Allan-Herndon-Dudley syndrome

Allan-Herndon-Dudley syndrome is a neurodevelopmental disorder characterized by significant neuromuscular impairment and severe cognitive deficiency. It is caused by alterations in the SLC16A2 gene, which plays a critical role in thyroid hormone transport within the brain and other tissues. The condition primarily affects males due to its X-linked inheritance, with affected individuals typically presenting in infancy with hypotonia and developmental delays. Prevalence data are not well established, and the overall frequency of this condition remains unknown.

Individuals with Allan-Herndon-Dudley syndrome often present with profound intellectual disability and marked axial hypotonia, which are among the most frequently reported features. Neurological findings such as ataxia, spasticity, and choreoathetosis are observed in a significant number of cases, and many affected individuals also exhibit dystonia and hyperreflexia. In addition to these central nervous system manifestations, other clinical features include musculoskeletal concerns like pes planus, pectus excavatum, and kyphoscoliosis, as well as thyroid abnormalities such as increased circulating free T3 and abnormal thyroid physiology. Not all individuals experience all these features, and severity varies considerably.

Allan-Herndon-Dudley syndrome is caused by pathogenic variants in the SLC16A2 gene, which encodes a protein responsible for transporting thyroid hormones into cells. Disruption of this protein’s function interferes with normal thyroid hormone distribution, having a profound impact on brain development and neuromuscular function. The condition is inherited in an X-linked pattern, meaning that affected males inherit the pathogenic variant from their mothers, who may experience mild symptoms due to skewed X-inactivation. Genetic counseling is advised for families to better understand the inheritance pattern and implications for future family planning.

Currently, management of Allan-Herndon-Dudley syndrome focuses on supportive care and symptom management, as no treatments have been specifically approved for this condition. Management is tailored to each individual and typically involves a multidisciplinary team to address neurological, musculoskeletal, and thyroid-related challenges. Regular surveillance is an essential part of long-term care, as ongoing monitoring helps to identify potential complications early. Patients should discuss treatment options with their healthcare team and consider genetic counseling as part of overall management.

The outlook for individuals with Allan-Herndon-Dudley syndrome is variable, with severity and symptoms differing widely among affected individuals. With current standards of care and supportive therapies, many individuals continue to live into adulthood, although the condition remains a lifelong challenge with potential for motor and functional decline. Outcomes described in medical literature continue to evolve as standards of care improve. Families are encouraged to connect with specialists and genetic counselors for guidance, as well as to consider involvement in disease registries to help enhance understanding of the condition over time.

Clinical trials are underway exploring new treatment approaches for Allan-Herndon-Dudley syndrome. Although no targeted therapy has yet been approved, several studies are investigating novel methods to improve thyroid hormone transport and manage neurologic symptoms. Individuals interested in clinical trials are encouraged to search ClinicalTrials.gov or consult their care team about eligibility.