Table 1.
Summary of phenotypic and genetic findings.
| Findings | Family 1, II:2 | Family 1, II:4 | Family 2, II:1 | Family 3, II:1 | Family 4, II:1 | Family 5, II:1 | Family 6, II:2 | Family 6, II:4 | Family 7, II:1 |
|---|---|---|---|---|---|---|---|---|---|
| General Information | |||||||||
| Age | 25 y | 15 y | 27 y | 9 y | 29 y | 3 y | 9 y | Birth | 18 m |
| Gender | M | M | M | F | M | M | F | F | M |
| Ethnicity | Asian | Asian | White British | Mixed European Origin | Caucasian | Moroccan | Libyan | Libyan | Spanish |
| Consanguinity | No | No | No | No | No | Yes | Yes | Yes | NK |
| Genetic findings | |||||||||
| ALDH1A3 variantsa | c.874G>T, p.Asp292Tyr; c.1393A>T, p.Ile465Phe | c.874G>T, p.Asp292Tyr; c.1393A>T, p.Ile465Phe | c.845G>C, p.Gly282Ala; c.1459A>G, p.Arg487Gly | c.847_849del, p.Gly283del; c.953C>A, p.Ser318Tyr | c.566G>A, p.Trp189*; c.100-2A>G | c.1233 + 2T>C | c.1144G>A, p.Gly382Arg | c.1144G>A, p.Gly382Arg | c.434C>T, p.Ala145Val |
| Growth | |||||||||
| Birth weight (kg) | 3.45 | 2.38 | 2.77 | 3.1 | 3.2 | 3.6 | 3.3 | 3.77 | NK |
| Height (cm, centile) | 165.5, 2nd–9th (24 y) | 156, 9th (14 y) | NK | 48.5; 25th (birth) | 172; 25th (25 y) | 51; 50th (birth) | 123; 9th (9 y) | 50; 50th (birth) | NK |
| Weight (kg, centile) | 76.5, 75th–91st (24 y) | 35.6, 2nd (14 y) | NK | NK | NK | NK | 24; 9th–25th (9 y) | NK | NK |
| HC (cm, centile) | 58, 91st–98th (24 y) | 52.3, 0.4th–2nd (14 y) | NK | 32.5; 9th (birth) | 59.2; 91st–98th (25 y) | 37; 75th (birth) | 50.3; 10th (9 y) | 35.5; 91st (birth) | NK |
| Ocular | |||||||||
| Anophthalmia | Bil | Bil | Bil | – | – | – | Bil | Bil | – |
| Microphthalmia | – | – | – | Bil | Bil | Bil (L > R) | – | – | Bil |
| Coloboma | – | – | – | Bil | – | R | – | – | Bil |
| Cataract | – | – | – | – | – | R | – | – | – |
| Other | Lower lid cyst (R) | – | Ocular cyst (Bil) | RD and nodule near retina with small calcifications | – | – | – | – | Abnormal ASM |
| Craniofacial | |||||||||
| Nasal anomalies | – | – | – | – | – | – | EN | – | WNB, EN, SP |
| SPF | – | – | – | – | – | – | + | + | + |
| DCM | – | – | – | – | – | – | – | + | + |
| Other | – | – | – | – | – | – | – | – | Telecanthus, Micrognathia, EF, EP, EUL, HF, FC |
| Developmental | |||||||||
| ID | – | + | + | – | – | – | + | – | – |
| Motor Delay | – | + | + | – | – | – | + | – | – |
| Speech Delay | – | Nonverbal | + | – | – | – | – | – | – |
| Autism | – | + | Autistic features | – | – | – | – | – | – |
| MRI findings | Normal | NK | Normal | NK | Normal | NK | Rudimentary ON and chiasm | Hypoplastic ON, Bil DL | NK |
| Other findings | Fistula-in-ano | – | Seizures | – | Crowded teeth | – | – | – | – |
Variants are reported according to GRCh37/hg19.
ASM Anterior eye segment morphology, Bil Bilateral, DCM Downturned corners of mouth, DL Dysplastic lens, EF Epicanthic folds, EN Enlarged nares, EP Eyelid ptosis, EUL Everted upper lip, F Female, FC Full cheeks, HC Head circumference, HF High forehead, ID Intellectual disability, L Left, M Male, m months, NK Not known, ON Optic nerves, R Right, RD Retinal detachment, SP Short philtrum, SPF Short palpebral fissures, WNB Wide nasal bridge, y year.
a(NM_000693.4).