Table 1.
Clinical findings of patients with CSNK2B variants
| Individuals | Subject 1 | Subject 2 | Subject 3 | Subject 4 | Subject 5 |
|---|---|---|---|---|---|
| CSNK2B variant (GenBank: NM_001320.7) | c.94G>C (p.Asp32His) | c.94G>A (p.Asp32Asn) | c.94G>A (p.Asp32Asn) | c.374C>G (p.Ser125∗) | c.367+5delG (p.Leu124Aspfs∗26 and p.Leu98Alafs∗11)a |
| Inheritance | de novo | de novo | unknown | de novo | unknown |
| Sex | female | female | female | male | female |
| Age (years) | 19 | 10 | 2 | 7 | 30 (deceased) |
| Ancestry | Caucasian | Caucasian | Caucasian | Israeli | Caucasian |
| Parenteral consanguinity | – | – | – | – | – |
| Measurements (at birth) | |||||
| Gestational age (weeks) | 41 | 39 | 39 | 40 | N/A |
| Height (SD) | −1.9 | −0.8 | −2.8 | N/A | −1.33 |
| Weight (SD) | −1.3 | −1.1 | −0.8 | N/A | 0.21 |
| OFC (SD) | −0.9 | N/A | −1.2 | N/A | N/A |
| Measurements (at age) | 12 years | 9 years | 2 years | 6 years | 30 years |
| Height (SD) | −3.3 | +0.11 | −0.26 | −0.32 | −0.8 |
| Weight (SD) | −1.9 | +1.53 | +0.21 | −0.41 | −2.03 |
| OFC (SD) | −1.7 | +0.9 | −0.24 | +0.36 | N/A |
| Neurological features | |||||
| Global developmental delay | + | + | + | + | + |
| Intellectual disability | + (moderate) | + | Developmental delay | + | + |
| Speech impairment | + (moderate) | + | + | + | N/A |
| Epileptic seizures | + (tonic-clonic) | EEG abnormalities | – | + | + (tonic-clonic, myoclonic, clonic, absence seizures) |
| Facial features | |||||
| Deep-set eyes | + | + | + | – | eye movement issues, hyperopia, myopia, lazy eye |
| Nasal bridge | broad | depressed | broad, depressed | prominent | prominent |
| Hypoplastic alae nasi | + | + | + | + | + |
| Mouth | thin lips | thin lips | arched upper lip | – | – |
| Prognathism | + | + | + | – | + (class III underbite) |
| Pointed chin | + | + | + | – | + |
| Ears | small, prominent antitragus | symmetric protruding | asymmetric: left cupped, right overfolded | protruding | – |
| Hands and feet | |||||
| Fingers | brachydactyly cutaneous syndactyly of fingers 3/4/5 (required surgery) including osseous syndactyly of distal phalanges 3/4 |
tapering of fingers, most prominent on fifth fingers | brachydactyly contractures of the left hand first, fourth, and fifth fingers (required surgery on first and fourth); initial reports of mild right-sided first and second digit involvement |
– | – |
| Toes and feet | brachydactyly 2–5 syndactyly 2–3 | clinodactyly of toes 3/4/5 pronation of feet |
small feet mild inversion and pronotion of feet |
– | flat feet |
| Ectodermal anomalies | |||||
| Hair | thin | thin | sparse temporal, anterior thin, posterior coarse | hypopigmentation, partial | – |
| Teeth | hypodontia | small teeth | delayed eruption | – | |
| Cardiac defect | Ebstein’s anomaly and atrial septal defect | WPW | fenestrated atrial septal defect | mild cardiac defect | – |
| Others | IgA nephropathy; nocturnal enuresis | emotional regulation disorder, low attention span | hypotonia, low tone, memory impairment, anxiety, depression, obsessive compulsive disorder, proprioception issues | ||
+, present; −, not present/no abnormality; N/A, not available; OFC, occipital-frontal circumference; SD, standard deviation; WPW, Wolff-Parkinson-White.
a
Variants at protein levels resulted from minigene splicing assay.