Table 1.
Clinical and Imaging features of individuals with biallelic ZNF335 variants
| CLINICAL FEATURES | |||||
|---|---|---|---|---|---|
| Family 1 | Family 2 | Family 3 | Family 4 | ||
| Reference | This report, Patient A | This report, Patient B | Sato et al., 2016 | Yang et al., 2012, Individual 8 | Yang et al., 2012, Individual 9 |
| Sex | M | M | F | M | M |
| Nucleotide variant(s) (NM_022095.3) | homozygous c.1399T>C | Compund heterozygous c.2171_2173delTCT and c.3998A>G | Compound heterozygous c.1399T>C and c.1505A>G | homozygous c.3332G>A | homozygous c.3332G>A |
| Protein sequence variations(s) | p.(Cys467Arg) | p.(Phe724del) and p.(Glu1333Gly) | p.(Cys467Arg) and p.(Tyr502Cys) | p.(Arg1111His) | p.(Arg1111His) |
| Age at examination [age at death] | 5 days [5 days] | 3 months | 33 months | 3 months [unknown] | 8 months [unknown] |
| Birth head circumference (SD) | 28.5 cm (−3.24 SD) | 36.8 cm (+0.55 SD) | 32 cm (−0.6 SD) | ND | 26.5 cm (−4.1 SD) |
| Head circumference on examination (standard deviations) | 28 cm (−3.7 SD) | 40 cm (−1.22 SD) | 41 cm (−5.1 SD) | 27.5 cm (−9 SD; −7.1 SD corrected for prematurity) | 32 cm (−9.9 SD) |
| Neurological features | Severe hypotonia | Hypertonia, spasticity | Spastic paralysis, hypertonia, moderate sensorineural hearing loss | Hypertonia, spasticity | ND |
| Epilepsy | Yes | No | Yes | Yes | Yes |
| Age at seizure onset | Birth | N/A | 3 months | Birth | ND |
| Seizure type | Focal | N/A | Afebrile seizures, partial seizures, focal | Paroxysmal myoclonic jerks | Paroxysmal myoclonic jerks |
| Refractory | Yes | N/A | No, well controlled on monotherapy | ND | ND |
| Growth and development | NA | Normal growth with mild delay in voluntary movements | Severe motor delay: no voluntary movement; language delay: absent speech | Short stature: 51 cm at 3 months (−3 SD, corrected for prematurity) | Low weight: 5.2 kg at 8 months (−4 SD) |
| Dysmorphic features | Low sloping forehead, flat occiput | Prominent nasal bridge | Low sloping forehead, micrognathia | Low sloping forehead, prominent nasal bridge, micrognathia, prominent ear helices, bilateral simian creases | ND |
| CLINICAL FEATURES | |||||
| Other | Bradycardia, apnea | Gastroesophageal reflex | Systolic murmur, ventricular septal defect, bradycardia, entropium ciliarum, gastroesophageal reflux | Twin, born at 35 weeks gestation, IUGR, choanal atresia, bilateral cataracts, bilateral flexion contractures of thumbs and hands with overriding fingers, bilateral dorsiflexion of feet with overring toes | Joint contractures |
| BRAIN IMAGING FEATURES | |||||
| Age at MRI | 4 days | 3 months | 3, 5, and 16 months | 3 months | NA |
| Subarachnoid spaces | Enlarged, most pronounced in the temporal fossa bilaterally | Normal | Enlarged | Enlarged | |
| Gyral pattern | Frontal agyria, posterior simplified gyral pattern | Normal | Progressive corticosubcortical atrophy | Markedly simplified gyral pattern | |
| White matter | Posterior limb of the internal capsule present, little to no myelinated white matter | Hypomyelination | Hypomyelination | Severely reduced white matter with delayed myelination | |
| Lateral Ventricles | Enlarged lateral ventricles, most pronounced over the occipital and hippocampal horns | Normal | Enlarged | Enlarged relative to hemispheres | |
| Corpus callosum | Thin, prominent column of the fornix | Normal | Thin | Absent | |
| Basal Ganglia | Absent | Present | Absent | Absent | |
| Thalami | Present | Present | Present | ND | |
| Hippocampus | Malformed | Present | ND | ND | |
| Brainstem | Hypoplasia | Present | Hypoplasia | Hypoplasia | |
| Cerebellar hemispheres | Hypoplasia | Present | Progressive atrophy | Hypoplasia | |
| Cerebellar vermis | Hypoplasia | Present | Progressive atrophy | Hypoplasia | |
SD standard deviations; ND not described; NA not applicable; IUGR intra-uterine growth retardation