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A set of twin brothers with Klinefelter’s syndrome were seen in community paediatric clinic following concern about severe learning disabilities requiring special educational needs school. As Klinefelter’s is not commonly associated with severe learning disabilities, they were enrolled in the 100,000 genome project. Whole exome sequencing revealed a mutation involving the SOX5 gene on chromosome 12p12, which is associated with Lamb-Shaffer syndrome. Lamb-Shaffer syndrome is a neurodevelopmental disorder characterised by global developmental delay, learning disability, poor expressive speech and mild dysmorphic facial features (Nesbitt et al 2015). Less than 100 cases have been reported since the condition was first described in 2012. This new genetic diagnosis has enabled the health care professionals and the parents to understand more about the clinical features, including what surveillance and investigations the patients may require based upon other reported cases with the same mutation. For parents and patients, having a named diagnosis allows them to connect via support groups with other families who have been diagnosed with the same condition. Historically the ‘diagnostic odyssey’ in a child with a rare disease could continue for many years, with serial testing of different genes, often with no answers found for patients or their parents. Learning disability is genetically heterogeneous and has previously presented challenges for molecular diagnoses using traditional genetic testing methods. Next generation sequencing has made it possible to sequence millions of fragments of DNA simultaneously, enabling the sequencing of whole patient exomes as part of the 100,000 genome project. These patients are two of many new genetic diagnoses that are a result of the genome project, which are highlighting the utility of exome sequencing in clinically and genetically heterogeneous conditions such as learning disability. In this unusual case these twins have two different genetic underlying conditions, which demonstrates the importance of investigating further possible causes when previous diagnoses do not explain the evolving clinical phenotype.

The value of and need for paediatric outpatient review attendance as perceived by parents, children, consultants, and general practitioners (GPs) were assessed. One hundred and ninety one parents of 239 children over 7 years of age undergoing review were randomly selected for a semistructured interview. For each parent interviewed, an audit questionnaire was completed after case note review by another paediatrician. A random sample of the patients' GPs was surveyed by postal questionnaire. Twenty per cent of parents and 26% of GPs felt that the GP could care for the child as well as or better than the hospital, whereas only 6% of consultants felt this to be so. Regarding future attendance of the child at the hospital, 48% of parents and 32% of GPs felt the child could either be discharged or seen when parents were worried, whereas consultants felt 24% of patients should have been discharged.