campomelic dysplasia

Campomelic dysplasia is a very rare skeletal dysplasia that affects the development of bones, airway structures, and several internal organs. Most cases are caused by changes in the SOX9 gene, which plays a critical role in cartilage formation and sexual development. Features usually become apparent before birth or in the newborn period, and the condition can affect individuals of any sex, with differences in sex development reported in many affected males. It is estimated to affect fewer than one in one million people worldwide.

The hallmark of campomelic dysplasia is abnormal bone formation that leads to bowed, fragile long bones, under-developed shoulder blades, and a characteristically narrow chest with eleven pairs of ribs instead of the usual twelve. Early signs often include a small chin, flattened midface, cleft palate, and a short neck. Respiratory distress is common in newborns because of a small, flexible airway (tracheomalacia and laryngomalacia) and limited space in the chest. As children grow, spinal problems such as cervical spine instability, cervical kyphosis, and scoliosis may emerge, and recurrent fractures can occur as bones remain brittle. Two-thirds of affected boys have hypospadias or more extensive sex reversal, reflecting the role of SOX9 in sex development. Less common or variable findings include hip dislocation, macrocephaly, and kidney or heart malformations. Not all individuals experience every feature, and severity varies considerably between people with the same diagnosis.

Campomelic dysplasia is usually caused by pathogenic variants in the SOX9 gene. SOX9 provides instructions for making a transcription factor that guides cartilage formation, bone growth, and aspects of sex determination before birth. The condition is inherited in an autosomal dominant pattern, meaning a change in one copy of SOX9 is enough to cause disease and each child of an affected individual has a 50 percent chance of inheriting the variant. Even within the same family, the exact symptoms and their severity can vary markedly (variable expressivity). Because of this variability and the significant implications for family planning, genetic counseling is strongly recommended for affected individuals and their relatives.

Currently, management focuses on supportive care and symptom management. Immediate priorities often include securing the airway, providing respiratory support, and stabilizing fragile bones. Orthopedic interventions may address spinal instability or severe limb bowing, while surgical repair of cleft palate or hypospadias can improve feeding, speech, and urinary function. Long-term care relies on a multidisciplinary team—typically including neonatologists, pulmonologists, orthopedic surgeons, otolaryngologists, and physical therapists—to coordinate individualized treatment plans. Regular surveillance is an essential part of long-term care, helping to identify potential complications such as progressive scoliosis, airway obstruction, or recurrent fractures before they become serious. Families should discuss available interventions and monitoring schedules with specialists experienced in skeletal dysplasias, and genetic counseling can guide future family planning decisions.

Outcomes for people with campomelic dysplasia range from life-threatening respiratory problems in infancy to survival into childhood or adulthood with ongoing orthopedic and respiratory challenges. Severity and symptoms vary widely between individuals, even when the same genetic variant is present. Respiratory stability, cervical spine integrity, and the degree of chest narrowing are key factors influencing long-term health. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with multidisciplinary teams familiar with this condition, and genetic counseling can provide guidance on inheritance and support resources.