Table 1.
Clinical history and findings in four patients with putative ATCB loss‐of‐function variants
| Patient | Sex | Age (years) | Prenatal and neonatal history, birth measures | Postnatal growth retardation | Microcephaly | Motor delay | Speech delay | Intellectual disability | Behavioral, psychiatric and neurological features | Facial gestalt | Malformation and physical anomalies | ACTB Variant | Inheritance |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | M | 11 | Normal 40 weeks 2,900 g 48 cm 33 cm | N (3rd‐10th centile) | N (10th‐25th centile) | Y | Y | None | Attention deficit, seizures at age 5 years, additional paternally inherited axonal neuropathy | Wavy interrupted eyebrows, dense eyelashes, wide nose, wide mouth, prominent cheeks and chin | Anisometropia, unilateral high‐grade hyperopia and astigmatism | Complete heterozygous ACTB gene deletion | Maternal (son of patient 2) |
| 2 | F | 35 | SGA 40 weeks 2,120 g | N (25th centile) | N (25th centile) | N | N | None | None | Sparse scalp hair, wavy interrupted eyebrows, dense eyelashes, wide nose, wide mouth, prominent cheeks and chin | Hyperopia | Complete heterozygous ACTB gene deletion | Unknown |
| 3 | M | 4 | Normal At term 3,350 g 54 cm Slow neonatal weight gain | N (10th‐25th centile) | N (10th‐25th centile) | Y | Y | None | Autism, staring spells with normal EEG, possible attention deficit and impulse control disorder | Sparse scalp hair, deeply set eyes with prominent brow ridge, broad nasal tip, pointed chin, large prominent ears | Long toes with 2nd and 5th toe clinodactyly, sagittal craniosynostosis, hypospadias, patent ductus arteriosus | Heterozygous c.890_891delCA; p.Thr297Serfs*37 | De novo? – no access to paternal sample |
| 4 | M | 6 | Normal 40 weeks 2950 g 49 cm | N (25th‐50th centile) | N (3rd‐10th centile) | Y | Y | Mild, WISC: FSIQ 66 | Attention deficit, visuospatial deficits, speech delay | Thin hair, deep set eyes, wide nose, deep set columella | Strabismus, myopia |
Heterozygous c.905G>C; p.(Gly302Ala) MutationTaster: pathogenic (0.999; range 0–1) CADD score: pathogenic (24.0; range 0–100) PolyPhen2: benign (0.281; range 0–1) Provean: deleterious (−4.177, range ‐40–12.5, cutoff:<−2.5) |
De novo |
Abbreviations: CADD, combined annotation dependent depletion; F, female; FSIQ, full scale intelligence quotient; ID, intellectual disability; M, male; N, no or none known; SGA, small for gestational age; U, unknown; WISC, Wechsler intelligence scale for children; Y, yes; y, years.