Hereditary intraosseous vascular malformation of the craniofacial region: An apparently novel disorder


Vargel I., Cil B., Er N., Ruacan S., Akarsu A. N. , Erk Y.

AMERICAN JOURNAL OF MEDICAL GENETICS, cilt.109, ss.22-35, 2002 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 109 Konu: 1
  • Basım Tarihi: 2002
  • Doi Numarası: 10.1002/ajmg.10282
  • Dergi Adı: AMERICAN JOURNAL OF MEDICAL GENETICS
  • Sayfa Sayıları: ss.22-35

Özet

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 lp22-p21; hereditary hemorrhagic telangiectasia type I (HHT1; gene, endoglin) and type 2 (HHT2; gene, activin) on chromosomes 9q34.1 and 12q11-q14, respectively; and cerebral cavernous malformation type I (CCM1; gene, KRIT1), type 2 (CCM2), and type 3 (CCM3) on chromosomes 7q11.2q21, 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. (C) 2002 Wiley-Liss. Inc.