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Background Mutations of TCF4, which encodes a basic helix-loop-helix transcription factor, cause Pitt-Hopkins syndrome (PTHS) via multiple genetic mechanisms. TCF4 is a complex locus expressing multiple transcripts by alternative splicing and use of multiple promoters. To address the relationship between mutation of these transcripts and phenotype, we report a three-generation family segregating mild intellectual disability with a chromosomal translocation disrupting TCF4. Results Using whole genome sequencing, we detected a complex unbalanced karyotype disrupting TCF4 (46,XY,del(14)(q23.3q23.3)del(18)(q21.2q21.2)del(18)(q21.2q21.2)inv(18)(q21.2q21.2)t(14;18)(q23.3;q21.2)(14pter®14q23.3::18q21.2®18q21.2::18q21.1®18qter;18pter®18q21.2::14q23.3®14qter). Subsequent transcriptome sequencing, qRT-PCR and nCounter analyses revealed that cultured skin fibroblasts and peripheral blood had normal expression of genes along chromosomes 14 or 18 and no marked changes in expression of genes other than TCF4. Affected individuals had 12–33 fold higher mRNA levels of TCF4 than did unaffected controls or individuals with PTHS. Although the derivative chromosome generated a PLEKHG3-TCF4 fusion transcript, the increased levels of TCF4 mRNA arose from transcript variants originating distal to the translocation breakpoint, not from the fusion transcript. Conclusions Although validation in additional patients is required, our findings suggest that the dysmorphic features and severe intellectual disability characteristic of PTHS are partially rescued by overexpression of those short TCF4 transcripts encoding a nuclear localization signal, a transcription activation domain, and the basic helix-loop-helix domain. Electronic supplementary material The online version of this article (doi:10.1186/s13023-016-0439-6) contains supplementary material, which is available to authorized users.

Body image disturbance has been listed as a diagnostic feature of several psychopathological conditions (1-5). As body image concerns appear in children as young as 5 years old, it was hypothesized to be an important risk factor for the development of psychopathology, such as Eating Disorders (ED) in adolescence. Results of the current review of the literature support this hypothesis and suggest that young children can (1) estimate as accurately as adults their body size, and (2) show similar cognitive distortions, cognitive biases, and the negative emotions associated with their body image. There is some evidence that children can (1) display severe symptoms of body image distortion such as is present in body dysmorphic disorder (BDD), (2) demonstrate negative stereotypes toward obesity and (3) internalize thin ideal body im- age. Research suggests that some of the key factors involved in children's body satisfaction is parental perception and di- rect comments from peers. Body dissatisfaction can predict body image related psychopathology later in development. In conclusion, intervention and prevention of eating disorders with children under the age of 7 is arguably a viable strategy, and cognitive and behavioural training could involve parents, teachers, mental health practitioners as well as the child him/herself. This training and education should cover early manifestation of body image disturbance and their associated risk factors.