In Brief BACKGROUND: Partial deletion of the long arm of the chromosome 13 is a rare chromosomal aberration and may present with microcephaly, colobomata, microphthalmia, distal limb and digital anomalies, cardiac defects, brain and urogenital malformations, anal atresia and growth restriction. CASE: We report such a case in 25th week of gestation referred for sonographic examination which revealed growth restriction, microcephaly, Dandy-Walker malformation, right microphthalmia, micrognathia, marked nuchal edema, four fingers–oligodactyly in feet and in hands with thumb aplasia and ambiguous genitalia. Chromosome analysis identified chromosome 13q deletion [46 XY del (13) (13q31.2/q32.1 → qter)]. Postmortem examination confirmed prenatal findings and showed aniridia, low-set ears, cryptorchidism, and anal atresia. CONCLUSION: Detection of Dandy-Walker malformation, microphthalmia, oligodactyly with thumb aplasia and growth restriction during prenatal ultrasonography should be a reminder of deletion of chromosome 13q and warrant cytogenetic analysis. Fetus with findings of Dandy-Walker malformation, asymmetric microphtalmia, oligodactyly with thumb aplasia and intrauterine growth restriction during prenatal sonographic evaluation should be a reminder of the 13q-syndrome and warrant cytogenetic analysis.
The 22q11 deletion syndrome has an incidence of one in 2000 to 7000 livebirths and also known as DiGeorge and Velocardiofascial syndrome. The overlapping syndrome is associated with a highly variable phenotype despite the uniform point mutations in the TBX1 gene and is often diagnosed with fluorescence in situ hybridisation (FISH). Congenital heart disease (CHD) is reported with an estimated high rate of 74%, conotruncal anomalies being the most detected ones. A retrospective study of all fetuses with 22q11 microdeletion syndrome were included between 2010 and 2016. All 26 cases had detailed fetal sonogram and were offered karyotyping, FISH or array CGH. Mean gestational age was 22 weeks (min 17–max 31 ws). TOF (n = 12, 46%) was the most detected heart defect of 26 cases, and other defects included 15% (n = 4) RAA, 0.07% (n = 2) AoCoa, 0.07% (n = 2) truncus arteriosus, respectively. In 2 cases, ARSA was the only detected heart defect, and in another 2 cases no congenital heart defect was diagnosed. Prenatal diagnosis was confirmed by FISH only in 61.1% (n = 16) of all cases. In 2 cases, karyotyping and FISH results were normal and the diagnosis confirmed by array CGH. Detected mutations in fifteen cases were de novo, however in only one case, a 22q11 deletion of maternal origin was identified. In this case, the mother's other son was diagnosed 22q11 deletion syndrome after the current pregnancy. Mild hydronephrosis (n = 4), polyhydramniosis (n = 4) and thymus aplasia/hypoplasia (n = 10) were the most detected additional ultrasonography findings. A half (n = 13) of all cases were TOP, and 23% (n = 6) were livebirth. Pregnancy outcomes in 23% (n = 6) of all cases are unknown due to lost to follow-up. Our results may suggest that, when ARSA is detected as an isolated fetal echocardiographic finding, it may justify investigation for 22q11 microdeletion syndrome, and not only aneuploidy. Array CGH may have diagnostic sensitivity superior to that of FISH in fetuses with CHD associated with del22q11 syndrome.
What is already known on this topic?Androgen insensivity syndrome and 5α-reductase deficiency are the most common causes of 46,XY disorders of sexual development.They can present as indistinguishable phenotypes that usually necessitate molecular analyses for the definitive diagnosis in the prepubertal period. What this study adds?Testosterone to dihydrotestosterone ratio may lead to diagnostic confusion.Genetic analysis for actual diagnosis seems to be essential.Four novel androgen receptor variants were identified in this Turkish pediatric population.
