Centre de Compétence des Leucodystrophies et Leucoencéphalopathies de Cause Rare, Pôle Femme et Enfant, Hôpital Estaing, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France.
Centre de Référence des Leucodystrophies et Leucoencéphalopathies de Cause Rare, Service de Neurologie Pédiatrique, Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris, Paris, France.
Dev Med Child Neurol. 2019 Dec;61(12):1439-1447. doi: 10.1111/dmcn.14332. Epub 2019 Aug 13.
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 T /T 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.
本研究旨在重新定义 Allan-Herndon-Dudley 综合征（AHDS）的表型，该综合征是由 SLC16A2 基因突变引起的，该基因编码甲状腺激素的脑转运体。将临床表型、脑成像、甲状腺激素谱和遗传数据与现有文献进行了比较。24 名年龄在 11 个月至 29 岁的男性携带 SLC16A2 基因突变，包括 12 个新突变和 5 个先前描述的突变。16 名患者表现为严重的发育迟缓，3 名患者严重智力残疾，语言和行走能力差，需借助辅助工具，4 名患者中度智力残疾，语言和行走能力正常，1 名患者轻度智力残疾，伴有张力减退。总的来说，有 8 名患者学会了行走，所有患者均存在张力减退，17 名患者存在痉挛，18 名患者存在肌张力障碍，12 名患者存在舞蹈手足徐动症，19 名患者存在脱髓鞘，10 名患者存在脑萎缩。脊柱侧凸后凸（n=12）、癫痫发作（n=7）和肺部疾病（n=5）是最严重的并发症。本研究将 AHDS 的表型谱扩展至伴有张力减退的轻度智力残疾。发育迟缓、张力减退、脱髓鞘和甲状腺激素谱有助于诊断患者。临床病程取决于初始严重程度，婴儿期后稳定进展；神经矫形、肺部和癫痫并发症可能会使病程恶化。本文的附加信息：SLC16A2 基因突变与轻度智力残疾相关。游离 T/T 比值高于 0.75 的甲状腺激素谱有助于诊断患者。携带 SLC16A2 基因突变的患者表现出广泛的神经表型，这些表型也见于其他脱髓鞘疾病。轴向张力减退是 Allan-Herndon-Dudley 综合征的一个特征性表现，可导致特定的并发症。
