Individuals described to date with Shashi Pena syndrome (SPS) have truncating variants in the ASLX2 gene. The variants are de novo and affect one copy of the ASXL2 gene. Mode of inheritance is autosomal dominant and mechanism of disease is unclear, but current evidence suggests dominant negative or gain-of-function. The main clinical features are macrocephaly, hypotonia, intellectual or developmental disability of varying degree, and characteristic facial features that include a glabellar nevus flammeus, prominent eyes, and hypertelorism.
ASXL2