背景:Fontaineprogeroid综合征(FPS,OMIM612289)是一种最近发现的遗传性疾病,源于SLC25A24基因的致病变异,编码线粒体载体蛋白。它包括Gorlin-Chaudry-Moss综合征和Fontaine-Farriaux综合征,主要表现为颅骨融合伴短头畸形,独特的畸形面部特征,多毛症,严重的产前和产后生长受限,肢体缩短,和具有特征性皮肤变化的早期衰老,指骨异常,生殖器畸形.
方法:所有已知的FPS发生都是在产后观察到的。这里,我们介绍了在妊娠中期发现的前两个产前病例。在确认产前病例中存在大多数产后异常的同时,我们注意到在年轻胎儿中没有早衰的外观。值得注意的是,我们的报告引入了新的表型特征,如脑膨出和肾肿大,以前是出生后看不见的。此外,1例检测到父系SLC25A24镶嵌。
结论:我们介绍了FPS的最初两个胎儿实例,辅以全面的表型和遗传评估。我们的发现扩展了FPS的表型谱,揭示新的胎儿表型特征。此外,一个案例强调了这种疾病中潜在的新型遗传模式。最后,我们的观察结果强调了外显子组/基因组测序在具有正常核型和基于阵列的比较基因组杂交(CGH)的罕见多畸形综合征的产前和死后诊断中的有效性.
BACKGROUND: Fontaine progeroid syndrome (FPS, OMIM 612289) is a recently identified genetic disorder stemming from pathogenic variants in the SLC25A24 gene, encoding a mitochondrial carrier protein. It encompasses Gorlin-Chaudry-Moss syndrome and Fontaine-Farriaux syndrome, primarily manifesting as craniosynostosis with brachycephaly, distinctive dysmorphic facial features, hypertrichosis, severe prenatal and postnatal growth restriction, limb shortening, and early aging with characteristic skin changes, phalangeal anomalies, and genital malformations.
METHODS: All known occurrences of FPS have been postnatally observed until now. Here, we present the first two prenatal cases identified during the second trimester of pregnancy. While affirming the presence of most postnatal abnormalities in prenatal cases, we note the absence of a progeroid appearance in young fetuses. Notably, our reports introduce new phenotypic features like encephalocele and nephromegaly, which were previously unseen postnatally. Moreover, paternal SLC25A24 mosaicism was detected in one case.
CONCLUSIONS: We present the initial two fetal instances of FPS, complemented by thorough phenotypic and genetic assessments. Our findings expand the phenotypical spectrum of FPS, unveiling new fetal phenotypic characteristics. Furthermore, one case underscores a potential novel inheritance pattern in this disorder. Lastly, our observations emphasize the efficacy of exome/genome sequencing in both prenatal and postmortem diagnosis of rare polymalformative syndromes with a normal karyotype and array-based comparative genomic hybridization (CGH).