retrospective Studies; D027981:Symporters; D013577:Syndrome; D014284:Triiodothyronine / Q000097:blood
D027501:Monocarboxylic Acid Transporters; C090735:SLC16A2 protein, human; D027981:Symporters; D014284:Triiodothyronine