Fig. 2

Facial photographs of selected patients with expanding clinical features or harboring high-level candidate genes. (a–d) Two phenotypically similar patients (ID32410 and 76870) with likely pathogenic variants in mitochondria-related genes MT-ATP6 and KARS at 15 years 3 months and 16 years 2 months, respectively. Note apparently closely spaced eyes, long nose with bulbous tip, apparently narrow mouth with crowded teeth, and large chin. (e–f) Patient 74812 with P/LP biallelic variants in PLK4, aborted at gestational week 23. Note sloping forehead, upslanting palpebral fissures, retrognathia, and apparently large ears with increased posterior angulation. (g–h) Patient 68629 with biallelic variants in a high-level candidate gene TEDC1 at 5 months (g) and 5 years 8 months (h). Note apparently broad forehead at young age, facial scoliosis (asymmetry with curvatures in relation to the vertical axis of the face), mild ptosis, beaked nose, apparently short ears, and micrognathia. (i–j) Patient 60361 with a de novo variant in a high-level candidate gene ZNRF3 at 4 years 9 months. Note sparse hair, left-sided microphthalmia with the secretions around both eyes due to lacrimal duct obstruction, narrow nose and nares, apparently large protruding ears, deep philtrum, thin lip vermilion (i), and oligodontia with conically shaped teeth (j). (k–l) Patient 74091 with homozygous variants in a high-level candidate gene DDX1 at 6 months. Note round face with mildly upslanting palpebral fissures, retrognathia, and apparently large ears with increased posterior angulation. P/LP pathogenic or likely pathogenic.