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Expanding the phenotypic spectrum of Allan–Herndon–Dudley syndrome in patients with SLC 16A2 mutations
- Source :
- Developmental Medicine and Child Neurology, Developmental Medicine and Child Neurology, Wiley-Blackwell, 2019, 61 (12), pp.1439-1447. ⟨10.1111/dmcn.14332⟩, Developmental Medicine and Child Neurology, 2019, 61 (12), pp.1439-1447. ⟨10.1111/dmcn.14332⟩
- Publication Year :
- 2019
- Publisher :
- HAL CCSD, 2019.
-
Abstract
- The aim of the study was to redefine the phenotype of Allan-Herndon-Dudley syndrome (AHDS), which is caused by mutations in the SLC16A2 gene that encodes the brain transporter of thyroid hormones. Clinical phenotypes, brain imaging, thyroid hormone profiles, and genetic data were compared to the existing literature. Twenty-four males aged 11 months to 29 years had a mutation in SLC16A2, including 12 novel mutations and five previously described mutations. Sixteen patients presented with profound developmental delay, three had severe intellectual disability with poor language and walking with an aid, four had moderate intellectual disability with language and walking abilities, and one had mild intellectual disability with hypotonia. Overall, eight had learned to walk, all had hypotonia, 17 had spasticity, 18 had dystonia, 12 had choreoathetosis, 19 had hypomyelination, and 10 had brain atrophy. Kyphoscoliosis (n=12), seizures (n=7), and pneumopathies (n=5) were the most severe complications. This study extends the phenotypic spectrum of AHDS to a mild intellectual disability with hypotonia. Developmental delay, hypotonia, hypomyelination, and thyroid hormone profile help to diagnose patients. Clinical course depends on initial severity, with stable acquisition after infancy; this may be adversely affected by neuro-orthopaedic, pulmonary, and epileptic complications. WHAT THIS PAPER ADDS: Mild intellectual disability is associated with SLC16A2 mutations. A thyroid hormone profile with a free T3 /T4 ratio higher than 0.75 can help diagnose patients. Patients with SLC16A2 mutations present a broad spectrum of neurological phenotypes that are also observed in other hypomyelinating disorders. Axial hypotonia is a consistent feature of Allan-Herndon-Dudley syndrome and leads to specific complications.
- Subjects :
- 030506 rehabilitation
Pediatrics
medicine.medical_specialty
Muscle Hypotonia
[SDV]Life Sciences [q-bio]
Choreoathetosis
03 medical and health sciences
0302 clinical medicine
Atrophy
Developmental Neuroscience
Intellectual disability
medicine
Kyphoscoliosis
ComputingMilieux_MISCELLANEOUS
Dystonia
Allan–Herndon–Dudley syndrome
[SDV.GEN]Life Sciences [q-bio]/Genetics
business.industry
medicine.disease
Hypotonia
3. Good health
[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics
Pediatrics, Perinatology and Child Health
Neurology (clinical)
medicine.symptom
0305 other medical science
business
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 00121622
- Database :
- OpenAIRE
- Journal :
- Developmental Medicine and Child Neurology, Developmental Medicine and Child Neurology, Wiley-Blackwell, 2019, 61 (12), pp.1439-1447. ⟨10.1111/dmcn.14332⟩, Developmental Medicine and Child Neurology, 2019, 61 (12), pp.1439-1447. ⟨10.1111/dmcn.14332⟩
- Accession number :
- edsair.doi.dedup.....c6517115e7effb7d3ca5d34975f32d8b