Table 1.
Clinical and Genetic Findings of Individuals with KDM4B Variants
| Affected Individual (I)/ Country | I:1 (Italy) | I:2 (USA) | I:3 (Netherlands) | I:4 (Netherlands) | I:5 (France) | I:6 (France) | I:7 (Canada) | I:8 (France) | I:9 (France) |
|---|---|---|---|---|---|---|---|---|---|
| Variant from reference sequence: NM_015015.2 | c.3284C>T (p.Pro1095Leu) | c.2303A>G (p.His768Arg) | c.659T>C (p.Leu220Pro) | c.288C>T (r.287_317del; p.Glu97Thrfs∗66); synonymous variant leading to new donor splice site and frameshift | c.2221dup (p.Glu741Glyfs∗41) | c.1778_1779delAG (p.Glu593Glyfs∗41) | c.664C>T (p.Arg222Trp) | c.371_374del (p.Lys124Thrfs∗48) | c.1907−1G>C (p.?) |
| gnomAD frequency | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| CADD score | 25.4 | 25.6 | 32 | − | − | − | 32 | − | − |
| Inheritance | de novo | de novo | de novo | de novo | de novo | paternally inherited | de novo | de novo | maternally inherited |
| Sex | male | male | female | male | male | female | female | male | male |
| Family history | NC | parents from Middle East and consanguineous | NC | NC | NC | father with learning disabilities | NC | mother and father with mild learning disabilities | mother with a similar phenotype |
| Gross motor delay | + | + | + | + | + | − | + | − | − |
| Fine motor delay | + | + | − | − | − | − | + | + | − |
| Language delay | + | + | + | + | + | + | + | + | − |
| GDD or ID | +, GDD | +, GDD | +, GDD | +, GDD | +, GDD and mild ID | +, GDD and severe ID, IQ = 50 | +, GDD | +, GDD and mild ID, IQ 60–72 | +, mild ID |
| Tone | hypotonia | ND | ND | ND | ND | ND | central hypotonia, peripheral hypertonia | facial hypotonia | ND |
| Seizures | − | +, neonatal seizures, none since then | − | +, seizures starting at 2.5 years | − | − | +, history of infantile spasms starting at 3 weeks | − | − |
| Behavioral concerns | ND | ADHD | behavior concerns, autistic features | ND | history of intermittent aggression with other children | eating disorder; compulsive behavior | ND | aggression, ADHD | − |
| Other neurological abnormalities | − | +, obstructive hydrocephalus s/p shunt placement | +, ataxia, autistic features | − | +, general clumsiness | − | − | − | − |
Abbreviations: +, features are present; −, features are absent; NC, noncontributory; ND, not documented.