Autism spectrum disorders in boys at a major UK hemophilia center: prevalence and risk factors

Background: Autism spectrum disorders (ASDs) are diagnosed by social communication difficulties strong, narrow interests, and repetitive stereotyped behavior. An apparently-elevated prevalence of ASD at a major UK hemophilia center warranted investigation. Objectives: To screen boys with hemophilia for difficulties in social communication and executive function and identify the prevalence and risk factors for ASD. Methods: Parents of boys with hemophilia aged 5 to 16 years completed the Social Communication Questionnaire, Children’s Communication Checklist, and the Behavior Rating Inventory of executive function. Prevalence and potential risk factors for ASD were evaluated. Boys with an existing diagnosis of ASD did not complete questionnaires, but were included in the prevalence analysis. Results: Negative scores on all 3 questionnaires were observed for 60 of 79 boys. Positive scores on 1, 2, and 3 questionnaires were seen in 12 of 79, 3 of 79, and 4 of 79 boys, respectively. In addition to the 11 of 214 boys with a prior ASD diagnosis, 3 further boys were diagnosed with ASD, yielding a prevalence of 14 (6.5%) of 214, greater than that of boys in the UK general population. Premature birth was linked to having ASD, but did not fully explain the increased prevalence with more boys born <37 weeks scoring positively on the Social Communications Questionnaire and Children’s Communication Checklist compared with those born at term. Conclusion: This study identified an increased prevalence of ASD at 1 UK hemophilia center. Prematurity was identified as a risk factor but did not fully explain the higher prevalence of ASD. Further investigation in the wider national/global hemophilia communities is warranted to determine whether this is an isolated finding

Deep phenotyping of 89 xeroderma pigmentosum patients reveals unexpected heterogeneity dependent on the precise molecular defect

Xeroderma pigmentosum (XP) is a rare DNA repair disorder characterized by increased susceptibility to UV radiation (UVR)-induced skin pigmentation, skin cancers, ocular surface disease, and, in some patients, sunburn and neurological degeneration. Genetically, it is assigned to eight complementation groups (XP-A to -G and variant). For the last 5 y, the UK national multidisciplinary XP service has provided follow-up for 89 XP patients, representing most of the XP patients in the United Kingdom. Causative mutations, DNA repair levels, and more than 60 clinical variables relating to dermatology, ophthalmology, and neurology have been measured, using scoring systems to categorize disease severity. This deep phenotyping has revealed unanticipated heterogeneity of clinical features, between and within complementation groups. Skin cancer is most common in XP-C, XP-E, and XP-V patients, previously considered to be the milder groups based on cellular analyses. These patients have normal sunburn reactions and are therefore diagnosed later and are less likely to adhere to UVR protection. XP-C patients are specifically hypersensitive to ocular damage, and XP-F and XP-G patients appear to be much less susceptible to skin cancer than other XP groups. Within XP groups, different mutations confer susceptibility or resistance to neurological damage. Our findings on this large cohort of XP patients under long-term follow-up reveal that XP is more heterogeneous than has previously been appreciated. Our data now enable provision of personalized prognostic information and management advice for each XP patient, as well as providing new insights into the functions of the XP proteins