Allan–Herndon–Dudley syndrome

Allan–Herndon–Dudley Syndrome

Allan–Herndon–Dudley syndrome (AHDS) is an X-linked recessive disorder affecting brain development. This condition predominantly affects males and is characterized by moderate to severe intellectual disability, difficulties with speech, and motor function abnormalities. This article provides a comprehensive overview of its genetics, clinical features, diagnosis, management, and prognosis.

Genetics

AHDS is an X-linked recessive disorder, caused by mutations in the SLC16A2 gene, also known as the MCT8 gene. This gene is crucial for the transport of thyroid hormones into nerve cells in the brain, which are essential for brain development and function.

Clinical Features

• Intellectual Disability: Ranges from moderate to severe.
• Motor Function Abnormalities:
  • Hypotonia (reduced muscle tone) in infancy.
  • Developmental delay in motor milestones.
  • Spasticity and dystonia in later stages.
  • Ataxia or poor coordination.
• Speech Difficulties: Most affected individuals are non-verbal.
• Additional Features:
  • Difficulty swallowing.
  • Muscle wasting.
  • Abnormal posturing.

Diagnosis

• Clinical Assessment: A thorough evaluation of developmental milestones, motor skills, and intellectual abilities.
• Genetic Testing: Identification of mutations in the SLC16A2 gene confirms the diagnosis.
• Thyroid Function Tests: Altered levels of thyroid hormones, especially T3, can be indicative.

Management

There's no cure, but supportive treatment can improve the quality of life:

• Physical therapy for muscle tone and strength.
• Occupational therapy for skills like feeding and dressing.
• Speech therapy to improve communication skills.
• Medications to manage spasticity and other motor symptoms.

Prognosis

The progression of AHDS can vary among individuals. While motor and speech difficulties can be severe, the life expectancy is generally normal. However, due to the significant disabilities, individuals often require lifelong support and care.

Research

Research is ongoing to better understand the disease mechanism, with hopes of developing targeted treatments. Current studies focus on thyroid hormone transport and potential therapies to restore its function in the brain.

See Also

• X-linked recessive inheritance
• Intellectual Disability
• Thyroid hormones

References

• Dumitrescu, A. M., Liao, X. H., Weiss, R. E., Millen, K., & Refetoff, S. (2004). Tissue-specific thyroid hormone deprivation and excess in monocarboxylate transporter (mct) 8-deficient mice. Endocrinology.
• Friesema, E. C., Grueters, A., Biebermann, H., Krude, H., von Moers, A., Reeser, M., ... & Visser, T. J. (2004). Association between mutations in a thyroid hormone transporter and severe X-linked psychomotor retardation. The Lancet.

• GeneReviews/NCBI/NIH/UW entry on MCT8 (SLC16A2)-Specific Thyroid Hormone Cell Transporter Deficiency
• Allan–Herndon–Dudley syndrome at National Library of Medicine

NIH genetic and rare disease info

• NIH info on Allan–Herndon–Dudley syndrome

Allan–Herndon–Dudley syndrome is a rare disease.