More than meets the eye: expanding and reviewing the clinical and mutational spectrum of brittle cornea syndrome

Tibbe Dhooge, Tim Van Damme, Delfien Syx, Laura Muiño Mosquera, Sheela Nampoothiri, Anil Radhakrishnan, Pelin Ozlem Simsek-Kiper, Gülen Eda Utine, Maryse Bonduelle, Isabelle Migeotte, Osama Essawi, Serdar Ceylaner, Adila Al Kindy, Brad Tinkle, Sofie Symoens, Fransiska Malfait

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2 Citaten (Scopus)

Samenvatting

Brittle cornea syndrome (BCS) is a rare autosomal recessive disorder characterized by corneal thinning and fragility, leading to corneal rupture, the main hallmark of this disorder. Non-ocular symptoms include not only hearing loss but also signs of connective tissue fragility, placing it in the Ehlers-Danlos syndrome (EDS) spectrum. It is caused by biallelic pathogenic variants in ZNF469 or PRDM5, which presumably encode transcription factors for extracellular matrix components. We report the clinical and molecular features of nine novel BCS families, four of which harbor variants in ZNF469 and five in PRDM5. We also performed a genotype- and phenotype-oriented literature overview of all (n = 85) reported patients with ZNF469 (n = 53) and PRDM5 (n = 32) variants. Musculoskeletal findings may be the main reason for referral and often raise suspicion of another heritable connective tissue disorder, such as kyphoscoliotic EDS, osteogenesis imperfecta, or Marfan syndrome, especially when a corneal rupture has not yet occurred. Our findings highlight the multisystemic nature of BCS and validate its inclusion in the EDS classification. Importantly, gene panels for heritable connective tissue disorders should include ZNF469 and PRDM5 to allow for timely diagnosis and appropriate preventive measures for this rare condition.

Originele taal-2English
Pagina's (van-tot)711-730
Aantal pagina's20
TijdschriftHuman Mutation
Volume42
Nummer van het tijdschrift6
Vroegere onlinedatum2021
DOI's
StatusPublished - 6 apr 2021

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