Table 1.
Genetic and Major Clinical Features
| Proband A | Proband B | Proband C | Subject II:2 of Family C | |
|---|---|---|---|---|
| CIT variant (hg19, GenBank: NM_007174.2) | chr12: 120,260,623 | chr12: 120,313,935–120,313,944 | chr12: 120,295,329 and chr12: 120,288,021 | chr12: 120,295,329 and chr12: 120,288,021 |
| c.1111+1G>A | c.29_38delATCCTTTGGA | c.412C>T and c.473C>G | c.412C>T and c.473C>G | |
| – | p.Asn10Metfs∗15 | p.Gln138∗ and p.Pro158Arg | p.Gln138∗ and p.Pro158Arg | |
| GERP score | 5.900 | NA | 4.660 and 5.280 | 4.660 and 5.280 |
| CADD score | 31.000 | NA | 38.000 and 27.800 | 38.000 and 27.800 |
| Gender | male | male | male | male |
| Gestational length | full term | full term | full term | pregnancy terminated at GW 29 + 2 |
| Birth weight | 2.6 kg (−2 SDs) | 1.730 kg (−4 SDs) | 2.92 kg (−1 SD) | NA |
| Birth length | unknown (home birth) | 27.2 cm crown to rump (−2.5 SD) | 46 cm (−2 SDs) | NA |
| Birth head circumference | unknown (home birth) | 24 cm (−8 SDs) | 30 cm (−3.5 SDs) | NA |
| Head circumference at most recent evaluation | 27 cm (−11 to −12 SDs) measured at 3.5 months | NA | 43 cm (−6.5 SDs) measured at 10 years | NA |
| Brain abnormalities | MRI revealed microlissencephaly, agenesis of corpus callosum, cerebellar and brainstem hypoplasia, and T2 hyperintensity of the whole white matter | autopsy revealed microlissencephaly, absent corpus callosum, hindbrain and cerebellum hypoplasia, cerebral cortex hypoplasia, and comparatively large ventricles; a detailed neuropathology is included in the main text | MRI revealed microcephaly, a simplified gyral pattern, and cerebellar and brainstem hypoplasia | fetal MRI revealed microcephaly, a biparietal diameter equivalent to that of a fetus of 23 GWs, and gyration equivalent to a that of a fetus of 26 GWs |
| Neurological findings | hypertonia of upper and lower extremities, axial hypotonia, increased DTRs, and spastic tetraplegia | NA | hypertonia of upper and lower extremities and brisk DTRs in the lower extremities | NA |
| Seizures | no | NA | no | NA |
| Intellectual disability | not assessed | NA | moderate to severe ID with mild autistic features | NA |
| Development | delayed | NA | delayed | NA |
| Dysmorphisms | hypotelorism, sloping forehead, and relatively large ears | prominent occiput, absent fontanelle, large ears, wide nasal bridge, prominent upper lip, high-arched palate, cloudy corneas, right-sided single palmar crease, and small nails | sloping forehead, prominent nose, and relatively large ears | NA |
| Status | unknown | died 1 day after birth | alive | terminated pregnancy |
World Health Organization Child Growth Standards were applied for weight, height, and head circumference. Abbreviations are as follows: DTR, deep tendon reflex; GW, gestational week; and NA, not available.