Vargel Ibrahim, Cil Barbaros E, Er Nuray, Ruacan Sevket, Akarsu A Nurten, Erk Yucel
Department of Plastic and Reconstructive Surgery, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
Am J Med Genet. 2002 Apr 15;109(1):22-35. doi: 10.1002/ajmg.10282.
Primary intraosseous vascular anomaly, previously called intraosseous hemangioma, is a very rare malformation that is usually seen in the vertebral column and in the skull. It is exclusively described in sporadic cases and no hereditary component has yet been reported. The most commonly affected bones in the skull are the mandible and the maxilla, and life-threatening bleeding after a simple tooth extraction is frequently observed. Here, we report two consanguineous families containing a total of four affected patients manifesting primary intraosseous vascular malformation (VMOS (vascular malformation osseous)) of the craniofacial region. The phenotypic expression is remarkably similar in both families. The characteristic findings include severe blood vessel expansions within the craniofacial bones and midline abnormalities such as diastasis recti, supraumbilical raphe, and hiatus hernia. Malformation is restricted to the mandibular and maxillary area in the prepubertal age, and rapid expansion starts after age 12 or 13. A 15-year follow-up of one of the patients demonstrated that the vascular malformation did not extend beyond the craniofacial region despite severe involvement of almost all bones in the skull. Detailed clinical and radiological evaluation provided neither evidence of soft-tissue involvement nor any sign of gross arterial, venous, or combined malformations, indicating that bone changes are a primary rather than a secondary effect due to any other vascular anomaly in the craniofacial region. An antibody against a universal proliferation marker, Ki-67, detected nonproliferative, single-layered endothelial cells, suggesting that this abnormality is a vascular malformation rather than a hemangioma. alpha-actin staining (antibody against perivascular tissue such as smooth muscle cells (SMCs) and/or pericytes) demonstrated that pathologic vessels lost their surrounding supportive tissues, as was previously seen in other types of vascular anomaly. Homozygosity mapping excluded the following loci and/or genes: multiple cutaneous venous malformation (VMCM1; gene, TIE2) on chromosome 9p21; venous malformation with glomus cells (VMGLOM) on chromosome 1p22-p21; hereditary hemorrhagic telangiectasia type 1 (HHT1; gene, endoglin) and type 2 (HHT2; gene, activin) on chromosomes 9q34.1 and 12q11-q14, respectively; and cerebral cavernous malformation type 1 (CCM1; gene, KRIT1), type 2 (CCM2), and type 3 (CCM3) on chromosomes 7q11.2-q21, 7p15-p13, and 3q35.2-q27, respectively. To the best of our knowledge, this is a new disorder, which we call hereditary intraosseous vascular malformation of the craniofacial region.
原发性骨内血管异常，以前称为骨内血管瘤，是一种非常罕见的畸形，通常见于脊柱和颅骨。仅在散发病例中有描述，尚未报道有遗传成分。颅骨中最常受累的骨骼是下颌骨和上颌骨，常观察到在简单拔牙后出现危及生命的出血。在此，我们报告两个近亲家庭，共有四名受影响患者表现为颅面部原发性骨内血管畸形（VMOS（骨内血管畸形））。两个家庭的表型表达非常相似。特征性表现包括颅面骨内严重的血管扩张和中线异常，如腹直肌分离、脐上缝、和食管裂孔疝。畸形在青春期前仅限于下颌骨和上颌骨区域，12岁或13岁后开始迅速扩展。对其中一名患者进行的15年随访表明，尽管颅骨几乎所有骨骼都严重受累，但血管畸形并未超出颅面部区域。详细的临床和放射学评估既未提供软组织受累的证据，也未发现任何粗大动脉、静脉或混合畸形的迹象，表明骨改变是颅面部区域任何其他血管异常的原发性而非继发性效应。针对通用增殖标志物Ki-67的抗体检测到非增殖性单层内皮细胞，表明这种异常是血管畸形而非血管瘤。α-肌动蛋白染色（针对血管周围组织如平滑肌细胞（SMC）和/或周细胞的抗体）表明病理性血管失去了其周围的支持组织，这与之前在其他类型血管异常中所见相同。纯合子定位排除了以下位点和/或基因：9号染色体p21上的多发性皮肤静脉畸形（VMCM1；基因，TIE2）；1号染色体p22-p21上的伴有球细胞的静脉畸形（VMGLOM）；分别位于9号染色体q34.1和12号染色体q11-q14上的遗传性出血性毛细血管扩张症1型（HHT1；基因，内皮糖蛋白）和2型（HHT2；基因，激活素）；以及分别位于7号染色体q11.2-q21、7号染色体p15-p13和3号染色体q35.2-q27上的脑海绵状畸形1型（CCM1；基因，KRIT1）、2型（CCM2）和3型（CCM3）。据我们所知，这是一种新的疾病，我们称之为颅面部遗传性骨内血管畸形。
