When Neuromotor Delay Meets Thyroid Dysfunction: A Case for Considering Allan–Herndon–Dudley Syndrome

Introduction

Allan–Herndon–Dudley syndrome (AHDS), also known as monocarboxylate transporter 8 (MCT8) deficiency, is a rare neurodevelopmental disorder caused by mutations in the SLC16A2 gene. It follows an X-linked recessive inheritance pattern, primarily affecting males; however, symptomatic female cases have also been reported (Groeneweg S et al. Lancet Diabetes Endocrinol 2020; 8: 594–605; J Clin Endocrinol Metab 2025; dgaf311). To date, nearly 400 affected male individuals have been described in the literature (Visser WE, Orphanet, ORPHA: 59).

MCT8 is a critical transporter protein facilitating the entry of triiodothyronine (T3) across the blood-brain barrier into the central nervous system. Although MCT8 is essential for T3 transport into the brain, the precise identity of the neural and neurovascular cell types requiring MCT8-mediated T3 uptake remains incompletely understood, and this continues to be an active area of research (Wilpert N-M et al. Thyroid 2020; 30: 1366–1383).

Inadequate delivery of thyroid hormone to the central nervous system, particularly during prenatal development and early infancy, can severely impair neurodevelopmental processes (Refetoff S et al. Thyroid 2021; 31: 713–720). The spectrum of neurological involvement in AHDS is broad. While many patients do not achieve key motor milestones such as independent sitting or walking, others may reach partial motor skills or present only with mild movement disorders. At the milder end of the spectrum, some individuals show isolated intellectual disability or action-induced dystonia, without any delay in verbal or gross motor development (Groeneweg S et al. Endocr Rev 2020; 41: 146–201; Wilpert N-M et al. Int J Mol Sci 2024; 25(16): 8585). Increased muscle tone with dystonic posturing of the limbs and neck is frequently observed. Exaggerated deep tendon reflexes and contractures may occur, although their presence and severity vary widely across patients (van Geest F S et al. J Clin Endocrinol Metab 2022; 107: e1136–e1147). In childhood, there is significant cognitive impairment, characterized by a lack of speech development and basic communication skills. This syndrome is associated with high morbidity and mortality rates during childhood (Groeneweg S et al. Lancet Diabetes Endocrinol 2020; 8: 594–605).

Herein, we present a case of AHDS caused by a hemizygous duplication on the X chromosome.

Publikationsverlauf

Artikel online veröffentlicht:
21. November 2025