Warsaw syndrome: a cohesinopathy as etiology of primary microcephaly

Abstract

Warsaw Breakage Syndrome (WABS) is a very rare autosomal recessive disease. To date, only 24 cases have been described in medical literature. There are descriptions of patients from various ethnic origins, but only one of them is from Latin America, in Uruguay.

Objective: To report a clinical case from Chile, which presented the classic triad, in order to characterize its phenotype and contribute to the description in Latin America of this syndrome.

Clinical Case: Male patient, second child of consanguineous parents. Pregnancy with intrauterine growth restriction, born preterm at 33 weeks of gestational age, head circumference 24 centimeters (-5 to -6 SD); infectious and metabolic evaluation were normal. Brain MRI without relevant pathological findings. He has left deafness and severe hearing loss in his right ear, using a cochlear implant in the left ear. Head circumference remains always close to -6SD, length and weight below -2SD. Considering the triad of deafness, microcephaly, and growt restriction, whole exome sequencing was performed, finding a homozygous variant likely pathogenic in the DDX11 gene.

Conclusions: The knowledge about this syndrome allows clinical suspicion and, thus, to perform an early genetic study that allows confirming or ruling out the diagnosis, providing adequate genetic counseling, and having a correct prognosis estimation. Medical literature on this is limited and does not allow us to make exact estimates on the evolution of each patient, however, the report of new cases such as ours, contributes to the knowledge and management of other patients with the syndrome.