Proximal 6q (6q11-q15) deletions are extremely rare and little is known about their phenotypic consequences. Since parents and caregivers now use social media to seek information on rare disorders, the Chromosome 6 Project has successfully collaborated with a Facebook group to collect data on individuals worldwide. Here we describe a cohort of 20 newly identified individuals and 25 literature cases with a proximal 6q deletion. Microarray results and phenotype data were reported directly by parents via a multilingual online questionnaire. This led to phenotype descriptions for five subregions of proximal 6q deletions; comparing the subgroups revealed that 6q11q14.1 deletions presented less severe clinical characteristics than 6q14.2q15 deletions. Gastroesophageal reflux, tracheo/laryngo/bronchomalacia, congenital heart defects, cerebral defects, seizures, and vision and respiratory problems were predominant in those with 6q14.2q15 deletions. Problems related to connective tissue (hypermobility, hernias and foot deformities) were predominantly seen in deletions including the COL12A1 gene (6q13). Congenital heart defects could be linked to deletions of MAP3K7 (6q15) or TBX18 (6q14.3). We further discuss the role of ten genes known or assumed to be related to developmental delay and/or autism (BAI3, RIMS1, KCNQ5, HTR1B, PHIP, SYNCRIP, HTR1E, ZNF292, AKIRIN2 and EPHA7). The most influential gene on the neurodevelopmental phenotype seems to be SYNCRIP (6q14.3), while deletions that include more than two of these genes led to more severe developmental delay. We demonstrate that approaching individuals via social media and collecting data directly from parents is a successful strategy, resulting in better information to counsel families.

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Background: Even with the introduction of new genetic techniques that enable accurate genomic characterization, knowledge about the phenotypic spectrum of rare chromosomal disorders is still limited, both in literature and existing databases. Yet this clinical information is of utmost importance for health professionals and the parents of children with rare diseases. Since existing databases are often hampered by the limited time and willingness of health professionals to input new data, we collected phenotype data directly from parents of children with a chromosome 6 disorder. These parents were reached via social media, and the information was collected via the online Chromosome 6 Questionnaire, which includes 115 main questions on congenital abnormalities, medical problems, behaviour, growth and development. Here, we assess data consistency by comparing parent-reported phenotypes to phenotypes based on copies of medical files for the same individual and data availability by comparing the data available on specific characteristics reported by parents to data available in existing literature. Results: The reported answers to the main questions on phenotype characteristics were 85-95% consistent, and the consistency of answers to subsequent more detailed questions was 77-96%. For all but two main questions, significantly more data was collected from parents via the Chromosome 6 Questionnaire than was currently available in literature. For the topics developmental delay and brain abnormalities, no significant difference in the amount of available data was found. The only feature for which significantly more data was available in literature was a sub-question on the type of brain abnormality present. Conclusions: This is the first study to compare phenotype data collected directly from parents to data extracted from medical files on the same individuals. We found that the data was highly consistent, and phenotype data collected via the online Chromosome 6 Questionnaire resulted in more available information on most clinical characteristics when compared to phenotypes reported in literature reports thus far. We encourage active patient participation in rare disease research and have shown that parent-reported phenotypes are very reliable and contribute to our knowledge of the phenotypic spectrum of rare chromosomal disorders.