Eeva Castrén1, Päivi Salminen2, Miikka Vikkula3, Anne Pitkäranta4, Tuomas Klockars4. 1. Department of Otorhinolaryngology and Head and Neck Surgery, Helsinki University Hospital, University of Helsinki, Helsinki, Finland; eeva.castren@helsinki.fi. 2. Department of Pediatric Surgery, Children's and Adolescent's Hospital, Helsinki University Hospital, Helsinki, Finland; and. 3. Human Molecular Genetics, de Duve Institute, Université catholique de Louvain, Brussels, Belgium. 4. Department of Otorhinolaryngology and Head and Neck Surgery, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
Abstract
BACKGROUND AND OBJECTIVE: Infantile hemangioma (IH) includes, among its other risk factors, familial clustering, but a definitive understanding of IH's inheritance model and genetic basis is lacking. Our objective was to collect IH pedigrees in Finland, to study the inheritance patterns of IH within these families, and to analyze the characteristics of familial IHs. METHODS: We identified 185 patients with IH who visited our vascular anomaly clinic between 2004 and 2007. Based on hospital records and a questionnaire sent to these patients and their families, IH characteristics and family history of IH were studied. We compared characteristics between patients with positive (familial) and negative (sporadic) IH family history. Families with positive IH family history were further interviewed for extended pedigree data. RESULTS: One-third of our IH cohort's families reported a family history positive for IH, with IH characteristics and perinatal data between the familial and sporadic cases being similar. IH patients with affected first-degree relatives reported higher long-term discomfort rates than the sporadic cases. Of the 40 families interviewed, 11 included ≥4 IH-affected family members; these were most commonly first-degree relatives (63%). Segregation patterns match with autosomal dominant inheritance with an incomplete penetrance or maternal transmission. We also present a case of monozygotic twins that manifest identical IHs. CONCLUSIONS: Based on this large number of IH pedigrees, we suggest at least 2 possible mechanisms of inheritance: autosomal dominant and maternal transmission. This study highlights the need for additional genetic studies to define inheritance of this common disease.
BACKGROUND AND OBJECTIVE: Infantile hemangioma (IH) includes, among its other risk factors, familial clustering, but a definitive understanding of IH's inheritance model and genetic basis is lacking. Our objective was to collect IH pedigrees in Finland, to study the inheritance patterns of IH within these families, and to analyze the characteristics of familial IHs. METHODS: We identified 185 patients with IH who visited our vascular anomaly clinic between 2004 and 2007. Based on hospital records and a questionnaire sent to these patients and their families, IH characteristics and family history of IH were studied. We compared characteristics between patients with positive (familial) and negative (sporadic) IH family history. Families with positive IH family history were further interviewed for extended pedigree data. RESULTS: One-third of our IH cohort's families reported a family history positive for IH, with IH characteristics and perinatal data between the familial and sporadic cases being similar. IH patients with affected first-degree relatives reported higher long-term discomfort rates than the sporadic cases. Of the 40 families interviewed, 11 included ≥4 IH-affected family members; these were most commonly first-degree relatives (63%). Segregation patterns match with autosomal dominant inheritance with an incomplete penetrance or maternal transmission. We also present a case of monozygotic twins that manifest identical IHs. CONCLUSIONS: Based on this large number of IH pedigrees, we suggest at least 2 possible mechanisms of inheritance: autosomal dominant and maternal transmission. This study highlights the need for additional genetic studies to define inheritance of this common disease.