Figure 2.

Clinical Features of Individuals with Mutations in CDC45

(A) Pedigrees of families segregating mutations in CDC45. Note consanguinity in families 5, 7, and 11 and that all parents and unaffected siblings available for testing were heterozygous for only one variant, consistent with autosomal-recessive inheritance.

(B) Facial appearance of individuals with CDC45 mutations. Many individuals demonstrate the facial characteristics of MGS including microtia, small mouth, full lips, and micrognathia, but there is a marked spectrum of severity across the cohort. Note the consistent appearance of thin eyebrows.

(C) CT head scans and plain skull radiographs of individuals with CDC45 mutations demonstrating premature fusion of cranial sutures. Note the discordance in suture fusion between sibs P9-1 and P9-2. Imaging of P8 indicates progressive suture closure (P8 left panel, age 2 years 4 months; P8 right panel, age 3 years 8 months). Skull radiography of P5 demonstrates a beaten-copper appearance of the skull.

(D) Individuals with CDC45 mutations have below-average stature and many exhibited intrauterine growth retardation and microcephaly (both in utero and postnatally). Abbreviations are as follows: Lgt, length; OFC, occipitofrontal circumference; Wgt, weight; Hgt, height. Blue indicates individuals derived from craniosynostosis cohort; black indicates individuals derived from MGS cohort.