Fig. 4.

Facial and limb features of individuals with HUWE1 variants, frontal and lateral views. a Facial features of all but two patients in the cohort. Patient numbers correspond to those in the text and tables. Detailed description of facial phenotype can be found in Table 1. Note the particular phenotype in P1 to P3 (carrying the same de novo c.329 G > A p.Arg110Gln variant) consisting of a flat face, prominent eyes and a small nose, compared with other patients (P4–P20) who present with deep set eyes, epicanthic folds, blepharophimosis, broad nasal tip and thin upper lip. The facial shape seems to evolve with time, from round face with full cheeks to long face, as seen in P6, P19 and P20. b Skeletal features include small hands, short distal phalanges and short nails in P1–P3, clinodactyly of 5th fingers, small nails, short metatarsals and 3rd–5th toes in P1 and P2, 2–3 syndactyly in P1 and P3. Tapering of fingers and puffy hands are shown in P8, and overlapping toes in P16 and P17. (Color figure online)