Table 1. Summarized clinical findings.
F: female; M: male; m: months; y: years; UK: unknown; NA: non applicable; NH: neonatal hypotonia; DMM: Delayed motor milestones; RF: respiratory failure; WCB: wheelchair-bound; CPAP: Continuous Positive Airway Pressure; DCM: Dilated cardiomyopathy; LVEF: Left ventricular ejection fraction; FH: follicular hyperkeratosis; LL: lower limbs; #Proband BOS1248–1 in The Manton Center for Orphan Disease Research database.
| Family Patient Gender | Family A III.2 F | Family B III.1, M III.2, F | Family C# III.7 M | Family D II.2 M | Family E II.4 M | Family F (Davignon et al, 2016) 1F, 3M |
|---|---|---|---|---|---|---|
| TRIP4 Pathogenic variant | c.141_142delAT (p.Tyr48fs*3) homozygous | c.534C>G (p. His178Gln) + c.1544_1547del ACTG (p.Asp515fs*34) | c.1065delC (p.Ile356fs*6) homozygous | c.55_56insCT (p.Gln19fs*47) + c.1197delA (p.Ser399fs*12) | Homozygous deletion of exons 8 and 9 | c.890G>A (p.Trp297*) homozygous |
| First signs | Hypotonia, DMM | DMM (gait acquisition) in both siblings Waddling gait and fatigability in III.2 | NH, respiratory distress, feeding difficulties | NH, DMM | Difficulty running, poor sports performance (adolescence) | NH, Respiratory distress (n=3), feeding difficulties (n=3) |
| Best motor performance | Present age (9y): waddling gait, climb stairs, bipodal jump, starts to run | Present age (22y,III.1) and 16y (III.2): waddling gait, climb stairs | NA | Present age (35y): independent ambulation (short distances) | Adulthood: independent ambulation, climb stairs | Supported indoors ambulation in mildest patient until 11y |
| Evolution of motor performance | Improving | Stable | NA | Stable | Stable | WCB before adulthood |
| Scoliosis | Yes (early childhood) | Yes (early childhood) | No | Yes (early childhood) + Arthrodesis at 16y | No | Progressive scoliosis and arthrodesis in 3 |
| Rigid spine | No | Yes in III.2 | No | Yes | Yes | Yes (n=2) |
| Respiratory involvement | Respiratory infections since 7m. Nocturnal non-invasive ventilation since age 3y | Restrictive RF since childhood. Latest FVC 60% (III.1, 22y) and 52% (III.2, 18y). No assisted ventilation. | From birth. Neonatal respiratory distress needing tracheostomy and ventilation. Died from RF at 8m | Restrictive RF. Nocturnal non-invasive ventilation since 18y. Latest FVC 35% (35y) | Latest FVC 80% (63y). Obstructive sleep apnea syndrome treated by CPAP | From birth (n=3) and from 2y(n=1). Ventilation in the 1st year of life in 3 and from 11y in the mildest |
| Cardiac involvement | No | No | No | No | DCM (LVEF 25%) in the 5th decade | DCM in the 3rd decade (n=1) |
| Joint contractures | Yes (Achilles) | No | No | Yes (elbows, achilles). Joint hyperlaxity LL | Yes (elbow, mild) | Yes (n=2); Hyperlaxity (n=4) |
| Skin involvement | No | No | Yes (hyperelasticity) | Yes (hyperelasticity, FH) | Yes (xerosis, FH) | Yes (hyperelasticity, xerosis, FH) |
| Dysmorphic features | Flat face, retrognathia | No | Flat face, prominent venous markings, tapering fingers | Elongated face, low-set ears, retrognathia. Flat thorax, pectus excavatum. | Flat face, retrognathia. Flat thorax, pectus excavatum. | Flat face (n=2), flat thorax (n=3), funnel thorax (n=1), pectus excavatum (n=2), valgus feet (n=2), high arched palate (n=1) |
| Other features | Underweight (<P3) Learning and writing Difficulties | Right-eye keratoconus (III.1) Underweight (<P4) (III.2) |
Severe ophthalmoplegia | Underweight (<P3). Myopia | Mild ophthalmo-paresis. Myopia | LL lipodystrophy (n=2), learning difficulties (n=2), language delay(n=1), testicular ectopia and delayed puberty (n=1) |