Bostwick Bret, Fang Ping, Patel Ankita, Sutton V Reid
Am J Med Genet C Semin Med Genet. 2016 Mar;172C(1):9-20. doi: 10.1002/ajmg.c.31473. Epub 2016 Feb 7.
Focal dermal hypoplasia, or Goltz syndrome, is a highly variable X-linked dominant disorder with abnormalities in ectoderm and mesoderm derived tissues. Classic clinical features include patchy hypoplastic skin, split hand/foot deformities, and ocular malformations. We aimed to refine the understanding of the phenotypic spectrum and natural history of this disorder and now present multi-disciplinary clinical description and medical history review for 18 patients with focal dermal hypoplasia. All disease characteristics were analyzed and compiled in aggregate to aid in development of clinical diagnostic criteria. Medical history data unexpectedly revealed that the majority of patients (87%) had undergone tonsillectomy for obstructive sleep apnea, which exposed an important co-morbidity that is not well described in the literature, but managing physicians should be made aware of. Fifteen of the 18 patients underwent molecular sequencing of PORCN to detect heterozygous or mosaic mutations. Where no mutation was detected, we performed exon-targeted chromosomal microarray to evaluate for large deletions of the PORCN gene region. We detected a pathogenic genotype in 14 of 15 patients, including one novel chromosomal deletion and four novel PORCN sequence variants. Here, we provide phenotypic summary analysis of 18 patients with focal dermal hypoplasia and propose clinical diagnostic criteria.
局灶性真皮发育不全，即戈尔茨综合征，是一种高度可变的X连锁显性疾病，外胚层和中胚层来源的组织存在异常。典型的临床特征包括斑片状皮肤发育不全、手足裂畸形和眼部畸形。我们旨在加深对该疾病表型谱和自然史的理解，现呈现18例局灶性真皮发育不全患者的多学科临床描述和病史回顾。对所有疾病特征进行汇总分析，以协助制定临床诊断标准。病史数据意外显示，大多数患者（87%）因阻塞性睡眠呼吸暂停接受了扁桃体切除术，这揭示了一种文献中未充分描述的重要合并症，但应让主治医生知晓。18例患者中有15例接受了PORCN基因的分子测序，以检测杂合或嵌合突变。若未检测到突变，我们进行外显子靶向染色体微阵列检测，以评估PORCN基因区域的大片段缺失。我们在15例患者中的14例检测到致病基因型，包括1例新的染色体缺失和4例新的PORCN序列变异。在此，我们提供18例局灶性真皮发育不全患者的表型汇总分析，并提出临床诊断标准。
