Table 1.
Genetic and phenotypic features of patients with CASP2 variants and literature review of patients with CRADD and PIDD1-associated diagnoses.
| Subjects with CASP2 variants | Subjects with PIDD1 variants | Subjects with CRADD variants | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Family 1 (II-3) | Family 2 (II-1) | Family 3(II-1,II-2) and 4 (II-1,II-2) | Family 5 (II-1) | Total | Zaki et al. [9] | Sheikh et al. [27] | Harripaul et al. [8] | Hu et al. [32] | Total | Koprulu et al. [28] | Polla et al. [30] | Harel et al. 2016 | Di Donato et al. [7] and Avela et al. [31] | Total | |
| Self-reported ethnicity/country of origin | Turkish | French | Iran | Iran | Egyptian (3), Pakistani, Palestinian, Colombian | Indian | Pakistani (9) | Iran (5) | Pakistani | Finland | Jewish Bukharan | Turkish, Finland, Western Europe, Mennonite | |||
| CASP2 variant (NM_032982.4) or variant type (PIDD1 and CRADD) | c.1156delT (p.Tyr386ThrfsTer25) | c.[130 C > T];[876 + 1 G > T] | c.1174 C > T (p.Gln392Ter) | c.1174 C > T (p.Gln392Ter) | Missense, nonsense, frameshift | Nonsense | Nonsense | Splice, missense | Missense | Missense | Frameshift | Missense, microdeletion | |||
| Clinical features | |||||||||||||||
| Intellectual disability / developmental delay | Mild ID | Global developmental delay, moderate ID | ID | Developmental delay | 7/7 | 11/11 | 1/1 | 9/9 | 5/5 | 26/26 | 3/3 | 22/22 | 2/2 | 13/13 | 40/40 |
| Autistic features | - | + | N/A | - | 1/3 | 4/10 | 0/1 | 0/9 | 0/5 | 4/25 | N/A | 0/22 | 0/2 | N/A | 0/24 |
| ADHD | + | - | N/A | - | 1/3 | 6/10 | 1/1 | 2/9 | 0/5 | 9/25 | 3/3 | 7/22 | 0/2 | N/A | 10/27 |
| Aggressive behavior | - | + | N/A | - | 1/2 | 9/10 | 0/1 | 4/9 | 0/5 | 13/25 | 3/3 | 10/22 | 0/2 | N/A | 13/27 |
| Other behaviors | - | Intolerance to frustration, poor social skills | N/A | - | 1/3 | 5/11 | 1/1 | 3/9 | 3/5 | 12/26 | 3/3 | 4/13 | 0/2 | N/A | 7/18 |
| Seizure | - | - | N/A | + | 1/3 | 4/11 | 1/1 | 1/9 | 3/5 | 9/26 | 0/3 | 2/22 | 0/2 | 4/13 | 6/40 |
| Neurological exam | - | Hypotonia, weakness, spasticity, and hyperreflexia | N/A | Hypotonia, poor vision, bilateral optic atrophy and abnormal uncoordinated gait | 2/3 | Hypotonia, strabismus, brisk DTR, mild gait instability, mild tremor | Normal | Bradychynesia, Strabismus | Normal | 14/26 | Strabismus | Strabismus | N/A | Normal | 2/38 |
| Dysmorphic features | Synophrys, laterally flared thick eyebrows, upslanting palpebral fissures, prominent nasal tip, thin upper lip, chin dimple, low-set, posteriorly rotated ears, and thin ear helix | - | N/A | - | 1/3 | 11/11 | 1/1 | 1/9 | 2/5 | 15/26 | 3/3 | 2/22 | 0/2 | 0/13 | 5/40 |
| Cranial MRI abnormality | |||||||||||||||
| Lissencephaly (LIS) | Bilateral pachygyria and mild cortical thickening in the fronto-temporal lobes | Bilateral pachygyria and mild cortical thickening in the fronto-temporal lobes | N/A | Bilateral pachygyria and mild cortical thickening in the fronto-temporal lobes | 3/3 | 10/10 | 1/1 | 9/9 | N/A | 20/20 | 3/3 | 17/17 | 3/3 | 13/13 | 36/36 |
| Thin corpus callosum | - | - | N/A | - | 0/3 | 5/10 | 1/1 | 1/9 | N/A | 7/20 | 0/3 | 0/17 | 0/3 | 2/13 | 2/36 |
| Other brain MRI findings | Prominent subcortical perivascular space | - | N/A | Hydrocephaly | 2/3 | 6/10 | 1/1 | 0/9 | N/A | 7/20 | 3/3 | 8/17 | 1/3 | 2/13 | 14/36 |