Table 1.
Main Clinical Features of Affected Individuals
|
Individual |
Total | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | ||
| General Information | |||||||||||||||
| Age | 14 y | 5 y | 5 y | 2 y | 5 y | 10 y | 9 y, 9 m | 21 y | 16 y | 6 y | 18 y | 15 y | 7 y | 7 y | 2–21 y |
| Gender | F | M | F | M | M | M | M | M | F | F | M | F | F | F | 7 M, 6 F |
| Mutation | c.1221T>A (p.Cys407∗) | c.1216del (p.Thr406Profs∗3) | c.1260+1dup (p.Ser421Thrfs∗12) | c.1210C>T (p.Gln404∗) | c.1269_1270dup (p.Glu424Glyfs∗8) | c.1339G>T (p.Glu447∗) | c.1188_1191del (p.Asp397Alafs∗11) | c.1250dup (p.Pro418Thrfs∗16) | c.1270dup (p.Glu424Glyfs∗10) | c.1270dup (p.Glu424Glyfs∗10) | c.1281G>A (p.Trp427∗) | c.1281G>A (p.Trp427∗) | c.1654C>T (p.Arg552∗) | c.1404_1411del (p.Lys469Argfs∗4) | NA |
| Inheritance | de novo | de novo | de novo | de novo | de novo | de novo | de novo | de novo | de novo | de novo | de novo | de novo | NKa | de novo | NA |
| Growth | |||||||||||||||
| Birthweight (g) | 2,780 | 4,000 | 2,655 | 3,742 | 3,527 | 3,180 | 2,200 | 2,211 | 3,061 | 2,730 | 3,200 | 3,429 | NK | 3,140 | NA |
| Height (SD) | −2.7 | −1.5 | −2.8 | 0 | NK | −3 | <−3 | <−2.5 | −2.3 | −2.5 | −2.7 | +0.41 | −2.6 | −2 | NA |
| Weight (SD) | +2.3 | +0.5 | −1.9 | 0 | NK | +2 | +0.5 | <−2.5 | −2.2 | −2 | −1.8 | >+2.5 | −4.9 | 0 | NA |
| Head circumference (SD) | +0.7 | −0.5 | −1.5 | −0.5 | −0.5 | −1 | −1.8 | <−2.5 | −3.1 | −2.5 | −2.5 | +3.49 | NK | −1.5 | NA |
| Neurological | |||||||||||||||
| ID (severity) | + (mild to moderate) | + (mild to moderate) | + (mild) | + | + | −b | + (mild to moderate) | + (mild to moderate) | + (severe) | + (moderate) | + (moderate) | + (severe) | + (severe) | + (mild) | 13/14 (93%) |
| Hypotonia | + | + | + | + | + | − | − | + | + | + | + | − | + | − | 10/14 (71%) |
| Broad-based gait | + | NK | + | + | + | − | − | − | + | NK | NK | − | NK | − | 5/10 (50%) |
| Sensitivity to sounds | NK | NK | + | + | NK | NK | + | + | + | + | NK | NK | NK | + | 7/7 (100%) |
| Behavioral features | ADHD, ODD, anxiety disorder | sensory integration problems | short attention, panic attacks | sensory integration problems, hyperarousal, short attention | − | anxiety disorder, attention difficulties, biting | sensory integration problems, anxiety, short attention | anxiety | ASD | − | − | ASD, attention problems, oppositional, aggression | ASD | ASD | 11/14 (79%) |
| Facial | |||||||||||||||
| Broad forehead | + | + | − | − | NK | − | − | + | + | + | + | NK | + | + | 8/12 (67%) |
| Low-set, posteriorly rotated ears | + | + | + | + (right) | NK | NK | − | − | + | + | + | NK | NK | + (only posteriorly rotated) | 8/10 (80%) |
| Upturned nose | + | − | + | − | NK | − | − | − | − | + | + | NK | + | − | 5/12 (42%) |
| Thin upper lip | − | + | + | + | NK | + | − | + | + | + | + | NK | + | + | 10/12 83% |
| Broad mouth | + | + | + | − | NK | + | − | − | + | − | + | NK | − | − | 6/12 50% |
| Gastrointestinal | |||||||||||||||
| Feeding difficulty | + (neonatal) | + (neonatal) | + (neonatal) | + | + | − | + | + | − | − | + | − | + | + (neonatal) | 10/14 (71%) |
| GER and/or vomiting | + | + | + | + | NK | + | + | + (infancy) | + | + | − | − | + | − | 10/13 (77%) |
| Constipation | − | + | − | + | + | − | + | + (infancy) | + | − | NK | − | + | + | 8/13 (55%) |
| Skeletal | |||||||||||||||
| Small hands | NK | + | + | − | NK | + | + | + | + | + | + | NK | + | + | 10/11 (91%) |
| Small feet | NK | NK | + | − | NK | NK | + | + | + | NK | + | NK | + | + | 7/8 (88%) |
| Hyperlordosis | + | − | − | − | + | NK | + | + | + | NK | + | NK | NK | + | 7/10 (70%) |
| Other | |||||||||||||||
| Periodic illnessc | + | + | − | − | + | + | + | + | + | + | − | − | NK | − | 8/13 (62%) |
| High pain threshold | NK | + | + | + | NK | + | + | + | + | + | + | NK | NK | − | 9/10 (90%) |
| Congenital abnormalities | bicuspid aortic valve | retractile testes, small genital | small VSD and small ODA | − | bilateral cryptor-chidism | − | − | − | − | laryngo-malacia | − | − | bilateral parietal foramina, exostoses, diaphragmatic hernia, volvulus intestined | − | 6/14 (43%) |
| Vision problems | myopia, nystagmus, amblyopia | hyper-metropia, cilinder, strabismus | hyper-metropia | myopia, strabismus, astigmatism, CVI | − | − | hyper-metropia, strabismus, astigmatism, nystagmus | myopia, strabismus | − | hyper-metropia, strabismus | hyper-metropia, strabismus | − | strabismus, nystagmus, iridocyclitis, retinal detachment | − | 9/14 (64%) |
| Hypoplastic nails | + (toenails) | + (toenails) | + (toenails) | − | + (toenails) | − | − | + (fifth toenails) | − | − | + | NK | NK | − | 6/12 (50%) |
| Recurrent infections | − | − | NK | − | NK | NK | + | NK | + | NK | + | + | + | − | 5/9 (56%) |
Abbreviations are as follows: +, present; −, absent; y, years; m, months; M, male; F, female; NK, not known; ID, intellectual disability; ADHD, attention deficit hyperactivity disorder; ODD, oppositional defiant disorder; ASD, autism spectrum disorder; GER, gastro esophageal reflux; VSD, ventricle septum defect; ODA, open ductus arteriosus; and CVI, cerebral visual impairment.
a
Parental DNA not available.
b
Individual did have learning difficulties.
c
Including cyclic vomiting.
d
Individual 13 also had a confirmed diagnosis of Potocki-Shaffer syndrome.