Table 2.
Clinical features for subjects with de novo RNF2 missense variants
| Individual 1 | Individual 2 | |
|---|---|---|
| Age | 11 years | 3.5 years |
| Gender | F | F |
| RNF2 variant | NM_007212.3:c.209G>A Chr1(GRCh37):g:185060832 G>A p.(Arg70His) | NM_007212.3:c.246T>G Chr1(GRCh37):g.185060869T>G p.(Ser82Arg) |
| Prenatal | IUGR, oligohydramnios | IUGR |
| Birth parameters | Length: 48.3 cm (50%) | Length: 44.5 cm |
| Weight: 2381 g (50%) | Weight: 2330 g | |
| OFC: 29 cm (<1%) | OFC: 31.5 cm | |
| (36 weeks GA) | (39 weeks GA) | |
| Dysmorphic features | Depressed nasal bridge, arched eyebrows, deep set and hyperteloric eyes, upturned and broad nose, short philtrum, prominent lips, prominent and wide mouth, wide-spaced incisors, very small hands and feet | Almond shaped eyes with everted lower eyelid, long eyelashes, hypertelorism, smallmouth, dysplastic ears |
| Current growth parameters | Height: 141.8 cm (25th percentile) | Height: 93 cm (10-25th percentile) |
| Weight: 36.3 kg (25-50th percentile) | Weight: 13.4 kg (25th percentile) | |
| OFC: 50.4 cm (1st percentile) | OFC: 48 cm (10-25th percentile) | |
| Developmental delay/intellectual disability | Severe | Severe |
| Neurological | Seizures, hypotonia, hyperreflexia | Seizures, axial and limb hypotonia |
| Abnormal behaviors | Episodic irritability, self-injurious behaviors, severe sleep disturbance | Hand stereotypies |
| Brain imaging | Diffuse loss of white matter with normal myelination at 15 months; Abnormal white matter signal and diminished subcortical WM volume, focal T2 hypointense, T1 isointense right frontal lobe subcortical WM at 10 years | Possible delayed myelination at 3 months; normal at 12 months |
| Ophthalmologic | Strabismus, exotropia, astigmatism | Strabismus, exotropia |
| GI/Feeding | Feeding difficulties and failure to thrive requiring gastrostomy at 21 months, omphalomesenteric duct cyst | Feeding difficulties with persistent dysphagia, gastrointestinal dysmotility and reflux |
| Other | Very small ear canals, frequent ear infections, mild tricuspid regurgitation, pilomatrixomas on cheek and ear | Umbilical hernia |