title: Novel features of 3q29 deletion syndrome: Results from the 3q29 registry.
abstract: 3q29 deletion syndrome is caused by a recurrent, typically de novo heterozygous 1.6 Mb deletion, but because incidence of the deletion is rare (1 in 30,000 births) the phenotype is not well described. To characterize the range of phenotypic manifestations associated with 3q29 deletion syndrome, we have developed an online registry (3q29deletion.org) for ascertainment of study subjects and phenotypic data collection via Internet-based survey instruments. We report here on data collected during the first 18 months of registry operation, from 44 patients. This is the largest cohort of 3q29 deletion carriers ever assembled and surveyed in a systematic way. Our data reveal that 28% of registry participants report neuropsychiatric phenotypes, including anxiety disorder, panic attacks, depression, bipolar disorder, and schizophrenia. Other novel findings include a high prevalence (64%) of feeding problems in infancy and reduced weight at birth for 3q29 deletion carriers (average reduction 13.9 oz (394 g), adjusted for gestational age and sex, P = 6.5e-07). We further report on the frequency of heart defects, autism, recurrent ear infections, gastrointestinal phenotypes, and dental phenotypes, among others. We also report on the expected timing of delayed developmental milestones. This is the most comprehensive description of the 3q29 deletion phenotype to date. These results are clinically actionable toward improving patient care for 3q29 deletion carriers, and can guide the expectations of physicians and parents. These data also demonstrate the value of patient-reported outcomes to reveal the full phenotypic spectrum of rare genomic disorders.
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Megan R
authors.initials: MR
authors.lastname: Glassford
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Rosenfeld
authors.affiliation: Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia.
authors.forename: Alexa A
authors.initials: AA
authors.lastname: Freedman
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia.|Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Zwick
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia.|Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia.
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: Mulle
mesh_terms: D001321:Autistic Disorder / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000175:diagnosis / Q000235:genetics; D002893:Chromosomes, Human, Pair 3; D002658:Developmental Disabilities / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007859:Learning Disabilities / Q000235:genetics; D008297:Male; D010641:Phenotype; D012042:Registries; D013577:Syndrome
keywords: 3q29 deletion; 3q29 microdeletion; autism spectrum disorder; copy number variation; developmental delay; genomic disorders; patient-reported outcomes; schizophrenia