TABLE 2.
Detailed clinical and molecular characteristics of 25 Korean patients with RSTS
| Patient | C‐01 | C‐02 | C‐03 | C‐04 | C‐05 | C‐06 | C‐07 | C‐08 | C‐09 |
|---|---|---|---|---|---|---|---|---|---|
| Chief complaint | DD | Multiple anomaly | Multiple anomaly | DD | DD | DD | DD | DD | DD |
| Sex (M:F) | M | F | M | M | F | M | M | M | F |
| Maternal preeclampsia | − | − | − | − | − | − | |||
| NICU care | + | + | − | + | − | − | |||
| Growth profile | |||||||||
| Short stature at diagnosis | + | + | + | − | − | + | + | − | |
| Microcephaly at diagnosis | + | + | + | + | + | − | + | − | |
| Short stature at last follow‐up | + | + | + | + | − | − | |||
| Obesity a at last follow‐up | − | + | − | − | + | − | |||
| Clinical phenotype | |||||||||
| Hypertrichosis | + | + | + | + | + | + | + | + | |
| Low ant hairline | + | + | + | + | + | + | + | ||
| Arched eyebrows | + | + | + | + | + | + | + | + | |
| Long eyelashes | + | + | + | + | + | + | + | ||
| Narrow forehead | + | + | + | + | + | + | + | ||
| Convex nasal ridge | + | + | + | + | + | + | + | ||
| Large nose | + | + | + | + | |||||
| Columella below alae nasi | + | + | + | + | + | + | + | + | |
| High arched palate | + | + | + | + | + | + | |||
| Micrognathia | − | + | + | + | + | + | |||
| Low‐set ears | + | + | |||||||
| Broad thumbs | + | + | + | + | + | + | + | + | |
| Angulated thumbs | + | − | + | − | − | − | |||
| Broad halluces | + | + | + | + | + | + | + | + | |
| Polydactyly | − | + | − | + | − | − | − | − | + |
| Strabismus | +, BIO myectomy | +, BIO myectomy | + | +, BIO myectomy | +, BIO myectomy | − | +, BIO myectomy | − | + |
| Other eye problem | − |
+, glaucoma‐like disc |
+, ONLD | − |
+, optic disc coloboma |
− | − | − | − |
| Congenital heart defect | − | − | +, ASD | +, PDA | − | − | − | +, PDA | − |
| Genitourinary problem | − | − |
+, VUR grade 4, cryptorchidism orchipexy |
+, cryptorchidism orchipexy |
− | +, micropenis |
+, cryptorchidism orchipexy |
− | − |
| Gastrointestinal problem | +, GER | +, GER | +, GER | +, GER | − | − | − | − | + |
| Scoliosis | − | − | + | − | − | − | − | − | − |
| Other bone problem | − | − | − | − | − | − | − | +, funnel chest | − |
| Seizure | − | − | − | − | − | − | − | − | + |
| CNS abnormality | − | − | +, tethered cord syndrome | − | +, Suspected posterior PVWM volume loss | − | +, Chiari malformation type I | +, delayed myelination | − |
| Keloid | − | − | + | − | − | − | − | − | − |
| Malignant tumor | +, ALL | − | − | − | − | − | − | − | − |
| Intellectual disability, IQ | + | + | + | + | + | +, 40 | +, 47 | + | + |
| Age at walk alone (month) | 21 | 27 | 24 | 27 | 32 | 40 | 20 | ||
| Autism | − | − | − | − | − | + | − | + | − |
| Aggressive behavior | − | − | − | − | − | − | − | − | − |
| Genetic background | |||||||||
| Causative gene | CREBBP | CREBBP | CREBBP | CREBBP | CREBBP | CREBBP | CREBBP | CREBBP | CREBBP |
| Variant type | Frameshift | Frameshift | Frameshift | intragenic large deletion | Frameshift | Frameshift | Frameshift | intragenic large deletion | nonsense |
| Exon | exon 13 | exon 3 | exon 8 | exon 25 | exon 31 | exon 30 | exon 16 | ||
| Coding sequence c | c.2469_2470del | c.955_961del | c.1712_1716del | c.4189_4192del | c.5948del | c.4944dup | c.3121C>T | ||
| Protein‐based sequence d | p.Gln823Hisfs*8 | p.Val319Thrfs*33 | p.Ile571Asnfs*13 | p.Phe1397Leufs*61 | p.Pro1983Glnfs*16 | p.Pro1983Glnfs*16 | p.Gln1041* | ||
| Exonic deletion | exon 6–31 del | exon 6–31 del |
| C‐10 | C‐11 | C‐12 | C‐13 | C‐14 | C‐15 | C‐16 | E‐01 | E‐02 | E‐03 | E‐04 |
|---|---|---|---|---|---|---|---|---|---|---|
| DD | DD | DD | Dysmorphic face | DD | Seizure, known CP | Dysmorphic face | DD | Dysmorphic face | DD | DD |
| F | M | F | M | M | F | M | F | M | M | M |
