combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1

Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1 is a complex connective tissue disorder that presents with features overlapping both osteogenesis imperfecta and Ehlers-Danlos syndrome. The condition is associated with pathogenic variants in the COL1A1 gene, which plays a crucial role in the production of type I collagen, a key structural protein in bones, skin, and other tissues. It follows an autosomal dominant inheritance pattern, meaning an affected individual has a 50% chance of passing the altered gene to their offspring. Precise prevalence estimates are not well established, and the clinical spectrum is known to vary significantly between individuals.

Individuals with combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1 typically present with several hallmark clinical features. Characteristic findings include poor wound healing, dermal translucency, hyperextensible skin, reduced bone mineral density, recurrent joint dislocation, blue sclerae, recurrent fractures, joint hypermobility, generalized hypotonia, and a susceptibility to bruising, all of which are reported as always present. In addition, some patients may experience scoliosis and short stature in most cases, while inguinal hernia, arterial rupture, and atrial septal defect occur in a subset of affected individuals. Not all individuals experience all features, and severity varies considerably, underscoring the variable expressivity of the condition.

This condition is caused by variants in the COL1A1 gene, which provides instructions for making a component of type I collagen. Disruption in the function of this protein affects the strength and integrity of connective tissues throughout the body, leading to the combined features of osteogenesis imperfecta and Ehlers-Danlos syndrome. The disorder is inherited in an autosomal dominant pattern, meaning that a single altered copy of the gene is sufficient to cause the condition, and each child of an affected individual has a 50% chance of inheriting the variant. Genetic counseling is recommended to help families understand inheritance patterns and implications for family planning.

Currently, management focuses on supportive care and symptom management because there are no FDA-approved treatments specifically linked to this condition. Treatment is tailored to the individual and typically involves a multidisciplinary team approach, emphasizing both foundational therapies and long-term surveillance. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Patients are encouraged to work with specialists knowledgeable in connective tissue disorders and to seek genetic counseling to discuss treatment options and family planning.

The long-term outlook for individuals with combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1 varies widely, reflecting the heterogeneous nature of the condition. With current standards of care and ongoing advances in multidisciplinary management, many individuals are able to manage symptoms and maintain a good quality of life into adulthood. Outcomes may differ depending on symptom severity, age at diagnosis, and access to specialized care, and the clinical course can range from periods of stability to phases where additional complications may arise. Families often find it helpful to connect with specialists experienced in managing complex connective tissue disorders, and genetic counseling can provide additional guidance regarding the variable expressivity of the condition. Outcomes described in medical literature continue to evolve as standards of care improve.