Figure 1.

Presentation of disease features found in our cohort FILIP1-patients defining the congenital syndrome. (A) Female Patient 1 from Family A with homozygous p.[Arg57*] FILIP1 variants. Clinical findings include neck webbing, rigid spine, kyphoscoliosis, elbow and knee flexion contractures and bilateral foot pronation as well as flexion contractures of the fingers (i–iv). Dysmorphic features include large forehead with prominent ridging of the metopic suture, large prominent ears, prominent nose and micrognathia, ptosis, myopathic face (iii and iv). Photographs were taken at the age of 9 years. (B) Male index patient from Family B with homozygous p.[Pro1133Leu] FILIP1 variants. B(i) shows the patient as a floppy baby with congenital clubfeet and adducted thumbs and joint hyperlaxity is shown in ii. B(iii) shows the patient as a toddler (able to sit without support) presenting with ptosis, epicanthus, down-slanted palpebral fissures, hypertelorism, broad root of the nose/depressed nasal bridge. B(iv) shows severe scoliosis found in this patient. Photographs/images were taken at the age of 4 months (i), 2.5 years (ii) and 3.5 years (iii and iv). (C) shows a lobar holoprosencephaly with agenesis of corpus callosum (indicated by arrows) in Patient 4 from Family C. MRI was carried out at the age of 14 days. (C) shows Patient 5 from Family D presenting with protruding ears, ptosis, epicanthus, down-slanted palpebral fissures, hypertelorism, broad root of the nose/depressed nasal bridge (i and ii). Foot abnormalities are not present (iii). D(iv) shows residual material of an occipital encephalocele. D(v and vi) show single transverse palmar crease on the left hand, but otherwise absence of major anomalies. Photographs were taken at the age of 5 years and 9 months.