Sudden death risk in Williams syndrome (WS) patients has been shown to be 25-100 times higher than in the general population. This study aims to detect coronary artery anomalies and myocardial perfusion defects in WS patients using noninvasive diagnostic methods.This study features 38 patients diagnosed with WS. In addition to physical examination, electrocardiography, and echocardiography, computed tomography (CT) angiography and rest/dipyridamole stress technetium-99m sestamibi ((99m)Tc-sestamibi) single photon emission computed tomography (SPECT) myocardial perfusion scintigraphy (MPS) were performed.Twenty-one (55%) patients were male; 17 (45%) were female. The average patient age was 12 ± 5 years (2.5-26 years); the average follow-up period was 7.2 ± 4.2 years (6 months-18 years). Cardiovascular abnormalities were found in 89% of patients, the most common one being supravalvar aortic stenosis (SVAS). CT angiography revealed coronary anomalies in 10 (26%) patients, the most common ones being ectasia of the left main coronary artery and proximal right coronary artery as well as myocardial bridging. SVAS was present in 80% of patients with coronary artery anomalies. (99m)Tc-sestamibi SPECT MPS revealed findings possibly consistent with myocardial ischemia in 29% of patients, and ischemia in 7 out of 10 patients (70%) with coronary anomalies shown on CT angiography (p = 0.03).Coronary artery abnormalities are relatively common in WS patients and are often accompanied by SVAS. CT angiography and dipyridamole (99m)Tc-sestamibi SPECT MPS seem to be less invasive methods of detecting coronary artery anomalies and myocardial perfusion defects in WS patients.
Amaç: Hücre büyüme, farklılaşma, yaşlanma ve siklus düzenlenmesinde önemli rol oynayan RAS-MAPK (Rat-sarcoma-Mitogen-activated-protein-kinase) yolağında bulunan 29 gendeki dominant patojenik varyantların yol açtığı klinik grup “Rasopatiler” olarak adlandırılır. En sık gözleneni Noonan sendromu (NS)’dur. Olguların ~%50’sinde NS ilişkili PTPN11 varyantları saptanır ve bu varyantların %90’ı peptidin N-önündeki ilk SH2 ve C-yönündeki katalitik domainini kodlayan bölgelerde ortaya çıkar. Prenatal evrede artmış nukal kalınlık (NT) ve ayrıca kistik higroma, plevral efüzyon ve asit gibi lenfatik sistem anomalilerinin yanı sıra kardiyak anomaliler, polihidramniyos, ekstremite kısalığı ve makrosefali NS’nin bulguları arasında sayılır. PTPN11 ilişkisi, kromozom anomalisi dışlanmış NT bulgusu olan fetusların %2-3’ünde, ek NS bulgusu olanlarda ise >%10 olarak bildirilmektedir. Gereç ve Yöntem: Çalışmamızda, NS ilişkili Ultrasonografi (USG) bulgusu olan, kromozom anomalisi dışlanmış 246 prenatal olguda, farklı yaklaşımlarla çalışılan PTPN11 gen analiz sonuçları retrospektif olarak değerlendirildi. Olguların 200’ünde genin hedef ekzonları (ekzon 3, 4, 7, 8, 13 ve 14), 46 olguda ise tüm gen Sanger dizileme yöntemi ile incelendi. Bulgular: Genel seride beş olguda (%2) ikisi novel olan (p.P107S ve p.M504T) beş farklı varyant hedeflenmiş ekzonlarda saptandı. Bu beş olgunun ikisinde izole NT ve üçünde çoklu USG bulguları mevcuttu. PTPN11 varyantı saptanmayan altı olguda, Rasopati ilişkili diğer dört genin hedef bölge analizinde, iki olguda SOS1 ve gebelik terminasyonu yapılan üç olgunun birinde hedeflenmiş gen panel testinde RAF1 geninde ilişkili patojenik varyantlar saptandı. NS ilişkili patojenik varyant saptama oranı hem izole NT grubunda hem de çoklu USG bulgulu grupta %2,3 idi. Tartışma: Rasopatilerin %50 sinden sorumlu olan PTPN11 genindeki patojenik varyantların %90’ı hedef ekzonlarda yer almaktadır. Bu nedenle, ilk aşamada PTPN11 hedef ekzon analizi yapılmasının, patogenezin açıklanamadığı olgularda ise genin diğer ekzonlarının ve Rasopati ilişkili diğer genlerin incelenmesinin fayda-maliyet açısından uygun bir yaklaşım olduğu belirlendi.
