Primordial dwarfism, microcephaly and global developmental delay in a child with an ASPM-related disorder from consanguineous parents

We report on a 1½-year-old girl, born to consanguineous parents of Somali origin. Severe intrauterine growth retardation had been diagnosed during pregnancy. Postnatally, she presented with short stature (length and weight <3rd percentile) and prenatal-onset severe, progressive microcephaly (head circumference was -6SD at birth and <-11SD at 3 months and -12SD at 14 months). Further dysmorphic features included micrognathia, and a high-arched palate. Additional clinical features included global developmental delay, central hypotonia, a small umbilical hernia, and a sacral hypermelanotic lesion.
Whole-exome sequencing revealed a homozygous ASPM (NM_018136.5) variant: c.637delA; p.(Ile213TyrfsTer47). This single-nucleotide deletion causes a frameshift and premature termination. According to ACMG criteria (PVS1, PM2, PP1), the variant is classified as Pathogenic.