A male infant was delivered vaginally at 37+4 weeks after an uncomplicated pregnancy with normal antenatal ultrasonography. An abnormal head shape was noted, with normal head circumference, reduced biparietal diameter, orbital hypertelorism, short philtrum and microretrognathia (figure 1A–C). The skull felt soft when palpated. The rest of physical examination was normal. An X-ray (figure 1D), MRI and three-dimensional CT scan reconstruction of the skull (figure 1E,F) showed a severe defect in ossification of the calvaria and widely enlarged sutures. A skeletal survey showed no other abnormalities. Trio whole-exome sequencing identified p.Ser124ter …