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.

Keywords: 3q29 deletion; 3q29 microdeletion; autism spectrum disorder; copy number variation; developmental delay; genomic disorders; patient-reported outcomes; schizophrenia.

Figure 1

The distribution of birth weight (blue) and gestational age (red) in the 3q29 deletion registry population (top) and US natality data for 2012 (bottom). There are differences in birth weight (3q29 deletion registry participants, mean = 6.09 lbs; 2012 US general population, mean = 7.2 lbs) and gestational age (3q29 deletion registry participants, mean = 37.95 w; 2012 US general population, mean = 38.71 w). After adjusting for sex and gestational age, 3q29 deletion carriers are predicted to weigh 0.86 lbs less at birth than babies in the general population. [Color figure can be seen in the online version of this article, available at http://wileyonlinelibrary.com/journal/ajmga].

Figure 2

Problems in the first year of life reported in 3q29 deletion registry participants. [Color figure can be seen in the online version of this article, available at http://wileyonlinelibrary.com/journal/ajmga].

Figure 3

Time‐to‐event curves for four exemplar developmental milestones. The dashed green line indicates the time at which 50% of typically developing children achieve the milestone [Dosman et al., 2012]; the dashed blue line indicates when 50% of 3q29 deletion registry participants are reported to achieve the same milestone. [Color figure can be seen in the online version of this article, available at http://wileyonlinelibrary.com/journal/ajmga].

Figure 4

The distribution of neuropsychiatric conditions reported by 3q29 deletion registry participants. [Color figure can be seen in the online version of this article, available at http://wileyonlinelibrary.com/journal/ajmga].