CRTAP-Related Osteogenesis Imperfecta: Clinical Variability and a Potential Founder Variant in CRTAP

CRTAP-related osteogenesis imperfecta (OI) is a form of OI that ranges from moderate (type IV) to extremely severe (type II) and is caused by biallelic variants in the CRTAP gene. To date, only about 30 cases have been reported in the literature.

We describe two adults and one fetus with molecularly confirmed CRTAP-related OI.

The phenotype varied extensively in terms of severity and clinical features, ranging from moderate (type IV) to severe (type III) and including cases with prenatal fractures as well as one case with a low number of fractures and no prenatal fractures. Interestingly, 1 patient presented with high myopia and bilateral retinal detachment, which have not been previously reported in OI type VII. Regarding molecular results, we identified three CRTAP variants that have not been previously reported in the literature. One of the variants was found in both a woman and an unrelated fetus of Cape Verdean descent, suggesting that the carrier frequency of this variant in the Cape Verde population may be relatively high.

We expand the clinical spectrum of patients with CRTAP variants and highlight the clinical variability of this extremely rare type of OI, which may present with either prenatal or postnatal onset. Our findings also underscore the importance of investigating the role of CRTAP in extra-skeletal tissues and assessing potential founder effects in underrepresented populations.