Table 1.
Clinical findings in neuropaediatric patients with homozygous FILIP1 variants
| Family A | Family B | Family C | Family D | ||
|---|---|---|---|---|---|
| Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | |
| FILIP1 variant | c.169C>T; p.[Arg57*] hmz | c.169C>T; p.[Arg57*] hmz | c.3398C>T; p.[Pro1133Leu] hmz | c.115C>T; p.[Arg384*] hmz | c.1156C>T; p.[Arg386Cys] hmz |
| Gender | Female | Female | Male | Male | Male |
| Consanguinity | Yes | Yes | Yes | Yes | Yes |
| Origin | Pakistan | Pakistan | Germany | Turkey | Syria |
| Onset | Congenital | Congenital | Congenital | Congenital | Congenital |
| First symptoms | Floppy infant, contractures | Floppy infant, contractures | Floppy infant, clubfeet | Floppy infant, contractures of hands, clubfeet, bilateral cleft lip and palate | Occipital encephalocele |
| Motor milestones | Delayed (sitting without support at 18 mo) | Delayed | Delayed (sitting without support at 42 mo) | Not achieved (last exam. at age 13 mo) | Delayed (walking at 3 y) |
| Speech development | Delayed (first words 2.5 y) | Delayed (first words 2.5 y) | Delayed (first words at 3 y) | No | Delayed (first words at 4 y) |
| Intellectual disability/learning difficulties | Yes | Yes | Yes | Yes (no development) | Yes |
| Joint hypermobility | No | No | Yes | No | No |
| Heart | Normal | Normal | Normal | ASDII, VSD | Normal |
| Muscle biopsy | Unspecific findings | Unspecific findings | Unspecific findings | Not performed | Not performed |
| Cranial MRI | No | No | No abnormalities | Semilobar holoprosencephaly | Atretic parietal encephalocele with associated minor anomalies of the cerebellar tentorium, and partial agenesis of corpus callosum |
| Epilepsy | No | No | No | Yes | No |
| EEG | No | No | No | Pathologic | Normal |
| Microcephalus | No | No | No | Yes | Borderline microcephaly (3rd centile) |
| Diabetes insipidus | No | No | No | Yes | No |
| Micropenis | N/A | N/A | No | Yes, cryptorchidism | No |
| Cleft lip/palate | No | No | No | Yes | No |
| BAEPs | N/A | N/A | Normal | No responses to an auditory stimulus (deafness) | N/A |
| Visual problems | No | No | No | Blindness | No |
| Facial dysmorphisms | Facial weakness, ptosis, high arched palate | Facial weakness, ptosis | Epicanthus, hypertelorism, | Bilateral cleft lip and palate, hypertelorism | Down slanted palpebral fissures, depressed nasal bridge |
| Others | Rough skin prone to hypertrophic scaring, frequent episodes of pneumonia, exercise induced myalgia, one hand Gower’s manoeuvre | Exercise induced myalgia, one hand Gower’s manoeuvre | Adducted thumbs | Bilateral contractures of hands and feet, small hypoplastic deep set nails, pituitary insufficiency | Occipital encephalocele, supernumerary nipple, single transverse palmer crease of the left hand |
| Birth weight, g (Perc./SD) | n.d. | n.d. | 2790 (−1.17z) | 3320 (50th) | n.d. |
| Birth length, cm (Perc./SD) | n.d. | n.d. | 48 | 48 (10th–25th) | n.d. |
| Birth OFC, cm (Perc./SD) | n.d. | n.d. | 34 | 34.5 (50th) | n.d. |
| Latest weight, kg (Perc./SD) | n.d. | n.d. | n.d. | 6.165 (<3rd, −3.5z) | 20.9 (59th) |
| Latest length, cm (Perc./SD) | n.d. | n.d. | n.d. | 66 (<3rd, −3.5z) | 117 (52nd) |
| Latest OFC, cm (Perc./SD) | n.d. | n.d. | n.d. | 41 (<3rd, −2.3z) | 49.5 (3rd) |
| Age at last clinical exam. | 15 y | 11 y | 5 y and 6 mo | 13 mo | 5 y and 9 mo |
ASDII = atrial septal defect type II; BAEPs = brainstem-evoked response audiometry; exam. = examination; mo = months; Perc. = percentile; SD = standard deviation; VSD = ventricular septal defect; y = years.