Early diagnosis of fibrodysplasia ossificans progressiva
Early diagnosis of fibrodysplasia ossificans progressiva
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DOI：
10.1542/peds.2007-1980
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发表时间：
2008-05-01
期刊：
影响因子：
8
通讯作者：
Shore, Eileen M.
中科院分区：
文献类型：
--
作者：
Kaplan, Frederick S.;Xu, Meiqi;Shore, Eileen M.
背景。纤维浮肿骨processentiva是一种罕见且残疾的遗传状况，其特征是大脚趾的先天性畸形和特定解剖模式中的渐进性异位骨化。大多数患有纤维增生性浮肿的患者在出现异位骨化和接受可能导致终身残疾的诊断程序之前，生命早期会误诊。最近，鉴定出纤维状发育异常的遗传原因，并且在出现异性骨化之前，现在可以使用纤维状发育异常的确定性基因检测。最近，我们评估了7名儿童在异位骨化发作之前诊断出纤维状发育异常的骨骼促进症。所有患者均获得了病史，体格检查和骨骼检查，以及针对典型的纤维肿瘤肿瘤浮肿的临床基因检测。所有的7个儿童（4个女孩和3个男孩； 3个月至6岁）的先天性畸形，但在评估时，没有一个有射线照相证据表明异位骨化。这7个儿童中有5个患有颈部和背部的软组织病变，暗示着早期的纤维浮肿，骨骼促进症，其中3个经历了侵入性诊断程序，加剧了他们的病情。两个孩子没有病史或软组织肿胀或爆发的迹象。 DNA序列分析发现，所有7名儿童在甘氨酸链链菌丝菌206上具有复发性的纤维浮游生物渗透性突变，这是一种骨形蛋白质类型的激活素受体IA的单个核苷酸取代（c.617g> a）。 1受体。结论。根据畸形的大脚趾，临床怀疑是纤维肿瘤的纤维肿瘤，在生命的早期，可能会导致早期临床诊断，确认性诊断基因检测以及避免额外的有害诊断和治疗程序。这是在出现异位骨化之前的纤维肿瘤发育不全纤维增生性促进症的遗传确认的第一个报道。儿科医生应意识到纤维浮肿的早期诊断特征，甚至在出现异位骨化之前。这种意识应促使早期的遗传咨询和测试以及制定敏锐的预防措施以防止医源性伤害。
BACKGROUND. Fibrodysplasia ossificans progressiva is a rare and disabling genetic condition characterized by congenital malformation of the great toes and by progressive heterotopic ossification in specific anatomic patterns. Most patients with fibrodysplasia ossificans progressiva are misdiagnosed early in life before the appearance of heterotopic ossification and undergo diagnostic procedures that can cause lifelong disability. Recently, the genetic cause of fibrodysplasia ossificans progressiva was identified, and definitive genetic testing for fibrodysplasia ossificans progressiva is now available before the appearance of heterotopic ossification.METHODS. We recently evaluated 7 children for diagnosis of fibrodysplasia ossificans progressiva before the onset of heterotopic ossification. A medical history, physical examination, and skeletal survey were obtained on all of the patients, as well as clinical genetic testing for the canonical fibrodysplasia ossificans progressiva mutation.RESULTS. All 7 of the children (4 girls and 3 boys; ages 3 months to 6 years) had congenital malformations of the great toes, but none had radiographic evidence of heterotopic ossification at the time of evaluation. Five of the 7 children had soft tissue lesions of the neck and back, suggestive of early fibrodysplasia ossificans progressiva flare-ups, 3 of whom had undergone invasive diagnostic procedures that exacerbated their condition. Two children had no history or signs of soft tissue swelling or flare-ups. DNA sequence analysis found that all 7 of the children had the recurrent fibrodysplasia ossificans progressiva missense mutation, a single nucleotide substitution (c.617G > A) at codon 206 in the glycine-serine activation domain of activin receptor IA, a bone morphogenetic protein type 1 receptor.CONCLUSION. Clinical suspicion of fibrodysplasia ossificans progressiva early in life on the basis of malformed great toes can lead to early clinical diagnosis, confirmatory diagnostic genetic testing, and the avoidance of additional harmful diagnostic and treatment procedures. This is the first report of genetic confirmation of fibrodysplasia ossificans progressiva before the appearance of heterotopic ossification. Pediatricians should be aware of the early diagnostic features of fibrodysplasia ossificans progressiva, even before the appearance of heterotopic ossification. This awareness should prompt early genetic consultation and testing and the institution of assiduous precautions to prevent iatrogenic harm.