Table 1.
Clinical and genetic features of 25 patients with de novo DHDDS variants
| Patienta | DHDDS variant | Presenting symptoms | Cognitive and psychiatric features | Epilepsyb | Movement disorder |
|---|---|---|---|---|---|
| 1/M First mo/39 y | c.632G>A, p.(Arg211Gln) | Hypotonia, GDD, tremor, myoclonus | Severe ID, autistic traits, impulsivity, anxiety, cognitive decline, catatonia | 5 y/Gen/absence/no | Tremor, ataxia, parkinsonism, dystonia |
| 2/F 1 y/7.3 y | c.632G>A, p.(Arg211Gln) | GDD, tremor, myoclonus | Moderate ID | – | Tremor, myoclonus |
| 3/M 1 y/6 y | c.110G>A, p.(Arg37His) | Hypotonia, GDD, tremor, epilepsy | Mild ID; hyperactivity | 1 y/Gen/FS, My, MA, absence/no | Tremor, ataxia |
| 4/F 10 mo/13 y | c.632G>A, p.(Arg211Gln) | GDD, epilepsy | Severe ID; autistic traits, anxiety | 10 mo/Gen/GTC, absence/yes | Tremor, ataxia |
| 5/M 6 mo/4.5 y | c.632G>A, p.(Arg211Gln) | Hypotonia, tremor, joint laxity | moderate ID; hyperactivity | – | Tremor, ataxia, spasticity |
| 6/M 15 mo/26 y | c.632G>A, p.(Arg211Gln) | DD, tremor, ataxia | Severe ID, cognitive decline, psychosis | 10y/Gen/GTC/no | Tremor, myoclonus, parkinsonism, dystonia, spasticity |
| 7/M 11 mo/19 y | c.109C>T, p.(Arg37Cys) | Epilepsy, GDD | Severe ID | 11 mo/Gen/My, At, absence, GTC/yes | Tremor, myoclonus, chorea |
| 8/F 1.5 y/31 y | c.109C>T, p.(Arg37Cys) | FS, GDD | Moderate ID, ADHD, anxiety, oppositional behaviour, autistic traits | 2 y/Gen/GTC, Tn, absence/yes | Tremor, ataxia, myoclonus, dystonia |
| 9/M 2 y/16 y | c.698C>G, p.(Pro233Arg) | DD, tremor, neurological regression | Mild ID, OCD | 10 y/Gen/Tn/no | Chorea, myoclonus |
| 10/M 7 mo/6.5 y | c.110G>A, p.(Arg37His) | GDD, neurological regression, FS | Severe ID, ASD | 4y/Gen/Absence, At/no | Stereotypies |
| 11/F First mo/24 y | c.632G>A, p.(Arg211Gln) | GDD, epilepsy, myoclonus, ataxia | Severe ID, ADHD | 11 mo/Gen/My/yes | Ataxia, myoclonus, tremor, dystonia, parkinsonism |
| 12/M Infancy/59 y | c.110G>A, p.(Arg37His) | GDD | Mild ID, impulsivity, executive dysfunction | 19 years/Gen/GTC/no | Ataxia, myoclonus, tremor, parkinsonism, spasticity |
| 13/F 2 y/34 y | c.109C>T, p.(Arg37Cys) | DD, myoclonus, ataxia, stereotypies | Severe ID, anxiety, phobias, catatonia | Childhood/Gen/GTC/no | Myoclonus, ataxia, stereotypies |
| 14/F 2 y/34 y | c.109C>T, p.(Arg37Cys) | DD, myoclonus, ataxia, stereotypies | Severe ID, anxiety, phobias | Childhood/Gen/GTC/no | Myoclonus, ataxia, stereotypies |
| 15/M First mo/16 y | c.104G>A, p.(Gly35Glu) | craniosynostosis, GDD | Moderate ID | 3 y/Fc/partial/no | Tremor, chorea, myoclonus, dystonia, ataxia |
| 16/F NR/4 y | c.632G>A (p.Arg211GIn) | GDD, epilepsy | GDD | 21 mo/Gen/My, At, absence/no | – |
| 17/M 5 y/44 y | c.632G>A (p.Arg211GIn) | FS | Psychosis | 5 y/Gen/absence, My, GTC/no | Myoclonus, tremor, ataxia |
| 18/M 1 y/17 y | c.638G>A, p.(Ser213Asn) | DD, tremor, epilepsy | Severe ID | 1 y/Gen/absence, MA, Tn, GTC/yes | Tremor, ataxia, myoclonus, parkinsonism |
| 19/F 6 mo/18 y | c.614G>A, p.(Arg205Gln) | DD, epilepsy, tremor, myoclonus, ataxia | Mild ID, ADHD, anxiety, oppositional behaviour | 1 y/Gen/absence/no | Tremor, ataxia, dystonia, parkinsonism |
| 20/M 1 y/14 y | c.632G>A (p.Arg211GIn) | GDD, epilepsy | Moderate ID, Anxiety, autistic traits | 6 mo/Gen/absence, MA, GTC, Tn, At/yes | Tremor, ataxia, myoclonus, dystonia, parkinsonism |
| 21/M 18 mo/16 y | c.104G>A, p.(Gly35Glu) | GDD, hypotonia | Moderate ID, ASD | 11 mo/Gen/GTC, absence, My, At/yes | Ataxia, tremor, chorea, rigidity |
| 22/M 6 mo/14 y | c.632G>A, p.(Arg211Gln) | GDD, hypotonia | Severe ID | 2 y/Gen/GTC, absence/no | Ataxia, myoclonus, tremor |
| 23/F 3 mo/16 y | c.632G>A, p.(Arg211Gln) | GDD, tremor, clumsiness | Mild ID | – | Tremor |
| 24/F 7 mo/22 y | c.124_126del, p.(Lys42del) | GDD, epilepsy | Severe ID, ASD | 7 mo/Gen/FS, GTC, My, absence, At/yes | Tremor, myoclonus, parkinsonism |
| 25/M 18 mo/7 y | c.110G>A, p.(Arg37His) | GDD, epilepsy | Moderate ID, hyperactivity | 8 mo/Gen/FS, My, MA, absence/yes | Ataxia |
Detailed clinical information is provided in Supplementary Table 2 and Supplementary material as case reports. ADHD = attention-deficit/hyperactivity disorder; ASD = autism spectrum disorder; At = atonic; F = female; Fc = focal; FS = febrile seizures; Gen = generalized; GTC = generalized tonic-clonic; M = male; MA = myoclonic-atonic; Mo = months; My = myoclonic; NA = not assessed; OCD = obsessive compulsive disorder; Tn = tonic; y = year/years.
aPatient number/sex/age of onset/age at follow-up.
bEpilepsy age of onset/epilepsy type/seizure type/resistance to anti-epileptic drugs (yes/no).