Myelination Delay and Allan-Herndon-Dudley Syndrome Caused by a Novel Mutation in the SLC16A2 Gene

Abstract

Allan-Herndon-Dudley syndrome is an X-linked disease caused by mutations in the solute carrier family 16 member 2 (SLC16A2) gene. As SLC16A2 encodes the monocarboxylate transporter 8 (MCT8), a thyroid hormone transporter, patients with Allan-Herndon-Dudley syndrome present a specific altered thyroid hormone profile. Allan-Herndon-Dudley syndrome has been associated with myelination delay on the brain magnetic resonance imaging (MRI) of affected subjects. We report a patient with Allan-Herndon-Dudley syndrome characterized by developmental delay, hypotonia, and delayed myelination caused by a novel SLC16A2 mutation (p.L291R). The thyroid hormones profile in our patient was atypical for Allan-Herndon-Dudley syndrome. The follow-up examinations showed that the progression of the myelination was not accompanied by a clinical improvement. Our paper suggests that SLC16A2 mutations should be investigated in patients with myelination delay even when the thyroid function is not conclusively altered.

Keywords

myelination delay thyroid function Allan-Herndon-Dudley syndrome

Get full access to this article

View all access options for this article.

References

Frints

Lenzner

Bauters

. MCT8 mutation analysis and identification of the first female with Allan-Herndon-Dudley syndrome due to loss of MCT8 expression. Eur J Hum Genet. 2008;16:1029–1037.

Dumitrescu

Liao

Best

Brockmann

Refetoff

. A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene. Am J Hum Genet. 2004;74:168–175.

Schwartz

May

Carpenter

. Allan-Herndon-Dudley syndrome and the monocarboxylate transporter 8 (MCT8) gene. Am J Hum Genet. 2005;77:41–53.

Friesema

ECH

Grueters

Biebermann

. Association between mutations in a thyroid hormone transporter and severe X-linked psychomotor retardation. Lancet. 2004;364:1435–1437.

Holden

Zuniga

May

. X-linked MCT8 gene mutations: characterization of the pediatric neurologic phenotype. J Child Neurol. 2005;20:852–857.

Namba

Etani

Kitaoka

. Clinical phenotype and endocrinological investigations in a patient with a mutation in the MCT8 thyroid hormone transporter. Eur J Pediatr. 2008;167:785–791.

Papadimitriou

Dumitrescu

Papavasiliou

Fretzayas

Nicolaidou

Refetoff

. A novel monocarboxylate transporter 8 gene mutation as a cause of severe neonatal hypotonia and developmental delay. Pediatrics. 2008;121:e199–e202.

Gika

Siddiqui

Hulse

. White matter abnormalities and dystonic motor disorder associated with mutations in the SLC16A2 gene. Dev Med Child Neurol. 2010;52:475–482.

Vaurs-Barriere

Deville

Sarret

. Pelizaeus-Merzbacher-Like disease presentation of MCT8 mutated male subjects. Ann Neurol. 2009;65:114–118.

10.

van der Knaap

Wolf

. Hypomyelination versus delayed myelination. Ann Neurol. 2010;68:115.

11.

Schiffmann

van der Knaap

. Invited article: an MRI-based approach to the diagnosis of white matter disorders. Neurology. 2009;72:750–759.

12.

Younes-Rapozo

Berendonk

Savignon

Manhaes

Barradas

. Thyroid hormone deficiency changes the distribution of oligodendrocyte/myelin markers during oligodendroglial differentiation in vitro. Int J Dev Neurosci. 2006;24:445–453.

13.

Trajkovic

Visser

Mittag

. Abnormal thyroid hormone metabolism in mice lacking the monocarboxylate transporter 8. J Clin Invest. 2007;117:627–635.

14.

Tonduti

Vanderver

Berardinelli

. MCT8 deficiency: extrapyramidal symptoms and delayed myelination as prominent features. J Child Neurol. 2013;28:792–797.

15.

Refetoff

Dumitrescu

. Syndromes of reduced sensitivity to thyroid hormone: genetic defects in hormone receptors, cell transporters and deiodination. Best Pract Res Clin Endocrinol Metab. 2007;21:277–305.