Table 1.
Clinical and Neuroradiological Features of Individuals with De Novo CDH2 Pathogenic Variants
| Subjects | Subject 1 | Subject 2 | Subject 3 | Subject 4 | Subject 5 | Subject 6 | Subject 7 | Subject 8 | Subject 9 |
|---|---|---|---|---|---|---|---|---|---|
| CDH2 variant (GenBank: NM_001792.5) | c.1057G>A p.Asp353Asn |
c.1789G>A p.Asp597Asn |
c.1789G>T p.Asp597Tyr |
c.1802A>C p.Asn601Thr |
c.1839C>G p.Cys613Trp |
c.1880A>G p.Asp627Gly |
c.2027A>G p.Tyr676Cys |
c.2563_2564delCT p.Leu855Valfs∗4 |
c.2564_2567dup p.Leu856Phefs∗5 |
| Inheritance | de novo | de novo | de novo | de novo | de novo | de novo | de novo | de novo | de novo |
| Gender | female | male | female | female | male | male | male | female | male |
| Current age, years (deceased) | 13 | 8 | (2 months) | 5 | 3.5 | 11 | 23 | 37 | 12 |
| Neurodevelopment | Gross and fine motor delay | GDD | − | GDD | GDD | GDD | GDD | GDD | fine motor and language delay |
| Intellectual disability | borderline or low average IQ | mild ID | − | moderate ID | moderate ID | no | no | low average IQ | mild ID |
| Neuropsychiatric issues | + | + | − | + | + | + | + | + | − |
| Epilepsy | − | − | − | + | + | − | − | − | − |
| Head circumference | +3.3 SD | +0.9 SD | −0.5 SD | +2.6 SD | −0.5 SD | +2.4 SD | NA | +3.3 SD | −1.7 SD |
| Axial hypotonia | − | + | − | − | + | + | − | − | − |
| Appendicular hypertonia | − | + | − | − | + | + | − | − | − |
| Hyposmia | + | − | − | − | − | − | + | + | − |
| Sensorineural hearing loss | − | + | − | − | − | − | − | − | + |
| Roving eye movements | − | − | + | − | + | − | − | − | − |
| Dysmorphisms | − | + | + | + | minor | + | + | + | minor |
| ACC | + | + | + | + | mild CC hypoplasia | + | − | + | + |
| Hypothalamic adhesion | + | + | − | + | − | − | − | + | + |
| Interhemispheric cyst | − | + | + | − | − | − | − | − | − |
| PNH | − | + | + | + | − | − | − | + | − |
| Tentorium hypo−dysplasia | − | + | + | + | − | − | − | + | − |
| Cardiovascular abnormalities | + AV canal defect |
+ mild tricuspidal regurgitation |
+ AV canal defect, mild hypoplastic aortic arch |
− | + dextrocardia, right pulmonary artery hypoplasia, atrial flutter |
− | + small pericardial effusion |
+ aortic coarctation |
+ aortic coarctation |
| Eye abnormalities | + strabismus, bilateral cataracts |
+ Duane anomaly, right ptosis, bilateral upgaze limitation |
− | + Peters anomaly, right esotropia |
− | + Peters anomaly, strabismus, nystagmus |
+ myopia |
+ strabismus, mild hyperopia |
+ astigmatism, hyperopia |
| Urogenital malformations | − | micropenis | − | − | − | right cryptorchidism | bilateral cryptorchidism | − | bilateral cryptorchidism |
| Other | salt hypogenusia, C5-C6 partial fusion, imperforate anus. de novo missense in DNM1 (p.Leu134Met) |
− | − | aplasia cutis congenita at vertex, shoulder Sprengel type deformity | pulmonary sequestration | − | mirror movements, umbilical and inguinal hernias, bilateral absence of shoulder muscles, hip dysplasia, scoliosis, hyperlordosis, joint hypermobility, pes planus | scapular winging, right shoulder Sprengel type deformity, mild scoliosis, noise sensitivity |
Abbreviations are as follows: ADHD, attention deficit hyperactivity disorder; AV, atrioventricular; GDD, global developmental delay; ID, intellectual disability; CC, corpus callosum; ACC, agenesis of corpus callosum; PNH, periventricular nodular heterotopia; NA, not available; SD, standard deviation.