Capkova Pavlina, Santava Alena, Markova Ivana, Stefekova Andrea, Srovnal Josef, Staffova Katerina, Durdová Veronika
Department of Medical Genetics, University Hospital Olomouc, I.P.Pavlova 6, Olomouc, Czech Republic.
Department of Obstetrics and Gynaecology, University Hospital Olomouc, Olomouc, Czech Republic.
Mol Cytogenet. 2017 Dec 28;10:47. doi: 10.1186/s13039-017-0351-3. eCollection 2017.
Interstitial microdeletion 14q22q23 is a rare chromosomal syndrome associated with variable defects: microphthalmia/anophthalmia, pituitary anomalies, polydactyly/syndactyly of hands and feet, micrognathia/retrognathia. The reports of the microdeletion 14q22q23 detected in the prenatal stages are limited and the range of clinical features reveals a quite high variability.
We report a detection of the microdeletion 14q22.1q23.1 spanning 7,7 Mb and involving the genes and in the foetus by multiplex ligation-dependent probe amplification (MLPA) and verified by microarray subsequently. The pregnancy was referred to the genetic counselling for abnormal facial profile observed in the first trimester ultrasound scan and micrognathia (suspicion of Pierre Robin sequence), hypoplasia nasal bone and polydactyly in the second trimester ultrasound scan. The pregnancy was terminated on request of the parents.
An abnormal facial profile detected on prenatal scan can provide a clue to the presence of rare chromosomal abnormalities in the first trimester of pregnancy despite the normal result of the first trimester screening test. The patients should be provided with genetic counselling. Usage of quick and sensitive methods (MLPA, microarray) is preferable for discovering a causal aberration because some of the CNVs cannot be detected with conventional karyotyping in these cases. . Literature review of the genotype-phenotype correlation in similar reports leads us to the conclusion that dosage imbalance of the chromosomal segment 14q22q23 (especially haploinsuffiency of the genes and ) contributes significantly to orofacial abnormalities. Association of the region with the Pierre Robin sequence appears to be plausible.
间质微缺失14q22q23是一种罕见的染色体综合征，与多种缺陷相关：小眼症/无眼症、垂体异常、手足多指（趾）/并指（趾）、小颌畸形/后缩颌。产前阶段检测到14q22q23微缺失的报告有限，临床特征范围显示出相当高的变异性。
我们报告通过多重连接依赖探针扩增（MLPA）在胎儿中检测到一个跨度为7.7Mb、涉及基因 和 的14q22.1q23.1微缺失，随后通过微阵列验证。该孕妇因孕早期超声扫描发现面部轮廓异常、孕中期超声扫描发现小颌畸形（怀疑皮埃尔·罗宾序列）、鼻骨发育不全和多指（趾）而被转诊至遗传咨询门诊。应父母要求终止了妊娠。
产前扫描检测到面部轮廓异常，尽管孕早期筛查试验结果正常，但仍可为妊娠早期罕见染色体异常的存在提供线索。应向患者提供遗传咨询。对于发现因果畸变，使用快速灵敏的方法（MLPA、微阵列）更为可取，因为在这些病例中，一些拷贝数变异无法通过传统核型分析检测到。对类似报告中基因型-表型相关性的文献综述使我们得出结论，染色体片段14q22q23的剂量失衡（尤其是基因 和 的单倍剂量不足）显著导致口面部异常。该区域与皮埃尔·罗宾序列的关联似乎是合理的。
