Table II.
Patient ID (DECIPHER ID) | 1 (258995) | 2 (260453) | 3 (265865) | 4 (268390) | 5 (277603) | 6 (263453) | 7 | Total (of features reported) |
---|---|---|---|---|---|---|---|---|
Genotype | c.1626_1627insA | c.418G>A | c.1117+1G>A | c.23del | c.1424_1425insTC | c.960G>A | c.1664del | - |
Protein change (predicted) | p.(Lys543*) | p.(Glu140Lys) | splice donor variant | p.(Val8Glufs*4) | p.(Ile476Profs*7) | p.(Trp320*) | p.(Leu555Argfs*51) | - |
Inheritance | De novo | De novo | De novo | De novo | De novo | De novo | De novo | - |
Additional genetic finding | n/a | Complete UPD (mat) chr 9 | n/a | n/a | n/a | n/a | n/a | - |
Age last assessed | 15yr | 14yr | 12yr | 6yr | 21yr | 11yr | 8.5yr | - |
Sex | F | M | F | F | F | F | F | - |
Pregnancy | NAD | Congenital cardiac disease 20 week scan | Maternal renal infection 16 weeks gestation | NAD | NAD | NAD | Ovarian stimulation, dizygotic twins | - |
Birth | Emergency caesarean section | NAD | NAD | NAD | NAD | NAD | NAD | - |
Neonatal unit | n/a | 18 days | n/a | n/a | n/a | n/a | Yes | - |
Gestation (weeks) | 38 | 37 | 40 | 38 | 40 | 42 | 38 | - |
Feeding Difficulties | No | Yes | No | No | No | No | No | - |
Additional
cranio-facial features |
Synophrys, deepset eyes, long eyelashes, slightly coarse | Pointed chin | Low anterior hairline, synophrys, strabismus, short upturned nose, coarse | Epicanthic folds, low set posteriorly rotated ears, upturned nose, smooth philtrum | Hypertelorism | Thick hair, prognathism | n/a | - |
Other features | Puffy dry skin over hands and feet, wide based gait | Transposition of the great vessels, tricuspid atresia, VSD. Left single palmar crease | Spinal lordosis | Bilateral 2–3 toe cutaneous syndactyly, hypermobility. | Brachydactyly, tapering fingers | Broad thumbs and great toes, truncal obesity | n/a | - |
Prominent eyebrows | No | Yes | Yes | No | Yes | Yes | No | 4/7 (57%) |
Elongated PF | No | Yes | No | Yes | Yes | Yes | No | 4/7 (57%) |
Prominent nasal bridge | No | Yes | No | No | Yes | Yes | No | 3/7 (43%) |
Overhanging columella | No | Yes | No | Yes | Yes | Yes | No | 4/7 (57%) |
Thin upper lip | Yes | Yes | No | Yes | Yes | Yes | Yes | 6/7 (86%) |
Patient ID (DECIPHER ID) | 1 (258995) | 2 (260453) | 3 (265865) | 4 (268390) | 5 (277603) | 6 (263453) | 7 | Total (of features reported) |
ID | Moderate | Moderate | Moderate | Severe | Severe | Severe | Moderate | 7/7 (100%) |
Seizures | Yes | None | Yes | Single seizure only | Yes | Yes | Yes | 5/7 (71%) |
Age onset of seizures | 5yr | n/a | 1yrr | 5yr | <1yr | 8 months | 18 months | n/a |
Febrile seizures | Yes | No | Yes | No | Yes | No | Yes | 4/7 (57%) |
EE | No | No | No | No | No | No | No | 0/7 (0%) |
Delayed development | Yes | Yes | Yes | Yes | Yes | Yes | Yes | 7/7 (100%) |
Sat independently | 9 months | 10 months | 18 months | 2–2.5yr | 15 months | 15 months | 18 months | n/a |
Walked independently | 2–2.5yr | 2–2.5yr | 4–5yr | 5yr | 22 months | 39 months | 6.5yr | n/a |
First words | Over 5yr | 2–2.5yr | 18 months | 5yr | 2–2.5yr | not achieved aged 11 yr | 3yr | n/a |
Behaviour | n/a | Angers easily, Tourette syndrome | Autism traits | Very sociable | Aggression with violent episodes | Very sociable | n/a | n/a |
Hand flapping | Yes | No | Yes | Yes | Yes | Yes | No | 5/7 (71%) |
Special educational needs | Yes | Yes | Yes | Yes | Yes | Yes | Mainstream school with additional support | 6/7 (86%) |
Cranial MRI abnormal* | No | Yes* | No | No | No | n/a | Yes* | 2/7 (29%) |
Abbreviations: EE – epileptic encephalopathy. ID – intellectual disability. n/a- not applicable. NAD- no abnormalities detected. n/r- not reported. PF – palpebral fissures. UPD- uniparental disomy. VSD – ventricular septal defect.
MRI abnormalities: Patient 2 - Small periventricular areas with high T2 signal; Patient 7 - Non-progressive T2 and FLAIR hyperintensities in white matter bilaterally.