title: White matter abnormalities and dystonic motor disorder associated with mutations in the SLC16A2 gene.
abstract: 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.
authors.affiliation: Department of Paediatric Neurology, Evelina Children's Hospital, Guy's & St Thomas' NHS Foundation Trust, London, UK.
authors.forename: Artemis D
authors.initials: AD
authors.lastname: Gika
authors.forename: Ata
authors.initials: A
authors.lastname: Siddiqui
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Hulse
authors.forename: Selvakumari
authors.initials: S
authors.lastname: Edward
authors.forename: Penny
authors.initials: P
authors.lastname: Fallon
authors.forename: Meriel E
authors.initials: ME
authors.lastname: McEntagart
authors.forename: Wajanat
authors.initials: W
authors.lastname: Jan
authors.forename: Dragana
authors.initials: D
authors.lastname: Josifova
authors.forename: Tally
authors.initials: T
authors.lastname: Lerman-Sagie
authors.forename: James
authors.initials: J
authors.lastname: Drummond
authors.forename: Edward
authors.initials: E
authors.lastname: Thompson
authors.forename: Samuel
authors.initials: S
authors.lastname: Refetoff
authors.forename: Carsten G
authors.initials: CG
authors.lastname: Bönnemann
authors.forename: Heinz
authors.initials: H
authors.lastname: Jungbluth
mesh_terms: 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
chemical_list: D027501:Monocarboxylic Acid Transporters; C090735:SLC16A2 protein, human; D027981:Symporters; D014284:Triiodothyronine