Kyphoscoliotic Ehlers-Danlos Syndrome (kEDS) is a rare, inherited disorder affecting connective tissues throughout the body. Connective tissue supports and structures many body parts, including skin, bones, blood vessels, and organs. This condition is classified as one of the subtypes within the broader group of Ehlers-Danlos syndromes. Affecting fewer than 1 in 1 million people, kEDS is characterized by specific physical manifestations apparent early in life.
Understanding Kyphoscoliotic EDS
Kyphoscoliotic EDS primarily affects the musculoskeletal system, leading to distinct physical characteristics. A prominent feature is kyphoscoliosis, a combined curvature of the spine involving both a forward hunch (kyphosis) and a sideways curve (scoliosis). This spinal curvature often begins in early childhood and can progressively worsen, potentially requiring orthopedic intervention.
Individuals with kEDS also exhibit generalized joint hypermobility, where joints extend beyond the typical range of motion. This often results in unstable joints prone to frequent dislocations, particularly in areas like the shoulders, hips, and knees. Muscle hypotonia, or low muscle tone, is present from birth, causing infants to appear “floppy” and potentially delaying motor development milestones like sitting and walking.
Beyond musculoskeletal issues, kEDS impacts the skin, making it soft, stretchy, and easily bruised. The skin may also be fragile, leading to poor wound healing and widened, atrophic scars. Ocular involvement is also common, with features like scleral fragility and microcornea, a smaller-than-usual transparent front part of the eye. Some individuals may also experience osteopenia, reduced bone mass, and fragile artery walls, increasing the risk of medium-sized artery rupture.
Genetic Basis and Inheritance
Kyphoscoliotic EDS is primarily caused by specific genetic changes, most commonly in the PLOD1 gene. This gene provides instructions for producing an enzyme called lysyl hydroxylase 1. Lysyl hydroxylase 1 plays a role in the formation of collagen, a protein providing strength and flexibility to connective tissues. When the PLOD1 gene is altered, the enzyme may be faulty or insufficient, leading to weakened collagen and fragile connective tissues throughout the body.
The inheritance pattern for kEDS is autosomal recessive. This means an individual must inherit two altered gene copies—one from each parent—to develop the condition. Parents who carry one mutated PLOD1 gene copy are unaffected, as they have a functional gene to compensate. A less common cause of kEDS involves mutations in the FKBP14 gene, which is thought to affect collagen protein folding.
Diagnosis and Clinical Evaluation
Diagnosing Kyphoscoliotic EDS involves a comprehensive clinical evaluation based on characteristic signs and symptoms. Healthcare professionals look for the major criteria, including congenital muscle hypotonia, early-onset progressive kyphoscoliosis, and generalized joint hypermobility with frequent dislocations. Other features like skin hyperextensibility, easy bruising, and ocular fragility are also considered.
A definitive diagnosis of kEDS is confirmed through genetic testing, specifically sequencing of the PLOD1 gene. Beyond genetic testing, other evaluations assess the condition’s extent and guide management. Imaging studies, like X-rays or MRIs, monitor spinal curvature progression. Eye examinations check for ocular involvement.
Managing the Condition
Managing Kyphoscoliotic EDS focuses on symptomatic treatment and supportive care, as there is no cure. A multidisciplinary approach involves various specialists to address kEDS’s diverse manifestations. Physical therapy aims to maintain joint mobility, improve muscle strength, and aid motor development.
Orthopedic interventions, such as bracing or surgery, may be necessary for severe kyphoscoliosis to correct or stabilize spinal curvature. Pain management strategies alleviate discomfort from joint instability and other symptoms. Regular monitoring for complications includes eye examinations to detect and manage ocular issues, and assessments for vascular fragility. A coordinated care team, including geneticists, orthopedists, physical therapists, and ophthalmologists, provides comprehensive care tailored to individual needs.