A 7‐month‐old male with Allan‐Herndon‐Dudley syndrome and the power of T3

Langley, Katherine G.; Trau, Steven P.; Bean, Lora Jh; Narravula, Alekhya; Vergano, Samantha A. Schrier

doi:10.1002/ajmg.a.36970

Cited by 7 publications

(9 citation statements)

References 17 publications

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“…We also found frequent slowness, muscle weakness, and prehension difficulties. These symptoms are probably favoured by relative peripheral dysthyroidism …”

Section: Discussionmentioning

confidence: 99%

“…These symptoms are probably favoured by relative peripheral dysthyroidism. 4,5,7,10,12,13,15,16,21,[52][53][54][55][56][57][58] Spasticity and lower-limb hyperreflexia are classical and frequent signs in AHDS. 1,4,[7][8][9][10][12][13][14][15][16]21,[27][28][29][30][31][33][34][35][36][37][38][39][40][41][42][43][45][46][47][48][49][50][52][53]…”

Section: Discussionmentioning

confidence: 99%

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Expanding the phenotypic spectrum of Allan–Herndon–Dudley syndrome in patients with SLC16A2 mutations

Remerand

Boespflug‐Tanguy

Tonduti

et al. 2019

Develop Med Child Neuro

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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.

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“…We also found frequent slowness, muscle weakness, and prehension difficulties. These symptoms are probably favoured by relative peripheral dysthyroidism …”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Expanding the phenotypic spectrum of Allan–Herndon–Dudley syndrome in patients with SLC16A2 mutations

Remerand

Boespflug‐Tanguy

Tonduti

et al. 2019

Develop Med Child Neuro

View full text Add to dashboard Cite

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“…Many kinds of mutations in the SLC16A2 gene have been reported, ranging from single base pair substitutions to deletions of entire exons, both inherited and de novo . A correlation between the SLC16A2 genotype and the severity of the patient's phenotype due to T 3 abnormalities has been proved.…”

Section: Allan–herndon–dudley Syndrome (Slc16a2 Related Disorder) — Amentioning

confidence: 99%

Hypomyelinating leukodystrophies — a molecular insight into the white matter pathology

Charzewska¹,

Wierzba

Iżycka‐Świeszewska

et al. 2016

Clinical Genetics

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Hypomyelinating leukodystrophies (HLDs) are a group of neurodevelopmental disorders that affect proper formation of the myelin sheath in the central nervous system. They are characterized by developmental delay, hypotonia, spasticity, and variable intellectual disability. In the past various classification systems for HLDs have been used, based on imaging findings, clinical manifestation, and organelle-specific disorders. Here we present a molecular insight into HLDs based on a defect in specific gene engaged in myelination. We discuss recent findings on pathogenesis, clinical presentation, and imaging related to these disorders. We focus on HLDs that are in use in differential diagnostics of Pelizaeus-Merzbacher disease (PMD), with a special emphasis on Allan-Herndon-Dudley syndrome (AHDS), an X-linked condition with delayed myelination due to thyroid transport disturbances. On the background of previously published patients we describe a proband initially considered as presenting with a severe PMD, whose diagnosis of AHDS due to a novel nonsense SLC16A2 mutation unraveled two previously undiagnosed generations of affected males who died in infancy from unexplained reasons. Since AHDS is found to be a relatively frequent cause of X-linked intellectual disability, we emphasize the need for determining the whole thyroid profile especially in hypotonic males with a delay of psychomotor development.

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“…Besides allowing an early diagnosis and appropriate genetic counseling, this measure could reduce the extra costs involved in unnecessary complementary diagnostic tests. 28,29 …”

Section: Discussionmentioning

confidence: 99%

Severe neurological abnormalities in a young boy with impaired thyroid hormone sensitivity due to a novel mutation in the MCT8 gene

Rego

Lado

Rodríguez

et al. 2017

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Monocarboxylate transporter 8 (MCT8) is an active and specific thyroid hormone transporter into neurons. MCT8 mutations cause an X-linked condition known as Allan-Herndon-Dudley syndrome and are characterized by impaired psychomotor development and typical abnormal thyroid function. we describe a 10-year-old boy with severe cognitive disability, axial hypotonia, spastic quadriplegia and sporadic dyskinetic episodes. He initially presented with thyroid dysfunction (high FT3, low rT3, low FT4 and normal TSH) and generalized retardation of the cerebral and cerebellar myelination in brain magnetic resonance imaging. The clinical and laboratory findings led to sequencing of the SLC16A2/MCT8 gene, which identified a novel missense mutation in exon 5. The study of peripheral markers of thyroid function suggests a paradoxical state of thyrotoxicosis in some peripheral tissues. Our patient had a typical clinical presentation at birth but because of the rarity of his disease his diagnosis was not made until the age of 7. The delay can also be explained by the omission of the free T3 assay in the first thyroid evaluation performed. This case therefore highlights the possible benefit of including the T3 assay in the study of patients with severe psychomotor disability of unknown etiology, thus eliminating extra costs for unnecessary complementary diagnostic tests.

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A 7‐month‐old male with Allan‐Herndon‐Dudley syndrome and the power of T3

Cited by 7 publications

References 17 publications

Expanding the phenotypic spectrum of Allan–Herndon–Dudley syndrome in patients with SLC16A2 mutations

Expanding the phenotypic spectrum of Allan–Herndon–Dudley syndrome in patients with SLC16A2 mutations

Hypomyelinating leukodystrophies — a molecular insight into the white matter pathology

Severe neurological abnormalities in a young boy with impaired thyroid hormone sensitivity due to a novel mutation in the MCT8 gene

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