Porayette Prashob, Fruitman Deborah, Lauzon Julie L, Le Goff Carine, Cormier-Daire Valérie, Sanders Stephen P, Pinto-Rojas Alfredo, Perez-Atayde Antonio R
1 Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Pediatr Dev Pathol. 2014 May-Jun;17(3):209-16. doi: 10.2350/13-08-1370-CR.1. Epub 2013 Nov 19.
Geleophysic dysplasia (GD) is a rare genetic disorder characterized by acromelic dysplasia. Geleophysic dysplasia type 1 (MIM 231050) is autosomal recessive and is caused by homozygous or compound heterozygous mutation in the ADAMTSL2 (a disintegrin and metalloproteinase with thrombosponding repeats-like 2) gene. Geleophysic dysplasia type 2 (MIM 614185) is autosomal dominant and is caused by heterozygous mutation in the fibrillin 1 (FBN1) gene. Here, we present the clinical and histopathologic findings in a child with GD with newly identified ADAMTSL2 mutations. The 1st mutation was probably a pathogenic one, c.[1934G>A] p.[Arg645His], located in exon 13; the 2nd, in intron 8, was probably changing a splice site. While the light and electron microscopic findings were similar to those previously described, hydrocephalus due to aqueductal stenosis might be a new associated finding in these patients. This child with these 2 novel mutations also had an aggressive clinical course with early-onset progressive cardiac valvular disease.
脂肪代谢障碍性发育异常（GD）是一种罕见的遗传性疾病，其特征为肢端发育异常。1型脂肪代谢障碍性发育异常（MIM 231050）为常染色体隐性遗传，由ADAMTSL2（含血小板反应蛋白基序的解聚素样金属蛋白酶2）基因的纯合或复合杂合突变引起。2型脂肪代谢障碍性发育异常（MIM 614185）为常染色体显性遗传，由原纤蛋白1（FBN1）基因的杂合突变引起。在此，我们报告了一名患有GD且新发现ADAMTSL2突变的儿童的临床和组织病理学检查结果。第一个突变可能是致病性的，即位于第13外显子的c.[1934G>A] p.[Arg645His]；第二个位于第8内含子，可能改变了一个剪接位点。虽然光镜和电镜检查结果与之前描述的相似，但导水管狭窄导致的脑积水可能是这些患者新出现的相关表现。这名具有这两种新突变的儿童还经历了侵袭性的临床病程，伴有早发性进行性心脏瓣膜病。
