cataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndrome

Cataract-growth hormone deficiency-sensory neuropathy-sensorineural hearing loss-skeletal dysplasia syndrome is a complex, multi-system disorder that affects the eyes, growth, nerves, hearing, and skeletal development. It is caused by pathogenic variants in the IARS2 gene and follows an autosomal recessive inheritance pattern. The condition is extremely rare, affecting fewer than one in a million people, and generally presents in early childhood with a distinctive set of clinical findings. Modern management through a multidisciplinary care approach continues to evolve as outcomes improve over time.

Individuals with this syndrome consistently exhibit a characteristic constellation of features. Craniofacial findings include a thin vermilion border, a depressed nasal bridge, an infra-orbital crease, a short nose, and micrognathia. Skeletal abnormalities such as coronal cleft vertebrae, delayed epiphyseal ossification, short stature, a short thorax, hip dislocation, and flared metaphyses are always present. Ocular findings include cataracts, nystagmus, and hypermetropia, while sensorineural hearing loss and distal sensory impairment along with peripheral neuropathy are notable. Additional features include decreased response to growth hormone stimulation, growth delay, hypotonia, joint hypermobility, telangiectasia of the skin, hydrocephalus, motor delay, and pain insensitivity. Not all individuals experience every feature, and severity varies considerably.

This syndrome is caused by pathogenic variants in the IARS2 gene, which encodes an enzyme essential for protein synthesis in mitochondria. The disruption of this gene’s normal function leads to the multiple clinical manifestations observed in affected individuals. The condition is inherited in an autosomal recessive pattern, meaning that an affected individual has received one altered copy of IARS2 from each parent. It is more common when parents share a common ancestor, and genetic counseling is recommended to discuss recurrence risk and family planning.

Currently, management focuses on supportive care and symptom management because there are no FDA-approved treatments available for this syndrome. Treatment is tailored to the individual and typically involves a multidisciplinary team of specialists such as endocrinologists, ophthalmologists, neurologists, and orthopedists. Regular surveillance is an essential part of long-term care, helping to detect potential complications early and guide ongoing management. Genetic counseling is also recommended to help families understand the inheritance pattern and make informed decisions about family planning.

Outcomes in this syndrome are highly variable, with the clinical course ranging from stabilization after early childhood presentation to later evolving challenges. While affected individuals may experience difficulties related to growth, vision, hearing, and motor development, many benefit from ongoing multidisciplinary management. With current standards of care and regular monitoring, quality of life can be optimized, and modern interventions continue to improve long-term outcomes. Families are encouraged to connect with specialists and support resources as part of their ongoing care.