Department of Clinical Genetics, Oulu University Hospital, University of Oulu, Oulu, Finland.
Am J Med Genet A. 2009 Nov;149A(11):2371-7. doi: 10.1002/ajmg.a.33040.
Familial calvarial doughnut lesions (CDLs; OMIM 126550) is a rare autosomal dominant low bone density disorder characterized by distinctive X-ray translucencies of the skull, multiple fractures, elevated serum alkaline phosphatase, and dental caries. Only three families comprising 22 cases and 29 sporadic cases with the disorder have been reported. We describe a three-generation family consisting of three cases with clinical, radiological, biochemical, and histological findings consistent with this condition. All affected family members presented with childhood onset primary osteoporosis and typical CDLs or hyperostosis of the skull. In addition, the youngest family member was diagnosed with congenital glaucoma and her paternal grandmother with chronic congestive glaucoma. Glaucoma has not been previously described in this disorder. Adult patients also had recurrent cranial nerve palsies. No pathogenic mutations in the genes encoding low density lipoprotein receptor-related protein 5 (LRP5) or type I collagen (COL1A1 or COL1A2) were identified, suggesting that the disorder is caused by another dominant, yet unidentified gene. The literature is reviewed.
家族性颅骨环形缺损（CDL；OMIM 126550）是一种罕见的常染色体显性低骨密度疾病，其特征为颅骨有明显的 X 射线透光性、多发性骨折、血清碱性磷酸酶升高和龋齿。仅有三个家族共 22 例和 29 例散发性病例报道过这种疾病。我们描述了一个三代家族，其中有三个病例具有与该疾病一致的临床表现、影像学、生化和组织学发现。所有受影响的家族成员均表现为儿童期起病的原发性骨质疏松症和典型的颅骨 CDL 或骨过度增生。此外，最年轻的家族成员被诊断为先天性青光眼，而她的祖母患有慢性充血性青光眼。这种疾病以前没有报道过青光眼。成年患者也有复发性颅神经麻痹。在编码低密度脂蛋白受体相关蛋白 5（LRP5）或 I 型胶原（COL1A1 或 COL1A2）的基因中未发现致病性突变，提示该疾病是由另一个显性但尚未确定的基因引起的。我们对文献进行了回顾。
