contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A

Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A is a condition primarily affecting the musculoskeletal system, characterized by joint contractures and distinctive facial features. Variants in the MYH3 gene, which plays a key role in muscle development, are the known biological basis of this condition. It is inherited in an autosomal dominant pattern, meaning a single altered copy can lead to the syndrome. This condition is very rare, affecting fewer than 1 in 1,000,000 people.

Clinically, the syndrome is marked by a number of characteristic musculoskeletal and craniofacial features. Almost all affected individuals present with a short neck and camptodactyly, while many also exhibit webbed neck, short stature, and ptosis. Additional findings such as hip and elbow contractures, posteriorly rotated and low-set ears, downslanted palpebral fissures, and scoliosis are reported, with some features occurring in a subset of individuals. Not all individuals experience all these features, and severity varies considerably.

The condition is caused by pathogenic variants in the MYH3 gene. MYH3 encodes a myosin protein important for normal muscle formation, and disruptions in its function are believed to contribute to the development of the musculoskeletal abnormalities seen in this syndrome. It is inherited in an autosomal dominant manner, which means that a single altered copy of the gene is sufficient for the condition to manifest, and an affected individual has a 50% chance of passing the variant to each child. Not all individuals who inherit the variant will experience all features, and the severity can vary, reflecting variable expressivity.

Currently, management focuses on supportive care and symptom management, with treatment tailored to the individual. Since there are no specific foundational therapies or FDA-approved treatments for this condition, care is centered on a multidisciplinary approach that may include physical and occupational therapy to optimize mobility and function. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Genetic counseling is recommended to help families understand inheritance patterns and discuss family planning options.

The clinical course of contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A is variable, with outcomes that can differ significantly between individuals. Some may experience relatively stable symptoms over time, while others could face progressive challenges especially related to musculoskeletal function and mobility. With current standards of care, many individuals maintain a good quality of life and benefit from advances in supportive management. Outcomes described in medical literature continue to evolve as standards of care improve, and families are encouraged to seek guidance from specialists familiar with the condition.

This condition is an active area of research with numerous ongoing clinical trials exploring new treatment approaches. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility and opportunities to participate in research.