Table 1
Clinical Features of Subjects with CDK8 Mutations
| Subject # | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Gender | f | m | m | f | m | f | m | m | f | m | f | m |
| Age (years) | 9 | 2.9 | 8 | 7.6 | 0.1 | 0.8 | 16.7 | 12.7 | 6.8 | 5.4 | 12 | 3.5 |
| Mutation | c.79G>C | c.85C>G | c.88G>A | c.185C>T | c.185C>T | c.185C>T | c.185C>T | c.185C>T | c.291T>G | c.533G>A | c.578T>G | c.669A>G |
| Substitution | p.Val27Leu | p.Arg29Gly | p.Gly30Ser | p.Ser62Leu | p.Ser62Leu | p.Ser62Leu | p.Ser62Leu | p.Ser62Leu | p.Phe97Leu | p.Arg178Gln | p.Val193Gly | p.Ile223Met |
| De novo | yes | yes | yes | yes | yes | yes | NA | NA | yes | yes | yes | yes |
| Facial dysmorphism | + | + | + | + | + | + | + | + | − | + | + | + |
| Hypotonia, motor delay, and/or walking difficulty | + | + (axial) | + | + | NA | + (axial) | + (bilateral pes planus surgery) | + | + | + | + | + |
| Brain MRI or CT | normal | thin corpus callosum | normal | ACC | NA | ACC | NA | ACC | non-specific | NA | normal | NA |
| Ophthalmic: ptosis | + | − | − | − | − | − | − | − | − | − | + | − |
| Strabismus | + | + | + | − | − | − | − | + | − | − | − | − |
| Myopia | + | + | − | + | − | − | + (severe) | + | − | − | + | − |
| Impaired vision | + | − | − | − | − | − | + | − | − | − | − | − |
| Sensorineural hearing loss | moderate | moderate | − | − | NA | − | − | − | severe (unilateral) | NA | (glue ear) | − |
| Intellectual disability | mild (SEN school) | moderate to severe | moderate to severe (SEN school) | moderate | NA | NA; moderate motor delay | mild to moderate (SEN school) | moderate (SEN school) | moderate | moderate | mild (normal school) | NA; moderate motor delay |
| Behavioral disorder | ADHD | − | ASD, ADHD, sleep disorder | ADHD, sleep disorder | NA | NA | ASD | ASD, ADHD | ASD | happy disposition | attention seeking, volatile | ASD |
| Epilepsy | − | − | − | − | − | − | complex partial | − | general and focal | − | − | − |
| Feeding difficulties | infancy only | gastrostomy-fed | congenital pyloric stenosis | previous gastrostomy | NA | − | reflux | reflux, regurgitation | reflux, episodic vomiting | − | episodic vomiting | − |
| Congenital heart disease (S indicates age at surgery) | − | − | perimembraneous VSD, double orifice mitral valve | hypoplastic left heart (S: 4 days, 3 months, 4 years) | atrial septal defect, VSD, bicuspid aortic valve, hypoplastic aortic arch (S: unknown) | coarctation of the aorta, subaortic stenosis, mitral stenosis (S: 5 months) | tetralogy of Fallot (S: 9 months) | − | − | − | − | VSD, PFO |
| Other | metopic synostosis | anterior anus, recto-perianal fistula | undescended testes | rectal mucosal prolapse |
Abbreviations and symbols are as follows: + = present; − = absent; NA = information not available; f = female; m = male; ACC = agenesis of the corpus callosum; ADHD = attention deficit-hyperactivity disorder; ASD = autism spectrum disorder; PFO = patent foramen ovale; SEN = special educational needs; and VSD = ventricular septal defect.