Prenatal findings of cataract and arthrogryposis: recurrence of cerebro-oculo-facio-skeletal syndrome and review of differential diagnosis

Fabio Sirchia,Agnese Feresin,Denise Mordeglia,Valentina Guida,Elisa Giorgio,Ilaria Fantasia,Tamara Stampalija,Moira Barbieri,Alessandro De Luca,Flavio Faletra

doi:10.1186/s12920-021-00939-6

Abstract

BackgroundCerebro-oculo-facio-skeletal syndrome (COFS) is a severe and progressive neurologic condition characterized by prenatal onset of arthrogryposis, cataract, microcephaly and growth failure. The aim of this study was to present a case of recurrence of the COFS syndrome and to propose a differential diagnosis flow-chart in case of prenatal findings of arthrogryposis and cataract.Case presentationWe report a case of recurrence of COFS3 syndrome within the same family, with similar diagnostic features. In the first case the COFS syndrome remained undiagnosed, while in the second case, due to prenatal findings of arthrogryposis and cataract, genetic investigation focusing on responsible genes of COFS (ERCC5, ERCC6 and FKTN genes) was carried out. The fetus was found to be compound heterozygous for two different ERCC5 mutations, confirming the clinical suspect of COFS syndrome. A review of the literature on possible causative genes of prenatal cataract and arthrogryposis was performed and we present a flow-chart to guide differential diagnosis and possible genetic testing in case of these findings.ConclusionCOFS syndrome is a rare autosomic recessive condition. However, it can be suspected and diagnosed prenatally. The flow-chart illustrates a pathway to guide differential diagnosis according to the prenatal findings. Main syndromes, key testing and specific genes are included. Targeted molecular testing should be offered to the couple in order to reach a diagnosis and assess the recurrence risk for future pregnancies.

Highlights

Cerebro-oculo-facio-skeletal syndrome (COFS) is a severe and progressive neurologic condition characterized by prenatal onset of arthrogryposis, cataract, microcephaly and growth failure
The flow-chart illustrates a pathway to guide differential diagnosis according to the prenatal findings
The ERCC5 gene codifies for a structure-specific endonuclease required for making the 3-prime incision during DNA nucleotide excision repair and, contributes to eliminate a broad spectrum of structural DNA lesions [5]. Biallelic mutations in this gene have been associated with different phenotypes from xeroderma pigmentosum (XPG), where manifestations are largely restricted to the skin, to trichothiodystrophy, Cockayne syndrome and the more severe, early-onset COFS3 [6]

Summary

Conclusion

COFS syndrome is a rare autosomic recessive condition. It can be suspected and diagnosed prenatally. The flow-chart illustrates a pathway to guide differential diagnosis according to the prenatal findings. Key testing and specific genes are included. Targeted molecular testing should be offered to the couple in order to reach a diagnosis and assess the recurrence risk for future pregnancies

Background

Findings

Discussion and conclusions