A case of G1013R FBN1 mutation: A potential genotype-phenotype correlation in severe Marfan syndrome.

Marfan Syndrome (MFS) is an autosomal dominant connective tissue disorder with a wide range of severities. Ninety-five percent of MFS probands have a mutation in the fibrillin-1 gene (FBN1); however, there are a high number of unique mutations complicating attempts at establishing any phenotype-genotype correlations for this disease (Tiecke et al., European Journal of Human Genetics, 2001, 9, 13-21). One of the few extant genotype-phenotype correlations is in exon 24-32 which have been associated with a severe pediatric presentation of neonatal MFS with predominately cardiovascular symptoms. We present a 24-year-old male patient with a heterozygous de novo variant NM_000138.4: c.3037G>A (p.G1013R) located in exon 25 of the FBN1 gene. The patient was found to have dysplastic mitral and tricuspid valves with dilated aortic root at 9 months of age. This is a notable case in that the location of this patient's mutation and his age of symptom onset would indicate a guarded prognosis. Further, this mutation, FBN1 G1013R, has been reported in the literature in four other unrelated patients all of whom presented at a young age with cardiac involvement and all of whom had relative longevity when compared to other patients with mutations in this exon 24-32 hot spot. These findings may represent a more specific genotype-phenotype correlation within this mutational hot spot.

Rare SUZ12 variants commonly cause an overgrowth phenotype.

The Polycomb repressive complex 2 is an epigenetic writer and recruiter with a role in transcriptional silencing. Constitutional pathogenic variants in its component proteins have been found to cause two established overgrowth syndromes: Weaver syndrome (EZH2-related overgrowth) and Cohen-Gibson syndrome (EED-related overgrowth). Imagawa et al. (2017) initially reported a singleton female with a Weaver-like phenotype with a rare coding SUZ12 variant-the same group subsequently reported two additional affected patients. Here we describe a further 10 patients (from nine families) with rare heterozygous SUZ12 variants who present with a Weaver-like phenotype. We report four frameshift, two missense, one nonsense, and two splice site variants. The affected patients demonstrate variable pre- and postnatal overgrowth, dysmorphic features, musculoskeletal abnormalities and developmental delay/intellectual disability. Some patients have genitourinary and structural brain abnormalities, and there may be an association with respiratory issues. The addition of these 10 patients makes a compelling argument that rare pathogenic SUZ12 variants frequently cause overgrowth, physical abnormalities, and abnormal neurodevelopmental outcomes in the heterozygous state. Pathogenic SUZ12 variants may be de novo or inherited, and are sometimes inherited from a mildly-affected parent. Larger samples sizes will be needed to elucidate whether one or more clinically-recognizable syndromes emerge from different variant subtypes.

Implications for school nursing through interprofessional education and practice.

AIMS AND OBJECTIVES: To explore the interprofessional collaboration between nursing and social work professionals in their delivery of health services for schoolchildren. BACKGROUND: Interprofessional education has long been recommended as a way to meet the need for effective collaboration in school health service with a view to improving the quality of health care. No local study in Hong Kong has looked specifically at how nursing and social work professionals carry out school health services through interprofessional education and practice. Therefore, an examination was conducted of collaboration on a community-based school caring project. DESIGN: A qualitative design was employed, using semi-structured interviews, field observation and field debriefing. METHODS: Seven nursing students and five social work students were recruited and interviewed in 2011. The transcripts were analysed using qualitative content analysis. RESULTS: Three themes were identified: (1) early identification of children's needs through interprofessional collaboration for health promotion, (2) prompt referral for schoolchildren in need, and (3) comprehensive planning and implementation of school health service. CONCLUSION: The strength of collaborative work between nursing and social work professionals is that it helps to identify and address these complex health needs of children. Healthcare providers are hence able to develop a fuller understanding of children's problems, which in turn enables them to provide appropriate and effective health promotion interventions. RELEVANCE TO CLINICAL PRACTICE: The development of interprofessional education for school health services should be envisaged by the local higher educational institute and policy makers to reduce children's risk-taking behaviours and promote their health and well-being. Health educators and health policy makers can better understand how interprofessional education and collaboration can promote children health service for regional and national policy and practice.