1115 - The Need for Early Genomic Sequencing: A Pediatric Case Report of Allan-Herndon-Dudley Syndrome

Case Diagnosis: 3-year-old male with Allan-Herndon-Dudley Syndrome (AHDS)

Case Description: Patient is a 3-year-old male with a history of AHDS, global developmental delay, failure to thrive, and laryngomalacia. He has opisthotonic posturing, poor neck strength, and hypotonic extremities and is aphasic and nonambulatory. Both parents have intellectual and developmental delay of unknown cause, and a cousin has muscular dystrophy. Microarray, karyotype, fragile X, and genetic panel for developmental delay were negative. Whole genome sequencing through GeneDx XomeDx Trio was notable for pathogenic hemizygous x-linked variant in SLC16A2 gene, and he was subsequently diagnosed with AHDS. He was referred to orthopedic surgery for cervical instability and neurology for hypotonia with extensor muscle predominance. He receives speech, PT and OT for abnormal muscle tone and poor head control and has frequent family training meetings. He uses a C-spine collar for support, multiple braces to prevent contractures, and CoughAssist and vest with good effect.

Discussions: AHDS syndrome is a rare x-linked disorder with an estimated prevalence of 1 per 70,000 males. Mutations in the SLC16A2 gene cause a defect in thyroid hormone transporter, monocarboxylate transporter 8. Patients with AHDS often present with neurodevelopmental delay, muscle hypoplasia, axial hypotonia progressing to spasticity, pyramidal and extrapyramidal signs, cerebellar symptoms, and distinctive facial features. Although an exact diagnosis was not made until whole genomic sequencing, our patient eventually received rehabilitation services. Like our patient, children with neuromuscular manifestations of diseases benefit from early intervention. Early genetic screening can be beneficial for determining the cause of neuromuscular symptoms, planning appropriate multidisciplinary treatment, and rehabilitation management.

Conclusions: This is a rare case of AHDS in which whole genomic sequencing established diagnosis. Particularly given a family history of genetic abnormalities, whole genomic sequencing should be utilized early to determine potential causes of neuromuscular symptoms and to provide early rehabilitation intervention to prevent worsening of function.