Neurocognitive and psychosocial function in children with benign external hydrocephalus (BEH)-a long-term follow-up study.

INTRODUCTION: Long-term impact of benign external hydrocephalus (BEH) on cognition is largely unknown, and indication for neurosurgical CSF diversion procedure is debated. This study reports neuropsychological and psychosocial function in operated and non-operated BEH children. METHODS: Eighty-six children (76 males) between 8 and 18 years (mean 13.9) diagnosed with BEH before 12 months were included, of whom 30.2 % were operated. Participants completed neuropsychological tests and questionnaires covering quality of life (PedsQL) and executive function (BRIEF). RESULTS: Both operated and non-operated BEH children performed significantly below normative means on several neuropsychological tests. The children scored themselves higher than the norm average on PedsQL; however, the parents reported life quality comparable to other children. Operated children performed poorer compared with non-operated children on tests of psychomotor speed, attention span, executive function, motor speed and coordination, and on the BRIEF subscale Monitoring. Operated children, but not their parents, reported more problems on PedsQL subscale School than non-operated children. DISCUSSION: Children with BEH display long-term subtle neurocognitive difficulties. Non-operated children performed significantly better on some neuropsychological measures and reported less psychosocial problems. This difference may be caused by a selection bias: neurosurgical intervention was more likely in children with clinically more pronounced symptoms.

Benefits of clinical criteria and high-throughput sequencing for diagnosing children with syndromic craniosynostosis.

An accurate diagnosis of syndromic craniosynostosis (CS) is important for personalized treatment, surveillance, and genetic counselling. We describe detailed clinical criteria for syndromic CS and the distribution of genetic diagnoses within the cohort. The prospective registry of the Norwegian National Unit for Craniofacial Surgery was used to retrieve individuals with syndromic CS born between 1 January 2002 and 30 June 2019. All individuals were assessed by a clinical geneticist and classified using defined clinical criteria. A stepwise approach consisting of single-gene analysis, comparative genomic hybridization (aCGH), and exome-based high-throughput sequencing, first filtering for 72 genes associated with syndromic CS, followed by an extended trio-based panel of 1570 genes were offered to all syndromic CS cases. A total of 381 individuals were registered with CS, of whom 104 (27%) were clinically classified as syndromic CS. Using the single-gene analysis, aCGH, and custom-designed panel, a genetic diagnosis was confirmed in 73% of the individuals (n = 94). The diagnostic yield increased to 84% after adding the results from the extended trio-based panel. Common causes of syndromic CS were found in 53 individuals (56%), whereas 26 (28%) had other genetic syndromes, including 17 individuals with syndromes not commonly associated with CS. Only 15 individuals (16%) had negative genetic analyses. Using the defined combination of clinical criteria, we detected among the highest numbers of syndromic CS cases reported, confirmed by a high genetic diagnostic yield of 84%. The observed genetic heterogeneity encourages a broad genetic approach in diagnosing syndromic CS.