Phenotypic expansion of the BPTF-related neurodevelopmental disorder with dysmorphic facies and distal limb anomalies

Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (NEDDFL), defined primarily by developmental delay/intellectual disability, speech delay, postnatal microcephaly, and dysmorphic features, is a syndrome resulting from heterozygous variants in the dosage-sensitive bromodomain PHD finger chromatin remodeler transcription factor BPTF gene. To date, only 11 individuals with NEDDFL due to de novo BPTF variants have been described. To expand the NEDDFL phenotypic spectrum, we describe the clinical features in 25 novel individuals with 20 distinct, clinically relevant variants in BPTF, including four individuals with inherited changes in BPTF. In addition to the previously described features, individuals in this cohort exhibited mild brain abnormalities, seizures, scoliosis, and a variety of ophthalmologic complications. These results further support the broad and multi-faceted complications due to haploinsufficiency of BPTF.Genetics of disease, diagnosis and treatmen

Enhancing the quality of extended life years. Identification of the oldest old with a very good and very poor quality of life

The objective of the study was to investigate quality of life in very old age by analyzing what proportion of older people had cumulative difficulties across several domains of quality of life, what proportion had no or few problems, and how these distributions changed over time. The design was a structured interview survey of people living in Hackney aged 85 and over at baseline, at two points in time. The follow-up interviews took place 2.5-3 years after the baseline interviews. The sample formed a census of all people aged 85 and over living in an East London borough, identified from centralized family doctors' records, validated against the electoral register. Respondents were interviewed at home by one of 12 trained interviewers. The subjects were 630 people aged 85 and over living at home, at baseline (70% response rate); 78% of survivors were re-interviewed. The main outcome measures were nine variables which were used to represent three major domains of quality of life: perceived 'wellbeing and autonomy','health and activity' (these two areas can be categorized under 'health and well being') and 'environment'. These were selected on the basis of the literature and information from focus groups held with study members, and measured using validated measurement scales and items. They were analyzed by respondents' sociodemographic characteristics, and features of their lives, and mortality up to 30 months after baseline. Close to half of older people achieved 'good' scores/on at least five of the nine indicators of quality of life used. Few people achieved 'good' scores on all nine items, or 'poor' scores on most items. The deterioration or increase in scores between the baseline and follow-up interviews among surviving sample members was not substantial. There was an association between number of 'good' quality of life scores and mortality within 30 months of baseline interview. The study confirms the great diversity of the elderly population, even in relatively homogeneous areas, and the need to adopt a multidimensional perspective on quality of life in old age. The study is unique in its longitudinal analysis of a very elderly population, and in adopting a multifaceted approach, rather than analyzing each domain of quality of life separately