Table 1.
Prenatal cases for which WES demonstrated a likely pathogenic or pathogenic variant. For each case, the fetal phenotype and the organ system involved are described and the affected gene and variant, the inheritance mode, the associated syndrome and the outcome of the pregnancy are listed. AD: autosomal dominant; AR: autosomal recessive; hom: homozygous; IF: incidental finding; IUGR: intrauterine growth restriction; LB: live birth; mat: maternal; NT: nuchal translucency; pat: paternal; path: pathogenic; TOP: termination of pregnancy.
| Case No. | Phenotype | Phenotypic Group |
Gene | Variant | Inheritance | Classification | Associated Syndrome | Outcome |
|---|---|---|---|---|---|---|---|---|
| 1 | Abnormal ears, bilateral talipes equinovarus | skeletal | KMT2D | c.450G > A p.(Trp150*) |
AD–de novo | path | Kabuki syndrome 1 (OMIM# 147920) |
TOP |
| 8 | IUGR, oligodactyly left hand, hypoplastic ray right hand |
skeletal | FANCG | c.115C > T p.(Arg39*) |
AR–hom | path | Fanconi anemia, complementation group G (OMIM# 614082) |
TOP |
| 10 | Rhizomelic shortening and bowing of the long bones, microretrognathia and clenched hands | skeletal | COL2A1 | c.2710C > T p.(Arg904Cys) |
AD–pat | path | Stickler syndrome type I (OMIM# 108300) | LB |
| 12 | Edema, rocker bottom foot, retrognathia, abnormal thorax and ribs, increased NT |
multisystem | CHRNA1 | c.548A > G p.(Asp183Gly) |
AR–hom | likely path | Multiple pterygium syndrome, lethal type (OMIM# 253290) | TOP |
| 23 | Hydrops, acites, hydrothorax | hydrops | RIT1 | c.297T > A p.(Phe99Leu) |
AD–de novo | path | Noonan syndroom 8 (OMIM# 615355) |
TOP |
| STXBP1 | c.875G > A p.(Arg292His) |
AD–de novo | path (IF) | Developmental and epileptic encephalopathy type 4 (OMIM# 612164) |
||||
| 26 | Olivopontocerebellar hypoplasia, tetralogy of Fallot, hypospadias |
multisystem | THOC6 | c.298T > A p.(Trp100Arg) |
AR–het (mat) | path | Beaulieu-Boycott-Innes syndrome (OMIM# 613680) |
TOP |
| THOC6 | c.700G > C p.(Val234Leu) |
AR–het (mat) | path | |||||
| THOC6 | c.824G > A p.(Gly275Asp) |
AR–het(mat) | path | |||||
| THOC6 | c.569G > A p.(Gly190Glu) |
AR–het (pat) | path | |||||
| 28 | Fetal akinesia, hypotonia, rocker-bottom feet, hydrops, hydrothorax, ascites |
multisystem | MUSK | c.2201G > T p.(Gly734Val) |
AR–hom | likely path | Fetal akinesia deformation sequence 1 (OMIM# 208150) |
TOP |