Table 2.
Diagnoses made with Next Generation Sequencing based tests.
| ID | M/F | Clinical features | Suspected diagnosis | Prenatal indication | Invasive prenatal diagnostics | Diagnostic techniques implemented | Genetic diagnosis | Clinical diagnosis | TAT (days) | Effect of diagnosis |
|---|---|---|---|---|---|---|---|---|---|---|
| 505 | M | Congenital cardiomyopathy | LEOPARD syndrome, Bardet-Biedl syndrome, isolated cardiomyopathy | US | SNP, T (DCM)* | LP MYH7, AD, c.2711G>A, p.(Arg904His) de novo | Hypertrophic and dilating cardiomyopathy | 28 | Reproductive information for parents, screening family members for individual clinical risk | |
| 511 | F | Congenital omphalocele, dysmorphic features | Beckwith-Wiedemann syndrome | US | SNP, T (CDKN1C), T (LIT1)*& | Hypomethylation of LIT1 | Beckwith-Wiedemann syndrome | 19 | Reproductive information for parents, prognosis, follow-up advice according to published guidelines and/or recommendations | |
| 544 | F | Respiratory distress, distinctive dysmorphic features | Treacher-Collins syndrome | T (HPO)* | P POLR1D, AD, c.259C>T, p.(Arg87*) pat | Treacher-Collins syndrome type 2 | 14 | Reproductive information for parents, screening family members for genetic risk (offspring) | ||
| 552 | M | Polydactyly, bilateral cystic kidney malformation, dysmorphic features | Ciliopathy, cystic fibrosis | SNP, OMOM*#, T (CFTR) | P HNF1B, AD, c.541C>T, p.(Arg181*) pat | Renal cysts and diabetes syndrome | 20 | Reproductive information for parents, prognosis, follow-up advice according to published guidelines and/or recommendations | ||
| 563 | M | Cryptorchidism, clubfoot, dysmorphic features | Partial or mosaic trisomy 13/18, chromosomal or monogenic syndromes | US | SNP, OMOM*# | P MYH3, AD, c.533C>T, p.(Thr178Ile) de novo | Freeman-Sheldon syndrome | 27 | ||
| 574 | M | Pulmonary valve stenosis, obstructive hypertrophic cardiomyopathy, cryptorchidism, dysmorphic features | Noonan syndrome, disorders of sex development | US | SNP, OMOM*# | P RAF1, AD, c.770C>T, p.(Ser257Leu) de novo | Noonan/LEOPARD syndrome | 31 | Reproductive information for parents | |
| 584 | M | Arthrogryposis multiplex congenita, dysmorphic features | Amyoplasia congenita, distal arthrogryposis, fetal akinesia/ hypokinesia sequention, cerebro-oculo-facio-skeletal syndrome, chromosomal aberration, Escobar syndrome, trisomy 18 | US | OMOM*# | P ASCC1, AR, c.710+1G>A | Spinal muscular atrophy (SMA) with congenital fractures type 2 | 38 | Reproductive information for parents, prognosis, follow-up advice according to published guidelines and/or recommendations | |
| 610 | F | Seizures, dysmorphic features | Neonatal convulsions/epileptic encephalopathy, chromosomal aberration | SNP, T (EPI/BFNC)*, T (EPI/EIEE)* | P KCNQ3, AD, c.988C>T, p.(Arg330Cys) de novo | (Benign) familial neonatal convulsions | 17 | Reproductive information for parents, prognosis, follow-up advice according to published guidelines and/or recommendations | ||
| 617 | M | Multiple abnormalities of the vertebrae, dysmorphic features | Spondylocostal dysostosis, VACTERL-association, CHARGE syndrome, Simpson-Golabi-Behmel syndrome, Goldenhar syndrome, chromosomal aberration | US | SNP, T (HPO), OMOM* | LP PTPN11, AD, c.1282G>A p.(Val428Met) de novo; VUS ROBO2, AD, c.3266C>T p.(Thr1089Met) de novo; VUS TCF4, AD, c.1319G>C p.(Gly440Ala) de novo | PTPN11-associated syndrome | 108 | Reproductive information for parents | |
