Osteochondritis Dissecans Lesions in Family Members: Does a Positive Family History Impact Phenotypic Potency?

Although repetitive microtrauma and athletic overuse patterns are most commonly associated with osteochondritis dissecans (OCD), recent studies have identified a potential genetic predisposition for OCD. Several case series have documented family pedigrees that support autosomal-dominant inheritance, but the families in these studies were all selected as a result of unique histories that may not accurately represent OCD inheritance patterns at large. Because there has been little investigation beyond these case reports, we aimed to describe a broader, more representative pattern of OCD inheritance applicable to all affected patients.

(1) What proportion of patients treated for OCD of the knee have one or more immediate and/or extended family members with a history of OCD lesions? (2) Do patients with more phenotypically potent lesions, which we defined as patients with bilateral OCD lesions or patients who have undergone multiple procedures for OCD, have a higher frequency of affected relatives than those with less potent lesions?

This retrospective study queried patient databases, diagnosis codes (International Classification of Diseases, 9th Revision), and surgical logs at a regional, tertiary care children’s hospital to identify all patients treated over a 10-year period (March 2004–March 2014) by the senior author for OCD of the knee. All patients aged 0–18 years at the time of diagnosis were included. At our institution, patients with intact lesions are treated with a trial of conservative therapy; conversely, patients with a break in the articular cartilage and/or loose fragments of bone/cartilage are treated surgically. There were no OCD-specific contraindications to surgery. This search identified 543 patients. After patient identification, a questionnaire was designed that asked for the number, age, and gender of all immediate family members and the history of OCD lesions in any family member (immediate or extended). For all positive family members, patients were further queried regarding relevant clinical details to affirm a history of OCD. Patients were contacted by mailed questionnaires and phone calls for survey completion. All 543 patients received the survey, of which 103 (19%) responded to it and were included here. Responders were approximately 1 year younger than nonresponders; there was no difference in gender distribution. A retrospective chart review was then conducted to collect demographic information, phenotypic disease severity, and treatment details. Of the 103 included patients, 20 patients (19%) with unilateral lesions were managed nonoperatively (“conservative” group), 50 patients (49%) had unilateral lesions advanced to surgery (“unilateral” group), 21 patients (20%) had bilateral lesions managed either conservatively or surgically (“bilateral” group), and 12 patients (12%) underwent multiple procedures for the same lesion (“multiple” group). Of those included, 75 patients (73%) were treated surgically. With the numbers available, there were no baseline differences among the groups in terms of gender, lesion laterality, lesion location, or number of secondary procedures at the time of the initial surgical intervention.

In total, 14 of 103 (14%) patients treated for OCD in this study had an immediate and/or extended family member with a history of OCD lesions. This included four of 20 (20%) patients in the conservative group, five of 50 (10%) in the unilateral group, four of 21 (19%) in the bilateral group, and one of 12 (8%) in the multiple group. With the numbers available, we did not identify a higher proportion of immediate and/or extended family members with a positive history of OCD in those patients with phenotypically potent lesions (bilateral and multiple) as compared with those with patients phenotypically less potent lesions (conservative and unilateral; five of 33 [15%] versus nine of 70 [13%]; odds ratio, 1.2; 95% confidence interval, 0.4–3.9; p = 0.751).

In this broad, heterogeneous cohort of pediatric patients with OCD, the proportion of patients with a positive family history of OCD was 14%, which appeared to be much higher than the reported prevalence of OCD in the general population according to prior research. Therefore, our data provide preliminary support for a familial inheritance pattern for OCD, suggesting that further clinical, biologic, and genomic investigation might help to improve our understanding of who is at highest risk for OCD and what moderating factors might influence their disease severity and risk of progression. Furthermore, our data suggest that expanded patient education and screening regarding inheritance patterns might enhance identification of potential familial disease burden and improve access to timely and appropriate treatment.

Level IV, prognostic study.