Azimi Cyrus, Kennedy Shelley J, Chitayat David, Chakraborty Pranesh, Clarke Joe T R, Forrest Christopher, Teebi Ahmad S
Division of Clinical & Metabolic Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada.
Am J Med Genet A. 2003 Mar 1;117A(2):127-35. doi: 10.1002/ajmg.a.10021.
We reviewed 25 patients ascertained through the finding of trigonocephaly/metopic synostosis as a prominent manifestation. In 16 patients, trigonocephaly/metopic synostosis was the only significant finding (64%); 2 patients had metopic/sagittal synostosis (8%) and in 7 patients the trigonocephaly was part of a syndrome (28%). Among the nonsyndromic cases, 12 were males and 6 were females and the sex ratio was 2 M:1 F. Only one patient with isolated trigonocephaly had an affected parent (5.6%). All nonsyndromic patients had normal psychomotor development. In 2 patients with isolated metopic/sagittal synostosis, FGFR2 and FGFR3 mutations were studied and none were detected. Among the syndromic cases, two had Jacobsen syndrome associated with deletion of chromosome 11q 23 (28.5%). Of the remaining five syndromic cases, different conditions were found including Say-Meyer syndrome, multiple congenital anomalies and bilateral retinoblastoma with no detectable deletion in chromosome 13q14.2 by G-banding chromosomal analysis and FISH, I-cell disease, a new acrocraniofacial dysostosis syndrome, and Opitz C trigonocephaly syndrome. The last two patients were studied for cryptic chromosomal rearrangements, with SKY and subtelomeric FISH probes. Also FGFR2 and FGFR3 mutations were studied in two syndromic cases, but none were found. This study demonstrates that the majority of cases with nonsyndromic trigonocephaly are sporadic and benign, apart from the associated cosmetic implications. Syndromic trigonocephaly cases are causally heterogeneous and associated with chromosomal as well as single gene disorders. An investigation to delineate the underlying cause of trigonocephaly is indicated because of its important implications on medical management for the patient and the reproductive plans for the family.
我们回顾了25例以三角头畸形/额缝早闭为显著表现确诊的患者。16例患者中，三角头畸形/额缝早闭是唯一的显著发现（64%）；2例患者有额缝/矢状缝早闭（8%），7例患者的三角头畸形是综合征的一部分（28%）。在非综合征病例中，男性12例，女性6例，性别比为2男:1女。仅1例孤立性三角头畸形患者有患病父母（5.6%）。所有非综合征患者的精神运动发育均正常。对2例孤立性额缝/矢状缝早闭患者进行了FGFR2和FGFR3突变研究，未检测到突变。在综合征病例中，2例患有与11q 23染色体缺失相关的雅各布森综合征（28.5%）。其余5例综合征病例中，发现了不同情况，包括赛-迈耶综合征、多发先天性畸形和双侧视网膜母细胞瘤，经G显带染色体分析和荧光原位杂交在13q14.2染色体上未检测到缺失、I细胞病、一种新的肢颅骨面发育不全综合征和奥皮茨C型三角头畸形综合征。对最后2例患者用光谱核型分析和亚端粒荧光原位杂交探针研究了隐匿性染色体重排。还对2例综合征病例进行了FGFR2和FGFR3突变研究，但未发现突变。本研究表明，除了相关的美容问题外，大多数非综合征性三角头畸形病例是散发且良性的。综合征性三角头畸形病例病因异质性，与染色体以及单基因疾病相关。鉴于三角头畸形对患者医疗管理和家庭生育计划有重要影响，因此有必要进行调查以明确其潜在病因。
