Calvarial doughnut lesions with bone fragility in a French-Canadian family; case report and review of the literature
Shuaa Basalom,
Mélissa Fiscaletti,
Valancy Miranda,
Céline Huber,
Guillaume Couture,
Régen Drouin,
Élise Monceau,
Sandrine Wavrant,
Johanne Dubé,
Outi Mäkitie,
Valérie Cormier-Daire,
Philippe M. Campeau
Affiliations
Shuaa Basalom
Division of Medical Genetics, Department of Specialized Medicine, McGill University Health Center, Montreal, QC H4A 3J1, Canada
Mélissa Fiscaletti
Department of Pediatrics, CHU Sainte-Justine, Montreal, QC H3T 1C5, Canada
Valancy Miranda
Medical Genetics Division, Department of Pediatrics, CHU Sainte-Justine, Montreal, QC H3T 1C5, Canada
Céline Huber
Department of Medical Genetics, INSERM UMR 1163, Paris Descartes-Sorbonne Paris Cité University, IMAGINE Institute, Necker Enfants Malades Hospital, Paris, France
Guillaume Couture
Centre de rhumatologie, CHU Purpan, 31300 Toulouse, France
Régen Drouin
Division of Medical Genetics, Department of Pediatrics, CHU de Quebec – ULaval, Faculty of Medicine, Université Laval, Quebec City, Canada
Élise Monceau
Department of Pediatrics, CHU Sainte-Justine, Montreal, QC H3T 1C5, Canada
Sandrine Wavrant
Department of Obstetrics and Gynecology, CHU Sainte-Justine, Montreal, QC H3T 1C5, Canada
Johanne Dubé
Department of Obstetrics and Gynecology, CHU Sainte-Justine, Montreal, QC H3T 1C5, Canada
Outi Mäkitie
Children's Hospital and Pediatric Research Center, University of Helsinki and Helsinki University Hospital, FI-00014 Helsinki, Finland
Valérie Cormier-Daire
Centre de référence MOC, hôpital Necker, 75015 Paris, France; Corresponding authors.
Philippe M. Campeau
Medical Genetics Division, Department of Pediatrics, CHU Sainte-Justine, Montreal, QC H3T 1C5, Canada; Corresponding authors.
Calvarial Doughnut Lesions with Bone Fragility (CDL) is an autosomal dominant genetic disease, characterized by low bone mineral density, multiple fractures starting in childhood, and sclerotic doughnut-shaped lesions in the cranial bones. Aubé and colleagues described in 1988 a French-Canadian family of 12 affected members who had a clinical diagnosis of doughnut lesions of the skull, with pathological fractures, osteopenia, “bone in bone” in the vertebral bodies and squaring of metatarsal and metacarpal bones. Herein we study new members of this family. Sequential genetic testing identified a nonsense variant c.148C>T, p. Arg50⁎ in SGMS2 previously reported in other families. SGMS2 encodes Sphingomyelin Synthase 2, which produces Sphingomyelin (SM), a major lipid component of the plasma membrane that plays a role in bone mineralization. The nonsense variant is associated with milder phenotype. The proband presents with bone in bone vertebral appearance that had been defined uniquely in the first cases described in the same family. The proband's son was identified to carry the same variant, which makes him the sixth generation with the diagnosis of CDL. We also report that the same pathogenic variant was identified in another previously described family, from France. These reports further confirm the genetic basis of CDL, the recurrence of the same variant (p.Arg50*) in individuals of the same ancestry, and the variable penetrance of some of the clinical findings.
