Table 2.
Genotypic and phenotypic description of novel and previously described cases with C2CD3-mediated ciliopathy
| C2CD3 variants and inheritance | Sex | Age at Dx | Clinical diagnosis | Neuronal | Oral | Facial | Digital | Retinal | Renal & hepatic | Skeletal | Other | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Family 1 proband | c.[1365+1G>A];[5090+5G>C] r.[1217_1365del];[1491_5090del] p.[Ser406Argfs*23]; [Ser1652Tyrfs*26] |
M | Prenatal | OFD | DWM; MTS; hyposulcation; subependymal gray matter heterotopia; rudimentary appearing hippocampal formations; DD; hypotonia; microcephaly | Submucous palate, upper lip, maxillary and mandibular alveolar clefting; natal tooth; tongue hamartoma | Microretrognathia; facial dysmorphism | Unilateral hand and bilateral foot postaxial polydactyly | Retinal colobomas | Pelviectasis | None | IUGR, bilateral cryptorchidism PDA; sleep apnea |
| Family 1 sister | c.[1365+1G>A];[5090+5G>C] r.[1217_1365del];[1491_5090del] p.[Ser406Argfs*23]; [Ser1652Tyrfs*26] |
F | UK | OFD | Simplified gyral pattern; limbic system and cerebella hypoplasia; gray matter heterotopia; DD; microcephaly | Ankyloglosssia; bifid tongue with hamartoma; incomplete cleft of upper lip; high narrow palate | Epicanthal folds; mild synophrys; disproportionately large ears | Postaxial polydactyly of hands; pre- and post-axial polydactyly of feet | Optic nerve colobomas; cortical vision impairment; myopia; nystagmus | UK | UK | sleep apnea |
| Family 2 proband | c.[2695G>A];[3342C>T] r.[?];[3160_3344del] p.[Val899Met];[Gly1054Aspfs*7] | F | Prenatal | Fetal encephalocele | Occipital encephalaocele | Bifid tongue | Sloping forehead; microretrognathia; short webbed neck | None | None | None | None | VSD; hypoplastic thyroid |
| Family 2 sister | UK | F | Prenatal | Fetal encephalocele | Encephalocele with brain tissue protrusion | UK | UK | None | None | None | Lumbosacral vertebral defect | NR |
| Family 3 proband | c.[128T>G]; [5227G>T] p.[Leu43Arg];[Gly1743Cys] | M | Prenatal | Joubert-related disorder | MTS; DWM dilation of 3rd and 4th ventricle; midline cerebellar cleft; thin corpus callosum; DD; hypotonia | Malformed lobulated tongue; tight frenulum | Micrognathia; posteriorly rotated low-set ears; bulbous nose with vertical crease | None | Retinal colobomas | None | Shortening of long bones in utero | IUGR; mild epispadias; hypoapnea |
| Thauvin-Robinet (case 1) | c.[184C>T];[184C>T] p.[Arg62*];[Arg62*] | M | UK | OFD14 | MTS; incomplete corpus callosum agenesis; subarachnoid cysts; myelinization defect; ID; microcephaly | Lobulated tongue with hamartoma; cleft tongue; cleft palate; buccal frenulae; absent epiglottis; supernumary teeth | Facial dysmorphism | Bilateral hand postaxial polydactyly; bilateral broad hallux | Retinopathy | None | NR | micropenis |
| Thauvin-Robinet (case 2) | c.[184C>T];[184C>T] p.[Arg62*];[Arg62*] | F | Prenatal | OFD14 | Similar to Thauvin-Robinet case 1 | Similar to Thauvin-Robinet case 1 | Similar to Thauvin-Robinet case 1 | Similar to Thauvin-Robinet case 1 | Similar to Thauvin-Robinet case 1 | Similar to Thauvin-Robinet case 1 | Similar to Thauvin-Robinet case 1 | Cardiac malformation; neonatal death |
| Thauvin-Robinet (case 3) | c.[3085T>G];[3911-2A>T] r.[?];[3911_3914del] p.[Cys1029Gly];[Ala1304Valfs*3] | M | Prenatal | OFD14 | Vermian hypoplasia; mild agenesis of corpus callosum; subarachnoid cyst; microcephaly | Buccal frenulae | Facial dysmorphism | Bilateral hand post axial polydactyly; bilateral broad hallux | NR | Right renal hypoplasia | NR | micropenis |
| Bachmann-Gagescu (case 4) | c.[184C>T];[184C>T] p.[Arg62*];[Arg62*] | UK | UK | Joubert syndrome/OFD-like | UK | Oral frenulae and/or cleft palate | UK | UK | UK | UK | UK | UK |
| Bachmann-Gagescu (case 5) | c.[4951+1G>T];[5267G>A] p.[?];[Gly1756Glu] | UK | UK | Joubert syndrome/OFD-like | UK | Oral frenulae and/or cleft palate | UK | UK | UK | UK | UK | UK |
| Srour (case 6) | c.[5227G>T];[5929C>T] p.[Gly1743Cys];[Arg1977*] | M | UK | Joubert syndrome | MTS; severe global DD; hypotonia; ataxia | NR | NR | NR | NR | None | None | NR |
| Srour (case 7) | c.[5227G>T];[5929C>T] p.[Gly1743Cys];[Arg1977*] | M | UK | Joubert syndrome | MTS; severe global DD; hypotonia; ataxia | NR | NR | NR | Oculomotor apraxia | None | None | Respiratory abnormalities |
| Cortes (case 8) | c.[195G>C];[1429del] p.[Trp65Cys];[Ile477*] | F | Prenatal | Skeletal dysplasia | DWM | High arched palate | Hypertelorism, broad nasal bridge; dysplastic ears; micrognathia | Preaxial polydactyly of feet presenting as duplicated bent hallux; brachydactyly | Micropthalmia | Renal cysts | Short tubular bones; short ribs; trident acetabula | Anterior anus; atypical lung lobulation; mobile cecum |
| Cortes (case 9) | c.[195G>C];[1429del] p.[Trp65Cys];[Ile477*] | M | Prenatal | Skeletal dysplasia | Holoprosencephaly; DWM; dilated cisterna magnum and vermis aplasia; cerebellar hypoplasia; polymicrogyria; hydrocephalus | NR | Facial dysmorphism | Preaxial polydactyly of feet, pre- and post-axial polydactyly of hands | NR | Renal cysts | Short, bent tubular bones; hypoplastic tibia; short ribs; trident acetabula | ASD; atypical lung lobulation; mobile cecum; micropenis/ ambiguous genitalia |
ASD atrial septal defect, DD developmental delay, DWM Dandy–Walker malformation, Dx diagnosis, ID intellectual disability, MTS molar tooth sign, NA not available, NR not reported, PDA patent ductus arteriosis, UK unknown, VSD ventricular septal defect
Data are annotated using hg19, NM_001286577.1, NG_041791.1