Developmental, Cognitive, Ocular Motor, and Neuroimaging Findings Related to SUFU Haploinsufficiency: Unraveling Subtle and Highly Variable Phenotypes.

BACKGROUND: Biallelic SUFU variants have originally been linked to Joubert syndrome, comprising cerebellar abnormalities, dysmorphism, and polydactyly. In contrast, heterozygous truncating variants have recently been associated with developmental delay and ocular motor apraxia, but only a limited number of patients have been reported. Here, we aim to delineate further the mild end of the phenotypic spectrum related to SUFU haploinsufficiency. METHODS: Nine individuals (from three unrelated families) harboring truncating SUFU variants were investigated, including two previously reported individuals (from one family). We provide results from a comprehensive assessment comprising neuroimaging, neuropsychology, video-oculography, and genetic testing. RESULTS: We identified three inherited or de novo truncating variants in SUFU (NM_016169.4): c.895C>T p.(Arg299∗), c.71dup p.(Ala25Glyfs∗23), and c.71del p.(Pro24Argfs∗72). The phenotypic expression showed high variability both between and within families. Clinical features include motor developmental delay (seven of nine), axial hypotonia (five of nine), ocular motor apraxia (three of nine), and cerebellar signs (three of nine). Four of the six reported children had macrocephaly. Neuropsychological and developmental assessments revealed mildly delayed language development in the youngest children, whereas general cognition was normal in all variant carriers. Subtle but characteristic SUFU-related neuroimaging abnormalities (including superior cerebellar dysplasia, abnormalities of the superior cerebellar peduncles, rostrally displaced fastigium, and vermis hypoplasia) were observed in seven of nine individuals. CONCLUSIONS: Our data shed further light on the mild but recognizable features of SUFU haploinsufficiency and underline its marked phenotypic variability, even within families. Notably, neurodevelopmental and behavioral abnormalities are mild compared with Joubert syndrome and seem to be well compensated over time.

The Epidemiological Transition of Surgically Treated Proximal Hip Fractures in Austria over the Course of the Pandemic-Back to Normal or a New Normal?

BACKGROUND: The COVID-19 pandemic has had a significant impact on the treatment protocols of orthopedic and trauma departments, but its specific effect on the mortality of hip fracture patients due to possible delays in surgery remains uncertain. This study aimed to investigate whether the COVID-19 pandemic worsened the mortality of patients with hip fractures. MATERIALS AND METHODS: This study included 246 prospectively enrolled patients who suffered from hip fractures during the Austrian State of Emergency period between 1 March and 30 June 2020 and 2021 and were admitted to a tertiary care trauma center. This cohort was compared with a retrospective control group of 494 patients admitted for hip fractures during the same timeframe in 2017, 2018, and 2019. These groups were compared to a prospective recruited "post-COVID-19 collective consisting of the years 2022 and 2023 including 313 patients. RESULTS: This study found a 22% reduction in admissions during the COVID-19 period compared to the pre-COVID period (p = 0.018), as well as significant changes in gender (p = 0.013) and place of accident (p = 0.049). No other changes in demographic variables were observed. The 30-day mortality rate was 14.67% in the pre-COVID period, compared to 15.18% during the COVID-19 period (p = 0.381). No differences were observed in surgical complication rates or in the relationship between comorbidity burden and survival. CONCLUSION: This study did not show a higher perioperative mortality rate due to COVID-19. However, under current circumstances, with potentially reduced surgical and hospital bed capacities, it is expected that this condition might require a high degree of resources in times when resources are potentially scarce, such as during an ongoing pandemic. LEVEL OF EVIDENCE: Level III.