Table 1.
Clinical and genetic analysis of 13 cases in this cohort.
| Patient | P1 | P2 | P3 | P4 | P5 | P6 | P7 | P8 | P9 | P10 | P11 | P12 | P13 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Variant | c.3562C > T (p.R1188*) | c.2398_2401del (p.E800Nfs*62) | c.4911delT (p.P1638Lfs*48) | c.5659C > T (p.Q1887*) | c.1801C > T (p.R601*) | c.1903_1907del (p.K635Qfs*26) | c.1903_1907del (p.K635Qfs*26) | c.1903_1907del (p.K635Qfs*26) | c.2262dupA (p.E755Rfs*27) | c.5519C > T (p.A1840V) | c.7832A > T (p.H2611L) | c.6122T > G (p.V2041G) | c.6528_6538del (p.G2177Hfs*5) |
| Variation source | De novo | De novo | De novo | Na | De novo | De novo | Na | De novo | De novo | Mother | De novo | Father | De novo |
| Age at diagnosis | 3y4m | 1y2m | 5y10m | 3y8m | 15y3m | 7m17d | 7y8m | 3y6m | 6y4m | 12y | 3y6m | 4y8m | 7y |
| Gender | Male | Male | Male | Female | Male | Male | Female | Female | Female | Male | Female | Male | Female |
| ACMG | P | P | P | LP | P | P | P | P | P | VUS | LP | VUS | P |
| Birth history | +SGA | − | − | − | − | Na | − | − | − | − | − | +SGA | − |
| Perinatal issues | − | +Feeding difficulties | +Feeding difficulties, vomit | +Feeding difficulties, vomit | +Feeding difficulties | Na | − | +Hypotonia | +Feeding difficulties | − | Na | +Feeding difficulties, large fontanelles | − |
| Craniofacial anomalies | + | + | + | + | + | + | + | + | + | + | + | + | + |
| Dental anomalies | |||||||||||||
| Macrodontia | + | + | + | + | + | Na | + | + | − | + | + | + | Na |
| Other dental anomalies a | + | − | + | + | − | Na | + | + | + | − | Na | + | Na |
| Skeletal anomalies | |||||||||||||
| High palate | + | Na | − | + | − | + | − | − | + | − | + | + | + |
| Clinodactyly of the 5th finger | + | + | − | + | − | Na | + | + | + | − | + | + | + |
| Short finger/small hand | − | − | − | − | + | Na | + | + | + | − | − | − | − |
| scoliosis/kyphosis | − | − | − | Na | Na | Na | Na | − | − | + | − | − | + |
| Other skeletal anomalies b | + | − | + | Na | Na | Na | Na | + | – | Na | – | – | + |
| Short stature | −, 92.2 cm (−1.8 SD) | −, 77 cm (−0.6 SD) | +, 99.8 cm (−3.8 SD) | +, 91 cm (−2.7 SD) | −, 160 cm (−1.6 SD) | −, 69.5 cm (−0.2 SD) | −, 123 cm (−0.7 SD) | −, 99 cm (−0.6 SD) | −, 114 cm (−1.5 SD) | +, 132 cm (−3.2 SD) | +, 92 cm (−2 SD) | +, 101 cm (−2 SD) | −, 116.5 cm (−1.9 SD) |
| Growth retardation | |||||||||||||
| Global development delay | + | + | + | + | − | + | + | + | + | − | Na | + | + |
| Speech and language development delay | +22 mo | + | − | − | − | Na | +4 yr | − | Na | +22 mo | + | − | + |
| Intellectual disability/learning difficulties | + | + | + | − | + | + | + | +IQ79 | − | + | +IQ74 | − | + |
| Behavioural anomalies | − | − | − | +Hyperactivity | Na | Na | +Hyperactivity, short attention span | − | +Short attention span | +Hyperactivity, short attention span | +less communication | +short attention span, timid | Na |
| Delayed bone age | Na | Na | + | + | + | Na | −Advanced | − | + | + | − | Na | Na |
| Neurological abnormalities | |||||||||||||
| Epilepsy | − | − | − | − | Na | − | − | + | − | − | Na | − | − |
| EEG anomalies | Na | + | Na | Na | Na | − | Na | + | Na | Na | Na | − | Na |
| Brain imaging anomalies | Na, pituitary MRI(−) | +Left ventricle slightly wider | − | Na | +Small pituitary | Na | Na, pituitary MRI(−) | - | Na | Na, pituitary MRI(−) | Na | − | Na |
| Ocular anomalies | − | Na | − | − | +Visual field defect | Na | +Strabismus | Na | +Strabismus | − | − | +Astigmatism | +Myopia |
| Hearing loss | − | Na | − | − | + | − | − | − | + | − | Na | +Recurrent otitis media | − |
| CHD | +PDA | − | +VSD | Na | − | +VSD | +VSD | − | Na | − | − | + | − |
| Cryptorchidism | + | − | + | / | − | − | / | / | / | + | / | − | / |
| Renal anomalies | − | − | − | Na | − | Na | Na | Na | Na | Na | Na | − | Na |
| 1st degree relative with KBG | − | − | − | Na | − | − | − | − | − | − | − | − | − |
| Additional features | Deviated nasal septum, sinusitis, preauricular skin tag, supra-auricular pit | Head pilomatrixoma, large fontanelles | Inguinal hernia, micropenis | − | Delayed puberty, micropenis, small testicles, hypogonadotropic hypogonadism, enlarged vestibular aqueduct, obesity | − | Central precocious puberty | Supra-auricular pit | − | – | − | − | − |
+, Positive Phenotype; −, Negative Phenotype; Na, Data non-available; SGA, small for gestational age infant; PDA, Patent ductus arteriosus; VSD, Ventricular septal defect; ACMG, the American College of Medical Genetics and Genomics; VUS, Uncertain significance; P, Pathogenic; LP, Likely pathogenic. a, Other dental anomalies include misalignment of teeth (P1,P3,P4,P7,P8,P9,P10), oligodontia (P9), hypoplasia of dental enamel (P12). b, Other skeletal anomalies include pectus excavatum (P1), spina bifida occulta (P3), caudal appendage (P8), joint stiffness and shallow acetabular fossae (P13). Bold: represents large class.