Legg-Calvé-Perthes Disease: Genetic Component
Legg-Calvé-Perthes disease (LCPD) has a confirmed genetic component, with mutations in the COL2A1 gene (encoding type II collagen) identified in familial cases, though most cases remain sporadic with multifactorial etiology including genetic predisposition. 1, 2
Genetic Evidence
Confirmed Genetic Mutations
- A recurrent missense mutation (p.G1170S) in the COL2A1 gene has been identified in a Japanese family with autosomal dominant LCPD, demonstrating considerable intra-familial phenotypic variation 1
- This represents the first confirmed mutation in hereditary LCPD, suggesting COL2A1 mutations may be more common than previously recognized, particularly in familial and/or bilateral cases 1
- COL2A1 variants are also responsible for type 1 Stickler syndrome, which presents with hip dysplasia that may be clinically indistinguishable from isolated LCPD 2
Genetic Heritability
- Twin studies demonstrate significant genetic contribution to knee osteoarthritis (a related condition) with heritability estimates of 0.39-0.65, independent of environmental or demographic confounders 3
- Family history of joint disorders is recognized as a risk factor for osteoarthritis development 3
Critical Clinical Distinction: LCPD vs. Stickler Syndrome
A case series of 19 patients with genetically confirmed type 1 Stickler syndrome were historically misdiagnosed with isolated LCPD 2
Why This Matters for Morbidity
- Children with type 1 Stickler syndrome have a very high risk of childhood blindness from giant retinal tear detachment 2
- This blindness is largely preventable if timely diagnosis is made 2
- The two conditions may be indistinguishable using current clinical diagnostic techniques alone 2
Red Flags Suggesting Stickler Syndrome (Not Isolated LCPD)
- Bilateral hip involvement 1
- Family history of hip dysplasia, retinal detachment, deafness, or cleft palate 2
- Characteristic facial features 2
- Bifid uvula or cleft palate 2
Management Implications of Genetic Component
When to Consider Genetic Testing
- Familial cases with multiple affected members 1
- Bilateral LCPD presentation 1
- Any features suggestive of Stickler syndrome (to prevent blindness) 2
- Autosomal dominant inheritance pattern in family history 1
Genetic Counseling Considerations
- If COL2A1 mutation confirmed, first-degree family members should undergo dilated eye examination to exclude retinal pathology 2
- Genetic testing should include COL2A1 sequencing in suspected familial cases 1
- Parental testing may be required to verify mutations arise in trans if compound heterozygous variants identified 3
Treatment Outcomes (Independent of Genetic Status)
The largest prospective multicenter study (345 hips in 337 patients) demonstrated that lateral pillar classification and age at onset are the strongest prognostic factors, not genetic status 4
Age-Based Treatment Algorithm
- Children ≤8 years at onset with lateral pillar B hips: Nonoperative and operative treatment yield equally favorable outcomes 4
- Children >8 years at onset with lateral pillar B or B/C border hips: Surgical treatment (femoral or innominate osteotomy) produces significantly better outcomes than nonoperative treatment (p ≤ 0.05) 4
- Lateral pillar C hips at any age: Poor outcomes regardless of treatment approach 4
Nonoperative Protocol
A 25-year experience with 240 hips demonstrated that restoration and maintenance of hip range of motion with adductor tenotomy, abduction casting, daily range-of-motion exercises, and A-frame orthosis resulted in 78% of pillar B and C hips achieving spherical congruence at maturity 5
Common Pitfalls
- Failing to screen for Stickler syndrome in children presenting with LCPD, missing opportunity to prevent blindness 2
- Assuming all LCPD is sporadic without obtaining detailed family history of hip, eye, hearing, or palate abnormalities 1, 2
- Not recognizing that COL2A1 mutations may present with variable phenotypes within the same family 1
- Overlooking bilateral presentation as a red flag for genetic etiology 1