Table 3.
Phenotypic characteristics of patients with KMT2B-related non-dystonia phenotype (n = 9)
| Pt | Variant inheritance; how diagnosed | Age, y: Sex | Presentation reason | Birth/neonatal Issues | DD/ID/ASD | Microcephaly/OFC (centile) | Weight/height (centile) | Dysmorphism | Eyes | Psychiatric | Other |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 45 |
c.1127_1130delAGGA p.Lys376Argfs*10 de novo; diagnostic WES |
4: M | GDD, feeding difficulties |
36 weeks/ DCDA twin; feeding issues |
Y/Y/N | Y/<0.4th | 25th/9th–25th | Epicanthic folds; posteriorly rotated ears; bil. 5th finger clinodactyly | N | N | Hypotonia |
| 46 |
c.3147_3160del p.Gly1050Profs*33 Unknown; identified in son (Pt17); research SS |
57: F | Son (Patient 17) with dystonia | NR | NR/Y/N | NR | NR/0.4th–2nd | Bulbous nose | N | N | N |
| 47 |
c.3325delC p.Arg1109Glufs*73 Unknown; Identified in sibling (Pt 18); diagnostic panel |
29: F | ID | Term | Y/Y | NR | 91st–98th/<0.4th | Small hand and feet | N | N | Fatty liver -improved with dietary; congenital septal defect |
| 48 |
c.3665G>A p.Cys1222Tyr de novo; research WES |
10.8: M | ID, dysmorphism | Term/feeding issues | Y/Mod/N | Y/2nd | 9th/9th | CDLS like craniofacial dysmorphism; ptosis; 2nd/3rd toe syndactyly | N | N | Cyclical vomiting; recurrent infection |
| 49 |
c.3885 G>A p.Trp1295* de novo; diagnostic WES |
11.8: F | GDD | Term/GORD. poor weight gain | Y/Y/Y | N/50th | 25th–50th/25th–50th | Bil. 5th finger clinodactyly | CVI; astigmatism; hyperopia | ADHD | Stereotypies; constipation; urinary incontinence |
| 50 |
c.4789C>T p.Arg1597Trp de novo; research WES |
12.3: F | Sev ID, partial disaccharide deficiency | IUGR; talipes; feeding issues | Y, speech delay/Sev/N | Small for age, no centiles | 25th/25th | Abnormal palmar crease; epicanthic folds; straight nose | Strabismus | Challenging behaviour | Faecal incontinence; iron def anaemia |
| 51 |
c.5046C>G p.Cys1682Trp de novo; diagnostic WES |
6.7: F | Speech delay | Term | Y, speech delay/N/N | Yes | 2nd/25th | Bil. 5th finger clinodactyly; epicanthic folds; 2nd/3rd toe syndactyly | N | ADHD | N |
| 52 |
c.6895dup p.Arg2299fs*4 de novo; diagnostic WES |
20: F | Feeding issues, ID | Feeding issues/IUGR | Y, speech delay/Mild/Y | Y/<0.2th | 2nd–9th/9th | Bil. 5th finger clinodactyly, syndactyly of 2nd and 3rd toes and clinodactyly of 4th and 5th toes Full cheeks, deep-set eyes with periorbital fullness | N | N | N |
| 53 |
c.7271dupT p.Ser2425Glnfs*3 de novo; diagnostic WES |
2.2: F | Developmental delay | IUGR, RDS, Feeding issues; FTT | Y, global/Sev/N | Y/<3rd | 0.4th/9th | Frontal bossing, retrognathia, high arched uvula and inverted nipples; Bil. 5th clinodactyly | N | N | GORD, needing Nissen’s fundoplication; hypotonia |
NM_014727.2, GRCh38 (Chr 19). ADHD = attention deficit hyperactivity disorder; ASD = autism spectrum disorders; Bil. = bilateral; CDLs = Cornelia de Lange syndrome; CVI = cortical visual impairment; DCDA = dichorionic diamniotic; DD = developmental delay; FTT = failure to thrive; GDD = global developmental delay; GORD = gastro-oesophageal reflux disease; ID = intellectual disability; IUGR = intrauterine growth restriction = Mod = moderate; RDS = respiratory distress syndrome; Sev = severe.