| 619 | F | Intestinal obstruction | Cystic fibrosis and pre-symptomatic testing for autosomal dominant polycystic kidney disease | T (CFTR), T (PKD1)*$ | PKD1, AD, c.7376G>A p.(Gly2459Asp), pat | Autosomal dominant polycystic kidney disease | 102 | Reproductive information for parents | ||
| 620 | F | Cardiac malformation, dysmorphic features | No specific syndromic diagnosis suspected | SNP, OMOM*# | LP NR2F2, AD, c.1187T>A, p.(Ile396Asn) de novo | Heritable congenital heart defects, type 4 | 52 | Reproductive information for parents, prognosis, follow-up advice according to published guidelines and/or recommendations | ||
| 637 | F | Hydrocolpos, hyperechogenic kidneys with cysts in the renal pyramids, dysmorphic features | HDR syndrome, McKusick-Kaufman syndrome, Bardet-Biedl syndrome | US | T (GATA3)*@ | P GATA3, AD, c.404del p.(Pro135fs), mat | Hypoparathyroidism, sensorineural deafness and renal disease (HDR-syndrome) | 87 | Reproductive information for parents, prognosis, follow-up advice according to published guidelines and/or recommendations | |
| 659 | M | Cardiac malformation, diaphragmatic hernia, absent gall bladder, vertebral and costal abnormalities, incomplete ossification of the sternum, dysmorphic features | Pentalogy of Cantrell | SNP, OMOM* | P YY1, AD, c.568_581del p.(Ala190Argfs*34) de novo | Gabriele de Vries syndrome | 27 | Reproductive information for parents, screening family members for individual clinical risk | ||
| 671 | F | Minor omphalocele, hypospadias, multiple sacral dimples, cryptorchidism, dysmorphic features | Beckwith-Wiedemann syndrome, Pit-Hopkins syndrome, glycogen storage disease, Fontaine progeroid syndrome | US | QF, SNP, OM | Re-analysis prenatal OMOM*, T (LIT1)& | P CDKN1C c.726dupG p.(His243Alafs*43) AD, mat | Beckwith-Wiedemann syndrome | 63 | Reproductive information for parents, prognosis, follow-up advice according to published guidelines and/or recommendations |
| 673 | M | Irregular tonus, retinal petechia, clubfeet, dysmorphic features | Chromosomal aberration, monogenic neuromuscular disease, monogenic metabolic disease, Ehlers-Danlos syndrome, clotting disease | US, NIPT | SNP, OMOM, T (DMPK)*@ | 3'UTR CTG(n>150) repeat DMPK | Myotonic dystrophy type 1 | 28 | Reproductive information for parents, prognosis, follow-up advice according to published guidelines and/or recommendations |
TAT, Turnaround time; US, Abnormal ultrasound; NIPT, normal non-invasive prenatal test; QF, quantitative fluorescent polymerase chain reaction; SNP, single nucleotide polymorphism array; OMOM, OMIM mendelian targeted sequencing; T, phenotype-based targeted sequencing; DCM, with specific panel: dilated cardiomyopathy in children; CDKN1C, cyclin dependent kinase inhibitor 1C; LIT1, long QT intronic transcript 1; HPO, human phenotype ontology; CFTR, cystic fibrosis; EPI/BFNC, benign familial neonatal/infantile convulsions; EPI/EIEE, (Early Infantile) Epileptic Encephalopathy; PKD1, polycystin 1; GATA3, GATA binding protein 3; DMPK, DM1 protein kinase;
(*)
, diagnosed using;
(#)
, OM as first tier;
(&)
, technique carried out in University Medical Centers Amsterdam;
($)
, technique carried out in Leiden University Medical Center;
(@)
, technique carried out in University Medical Center Nijmegen; (mat), maternal; (pat); paternal; LP, likely pathogenic; P, pathogenic; AD, autosomal dominant; AR, autosomal recessive.