Fabio Sirchia1, Ilaria Fantasia2, Agnese Feresin3, Elisa Giorgio4, Flavio Faletra5, Denise Mordeglia3, Moira Barbieri2, Valentina Guida6, Alessandro De Luca6, Tamara Stampalija2,3. 1. Department of Molecular Medicine, University of Pavia, Via Forlanini 14, 27100, Pavia, Italy. sirchiafabio@gmail.com. 2. Unit of Fetal Medicine e Prenatal Diagnosis, Institute for Maternal and Child Health IRCCS "Burlo Garofolo", Trieste, Italy. 3. Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy. 4. Department of Medical Sciences, University of Torino, Turin, Italy. 5. Department of Medical Genetics, Institute for Maternal and Child Health IRCCS "Burlo Garofolo", Trieste, Italy. 6. Division of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, 71013, San Giovanni Rotondo, Foggia, Italy.
Abstract
BACKGROUND: 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 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 PRESENTATION: We 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. CONCLUSION: COFS 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.
BACKGROUND: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 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 PRESENTATION: We 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. CONCLUSION:COFS 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.
Entities:
Keywords:
Arthrogryposis; COFS3; Case report; ERCC5 gene; Fetal growth restriction
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