Primrose syndrome is a rare autosomal dominant condition caused by heterozygous missense variants within ZBTB20. Through an exome sequencing approach (as part of the Deciphering Developmental Disorders [DDD] study) we have identified five unrelated individuals with previously unreported, de novo ZBTB20 pathogenic missense variants. All five missense variants targeted the C2H2 zinc finger domains. This genotype-up approach has allowed further refinement of the Primrose syndrome phenotype. Major characteristics (>90% individuals) include an intellectual disability (most frequently in the moderate range), a recognizable facial appearance and brain MRI abnormalities, particularly abnormalities of the corpus callosum. Other frequent clinical associations (in 50-90% individuals) include sensorineural hearing loss (83%), hypotonia (78%), cryptorchidism in males (75%), macrocephaly (72%), behavioral issues (56%), and dysplastic/hypoplastic nails (57%). Based upon these clinical data we discuss our current management of patients with Primrose syndrome. K E Y W O R D SDDD study, exome sequencing, intellectual disability, Primrose syndrome, ZBTB20

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Background Outcomes following the antenatal detection of a cystic hygroma are reported as poor. Most studies examining the outcome from antenatal diagnosis of a fetal anomaly are published from tertiary referral centres and these may not, therefore, reflect the true overall outcomes from these pregnancies. An early investigation from EMSYCAR 1997–1999 suggested a ‘normal’ outcome for <10% of such pregnancies.1 Method All cases of cystic hygroma prenatally diagnosed and reported to EMSYCAR, from 2000 to 2009, were identified. Pregnancy outcomes and confirmation of anomaly details following delivery were collected as part of the routine data follow-up for registry cases. Results Over the 10 year period there were 653 687 births and 498 antenatally diagnosed cases of cystic hygroma: a population prevalence of 1:1313 births (95% CI 1:1202 to 1:1436). Of these 285 (57.2%) were TOPs, of which nearly two thirds (n=179, 62.8%) had an abnormal karyotype, 48 (16.8%) had further anomalies and 58 (20.4%) were isolated cases of cystic hygroma. Median gestation at TOP was 13 weeks (range 11 to 29) with 258/285 (90%) occurring <20 weeks – before any spontaneous regression of the hygroma, noted in other studies, might have occurred. 213 (42.8%) of the antenatally diagnosed cases opted to continue the pregnancy of which 90 (42%) resulted in a livebirth where the cystic hygroma had resolved and there were no reported anomalies. Conclusion Parental counselling may need to be revised in view of these improved outcomes and the possibility of spontaneous regression of early diagnosed cases of cystic hygroma.