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

Biallelic CENPF variants, mostly frameshifting (nonsense, frameshift, essential splice-site).

Report of the diagnosis of an adult with Strømme syndrome and a review of the 32 reported cases with CENPF variants (MIM 243605). Neurological abnormalities, especially microcephaly, are the most frequent feature (91 % of individuals), ahead of gastrointestinal (69 %) and ocular features (44 %). The vast majority of variants alter the reading frame (nonsense, frameshift or, more rarely, essential splice sites); missense variants are rare, always homozygous, with functional evidence for only one. The review illustrates the breadth of the clinical spectrum associated with CENPF.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

A useful synthesis for genetic counselling: it clarifies the relative penetrance of features (near-constant microcephaly, more variable gastrointestinal and ocular involvement) and confirms loss of function as the dominant mechanism. The diagnosis in an adult broadens the age of recognition of a syndrome often perceived as severe and early-onset. Interpreting the rare CENPF missense variants remains a point of caution given the lack of functional data.

Analysis by Dr Thibaut Benquey