How do connective tissue disorders, such as Ehlers-Danlos syndrome (EDS) or Marfan syndrome (MS), affect hip development in pediatric and adolescent patients, potentially leading to pathological asymmetry in adulthood?

Connective Tissue Disorders and Hip Asymmetry Development

Connective tissue disorders cause pathological hip asymmetry through abnormal collagen and connective tissue that leads to joint instability, recurrent subluxations/dislocations, and asymmetric mechanical loading during critical growth periods, with the most severe manifestation being congenital bilateral hip dislocation in arthrochalasia Ehlers-Danlos syndrome. 1

Primary Mechanisms of Hip Asymmetry

Joint Hypermobility and Instability

• Joint hypermobility is the fundamental driver, with EDS patients showing altered collagen fibril structure that triggers fibroblast dysfunction and abnormal connective tissue adhesion 2
• The hip joint is particularly vulnerable, with 92% of pediatric EDS patients demonstrating hypermobility at the knees and similar rates at other joints, creating a systemic pattern of instability 3
• Recurrent subluxations and dislocations occur in 10% of children with joint hypermobility syndrome, with actual hip dislocations documented in 4% 3

Congenital Hip Dislocation

• Arthrochalasia EDS presents with congenital bilateral hip dislocations as a defining feature, caused by mutations leading to loss of exon 6 in COL1A1 or COL1A2 genes 1
• In classic EDS, congenital hip dislocation occurs but is often diagnosed late—at 6 months in some cases but frequently not until 2-5 years of age, allowing asymmetric development to progress 4
• "Clicky" hips at birth occur in 12% of children with joint hypermobility-related conditions, representing early instability that can progress to asymmetry 3

Asymmetric Loading and Compensatory Patterns

• Delayed motor development compounds the problem: mean age at first walking is 15 months (versus 12-14 months typically), with 48% considered "clumsy" and 36% having poor coordination 3
• Abnormal gait occurs as a presenting complaint in 10% of cases, indicating that compensatory movement patterns develop early and become entrenched during critical growth phases 3
• Limitation of hip abduction—the most important clinical finding in hip dysplasia after 2-3 months of age—develops asymmetrically when one hip is more unstable than the other 5

Progressive Pathological Changes

Childhood Through Adolescence

• The average delay from symptom onset to diagnosis is 2-3 years (symptoms begin at mean age 6.2 years, diagnosis at 9.0 years), during which abnormal biomechanics continue unchecked 3
• Recurrent joint sprains occur in 20% of patients, with the knee being most commonly affected (43.4% presenting complaint), but back (32.2%) and shoulder (31.2%) involvement indicates systemic instability that affects the pelvis and hip girdle 6
• Scoliosis and spinal asymmetry are common diagnoses, creating secondary pelvic obliquity that further drives hip asymmetry 6

Specific Marfan Syndrome Considerations

• Congenital contractures of hips occur in Congenital Contractural Arachnodactyly (CCA/Beals syndrome), a Marfan-related condition, which can improve with physical therapy but establishes early asymmetric patterns 7
• Protrusio acetabuli (scored as 2 points in the systemic features scoring system) represents progressive medial migration of the acetabulum, which can occur asymmetrically 7
• Marfan patients have mutations in fibrillin-1 gene affecting extracellular matrix microfibrils, leading to loss of elastic fibers and cystic medial anomalies in connective tissues including joint capsules 7

Clinical Pitfalls and Recognition

Diagnostic Delays

• Only 10% of referrals recognize hypermobility as the cause of joint complaints, leading to prolonged periods of abnormal loading 3
• Early cases may be misdiagnosed as arthrogryposis multiplex congenita, Larsen's syndrome, or Marfan syndrome, with the characteristic EDS triad not appearing until 4-6 years of age 8
• The absence of limb length discrepancy early on does not exclude developing asymmetry—shortening develops progressively with chronic subluxation and altered growth plate loading 5, 9

Functional Impact

• 67% of children with joint hypermobility syndrome have major limitations in physical activities, and 41% miss significant schooling, indicating that compensatory patterns become deeply ingrained 3
• By adulthood in arthrochalasia EDS, 4 of 12 patients (33%) become wheelchair-bound or unable to walk unaided, representing the end-stage of progressive asymmetric degeneration 1

Genotype-Phenotype Relationships

Individuals with arthrochalasia EDS due to COL1A1 variants causing complete or partial loss of exon 6 are more severely affected regarding musculoskeletal features compared to COL1A2 variants 1. This suggests that the specific molecular defect determines the severity of hip involvement and asymmetry development.

Vascular EDS (type IV) involves COL3A1 mutations affecting type III collagen, with mutations widely distributed throughout the gene and no clustering patterns, making prediction of specific joint involvement difficult 2. However, this type poses the greatest risk due to arterial complications rather than hip asymmetry 2.

Management Implications

• Hip surgery was required in 5 of 12 patients with arthrochalasia EDS, with a total of 42 procedures needed across 8 patients due to difficulties in achieving and maintaining reduction 1, 4
• Both femoral and innominate osteotomies are necessary to achieve stable reduction in EDS patients with congenital hip dislocation 4
• Avascular necrosis of the femoral head developed in 5 hips among EDS patients treated for hip dislocation, with 4 occurring after closed reduction under general anesthesia, highlighting the fragility of these tissues 4