| − | − | − | − | − | − | − | + | − | ||
| − | − | + | + | + | − | + | − | − | ||
| + | − | + | + | + | + | + | + | |||
| + | + | − | + | + | ||||||
| + | + | + | + | + | + | + | ||||
| − | − | − | − | − | − | + | ||||
| + | + | + | + | + | + | b | + | + | + | |
| + | + | + | + | + | + | |||||
| + | + | + | + | + | + | + | ||||
| + | + | + | + | + | + | |||||
| + | + | + | + | + | + | |||||
| + | + | + | + | + | + | |||||
| + | + | − | + | + | ||||||
| + | + | + | + | + | − | + | ||||
| + | + | + | ||||||||
| + | + | + | ||||||||
| + | − | |||||||||
| + | + | + | + | + | + | + | + | + | ||
| − | − | − | + | − | ||||||
| + | + | + | + | + | + | + | + | |||
| − | − | + | − | − | + | − | − | − | ||
| − | − | − | − | − | − | − | − | − | − | − |
| − | − | − | − | − | − | − | − | +, visual impairment | +, ptosis | |
| − | +, ASD | +, ASD | + | − | − | +, PDA | − | − | − | − |
| − | +, Orchiopexy | − | + Orchiopexy, micropenis | +, Orchiopexy | − | − | − | − | − | + |
| − | + | + | − | − | − | + | + | − | − | |
| − | − | − | − | + | − | − | − | + | − | − |
| +, Anterior wedging of T11‐12 spine | +, left coronal synostosis | +, dislocation of radial head | − | − | ||||||
| − | − | − | − | − | + | − | − | − | − | − |
| − | − | − | − | +, arachnoid cyst | +, Chiari I malformation | − | − | +, Tethered cord syndrome | +, Moyamoya disease | +, inferior vermian hypoplasia |
| − | − | − | − | − | − | − | − | − | − | − |
| − | − | − | − | − | − | − | − | − | − | − |
| +, 34 | + | + | + | + | +, 34 | + | + | + | +, 52 | +, 51 |
| 42 | 24 | 24 | 48 | 26 | 14 | 15 | ||||
| − | − | − | − | − | − | − | − | − | − | + |
| − | − | − | ‐ | + | − | − | − | − | + | − |
| CREBBP | CREBBP | CREBBP | CREBBP | CREBBP | CREBBP | CREBBP | EP300 | EP300 | EP300 | EP300 |
| Intragenic large deletion | Nonsense | Intragenic large deletion | Intragenic large deletion | Frameshift | Frameshift | Intragenic large deletion | Splicing variant | Frameshift | Frameshift | Frameshift |
| Exon 17 | Exon 27 | Exon 27 | Intron 24 | Exon 27 | Exon 5 | Exon 14 | ||||
| c.3307C<T | c.4400_4401del | c.4482dup | c.4173‐2A>G | c.4384C>T | c.1179_1180del | c.2520del | ||||
| p.Arg1103* | p.Val1467Aspfs*11 | p.Lys1495Glnfs*24 | Exon 25 skipping | p.Arg1462* | p.Ala394Ilefs*16 | p.Thr841Profs*9 | ||||
| Exon 1 del | Exon 6–31 del | Exon 1–3 del | Exon 17–31 del |
| U‐01 | U‐02 | U‐03 | U‐04 | U‐05 |
|---|---|---|---|---|
| Keloid | DD | DD | ||
| F | M | F | M | M |
| − | − | − | ||
| + | − | − | ||
| − | + | |||
| + | + | + | + | |
| + | − | − | ||
| − | − | + | − | |
| + | + | |||
| + | ||||
| + | − | |||
| + | ||||
| + | ||||
| + | ||||
| + | ||||
| + | ||||
| + | + | + | ||
| + | ||||
| + | + | |||
| − | − | + | ||
| − | − | + | ||
| +, Congenital glaucoma | +, ONLD | +, Epiblepharon | +, Secondary glaucoma, coloboma, | |
| − | + | − | − | + |
| − | +, Orchiopexy | − | +, Orchiopexy | +, VUR |
| − | − | + | ||
| − | − | − | − | |
| − | − | − | ||
| − | − | − | − | + |
| − | − | − | − | |
| + | − | − | − | + |
| − | − | − | − | − |
| − | + | +, 53 | +, 46 | + |
| 21 | 23 | |||
| − | − | − | ||
| − | − | − | − | |
| UN | UN | UN | UN | UN |
Abbreviations: ALL, acute lymphoblastic leukemia; ASD, atrial septal defect; BIO myectomy, bilateral inferior oblique myectomy; DD, developmental delay; GER, gastroesophageal reflux; IQ, intelligence quotient; ONLD, obstruction of the nasolacrimal duct; PDA, patent ductus arteriosus; UN, unknown; VUR, vesicourinary reflux.
a
Body mass index ≥95th percentile for children or ≥25.0 kg/m2 for adults.
b
Typical face, but no detailed medical records.
c
References for coding sequences are NM_004380.3 for CREBBP and NM_001429.4 for EP300.
d
References for protein‐based sequences are NP_004371.2 for CREBBP and NP_001420.2 for EP300.