Strømme syndrome: the clinical and molecular spectrum associated with variants in CENPF

Strømme syndrome (MIM 243605) or a form of syndromic microcephaly have both been reported to be caused by biallelic variants in CENPF. The common features associated with CENPF variants are microcephaly, jejunal atresia and eye abnormalities, but additional case reports have indicated more variable presentations. Here, we describe the diagnosis of an adult with Strømme syndrome and present a review of all 32 cases reported with genetic variants in CENPF, to highlight the common and diverse features. We find that neurological abnormalities, particularly microcephaly, are the most common feature (91% of individuals), with gastrointestinal (69%) and ocular features (44%) less common. While facial dysmorphism is widely reported, there are a broad variety of features noted, with no clear commonalities. The vast majority of genetic variants identified alter the reading frame through either nonsense, frameshift, or more rarely, essential splice site variants. Missense variants are seldomly reported; all are homozygous in affected individuals, but functional evidence has been presented for only one missense variant. Our summary illustrates the breadth of clinical features associated with Strømme syndrome caused by CENPF variants and the molecular genetics of CENPF reported thus far.