Delineating the genotypic and phenotypic spectrum of HECW2-related neurodevelopmental disorders

Background Variants in HECW2 have recently been reported to cause a neurodevelopmental disorder with hypotonia, seizures and impaired language; however, only six variants have been reported and the clinical characteristics have only broadly been defined. Methods Molecular and clinical data were collected from clinical and research cohorts. Massive parallel sequencing was performed and identified individuals with a HECW2-related neurodevelopmental disorder. Results We identified 13 novel missense variants in HECW2 in 22 unpublished cases, of which 18 were confirmed to have a de novo variant. In addition, we reviewed the genotypes and phenotypes of previously reported and new cases with HECW2 variants (n=35 cases). All variants identified are missense, and the majority of likely pathogenic and pathogenic variants are located in or near the C-terminal HECT domain (88.2%). We identified several clustered variants and four recurrent variants (p.(Arg1191Gln);p.(Asn1199Lys);p.(Phe1327Ser);p.(Arg1330Trp)). Two variants, (p.(Arg1191Gln);p.(Arg1330Trp)), accounted for 22.9% and 20% of cases, respectively. Clinical characterisation suggests complete penetrance for hypotonia with or without spasticity (100%), developmental delay/intellectual disability (100%) and developmental language disorder (100%). Other common features are behavioural problems (88.9%), vision problems (83.9%), motor coordination/movement (75%) and gastrointestinal issues (70%). Seizures were present in 61.3% of individuals. Genotype-phenotype analysis shows that HECT domain variants are more frequently associated with cortical visual impairment and gastrointestinal issues. Seizures were only observed in individuals with variants in or near the HECT domain. Conclusion We provide a comprehensive review and expansion of the genotypic and phenotypic spectrum of HECW2 disorders, aiding future molecular and clinical diagnosis and management.Peer reviewe

Juvenile Homicide Offenders Look Back 35 Years Later: Reasons They Were Involved in Murder

Murders committed by juveniles have been a serious concern in the United States for more than 50 years. Decisions by the United States Supreme Court during the 21st century have reduced the likelihood that juvenile homicide offenders will be sentenced to life without parole (LWOP). As a result of these decisions, hundreds of prisoners who were sentenced as juveniles for murder to LWOP under mandatory sentencing statutes or its equivalent are now eligible for the reconsideration of their sentences. In light of these changes in sentencing policies and practices, follow-up research on juveniles convicted of murder is essential. This research is part of a 35-year follow-up study of 59 boys who were convicted of murder and sentenced to adult prisons in a southeastern state, and initially interviewed in the early 1980s. Twenty of these men agreed to participate in clinical interviews during which they reflected upon the reasons (i.e., motives, circumstances) for which they got involved in criminal behavior as juveniles. These reasons, which broadly tap tenets of psychological and sociological theories, were analyzed in terms of predominance. Thereafter, the attention focuses on looking at the relationship of these 20 reasons to recidivism among the 18 juvenile homicide offenders (JHOs) who have been released from prison. JHOs who lived in neighborhoods where crime was routine and who engaged in crime because the opportunity presented itself were approximately 20 and 22.50 times more likely to be arrested post release and returned to prison, respectfully. The implications of these findings, the limitations of the study, and suggestions for future research are discussed

Kathleen Heide

Kathleen Heide discusses her career at USF during which she has acted as a Professor of Criminology and Associate Dean for Faculty and Program Development in the College of Arts & Sciences

Kathleen Heide

Kathleen Heide discusses her career at USF during which she has acted as a Professor of Criminology and Associate Dean for Faculty and Program Development in the College of Arts & Sciences

Juvenile Homicide Offenders: Factors in Desistance after Incarceration

While several prior studies have examined the prevalence and predictors of recidivism among juvenile homicide offenders (JHOs), much less scholarly attention has been devoted to exploring the post-release factors that influence JHOs to desist from criminal behavior. Given relatively recent rulings by the U.S. Supreme Court, individuals who commit homicide offenses as juveniles are less likely to spend the rest of their lives in prison. Accordingly, it is important to understand the factors associated with desistance in the post-incarceration lives of JHOs. The present study was designed to assess the effects of post-release factors on JHOs’ recidivism outcomes, using a sample of 19 male JHOs from a southeastern U.S. state who were convicted as adults and sentenced to serve time in prison in the 1980s. These men were interviewed approximately 35 years after their original homicide offense about their adjustment to life in prison and after release, as well as their reasons for engaging in criminal behavior during adolescence. Thematic qualitative analysis was used to identify the post-release factors that were prevalent in the lives of the JHOs who desisted from crime. These five factors included avoiding old neighborhood and friends, positive intimate relationship, stable employment, human agency, and generativity. The implications of the findings for the prevention of recidivism among JHOs, as well as avenues for future research, are discussed