ObjectiveTo clinically, genetically, and radiologically characterize a large cohort of SPG7 patients.MethodsWe used data from next-generation sequencing panels for ataxias and hereditary spastic paraplegia to identify a characteristic phenotype that helped direct genetic testing for variations in SPG7. We analyzed MRI. We reviewed all published SPG7 mutations for correlations.ResultsWe identified 42 cases with biallelic SPG7 mutations, including 7 novel mutations, including a large multi-exon deletion, representing one of the largest cohorts so far described. We identified a characteristic phenotype comprising cerebellar ataxia with prominent cerebellar dysarthria, mild lower limb spasticity, and a waddling gait, predominantly from a cohort of idiopathic ataxia. We report a rare brain MRI finding of dentate nucleus hyperintensity on T2 sequences with SPG7 mutations. We confirm that the c.1529C>T allele is frequently present in patients with long-standing British ancestry. Based on the findings of the present study and existing literature, we confirm that patients with homozygous mutations involving the M41 peptidase domain of SPG7 have a younger age at onset compared to individuals with mutations elsewhere in the gene (14 years difference, p < 0.034), whereas c.1529C>T compound heterozygous mutations are associated with a younger age at onset compared to homozygous cases (5.4 years difference, p < 0.022).ConclusionsMutant SPG7 is common in sporadic ataxia. In patients with British ancestry, c.1529C>T allele represents the most frequent mutation. SPG7 mutations can be clinically predicted by the characteristic hybrid spastic-ataxic phenotype described above, along with T2 hyperintensity of the dentate nucleus on MRI.
Objective To establish the endometrial cancer detection rate in women using hormone replacement therapy presenting with postmenopausal bleeding. Study Design Retrospective cohort study. Setting and population Rapid access gynaecology clinic at a tertiary hospital. Women aged under 60 years referred with postmenopausal bleeding. Methods Retrospective study of referrals received between 1 January 2019 and 31 December 2020 including Hormone replacement therapy (HRT) use and histological diagnosis. Main outcome measures Histological diagnosis of endometrial cancer, borderline ovarian tumour or endometrial intraepithelial neoplasia. Statistical analysis Chi squared test Results 1363 women were included. 214 women were using HRT when they experienced PMB and only one of these had endometrial cancer at histology (cancer detection rate 0.47%). 25 of the 1124 women who were not using HRT were diagnosed with endometrial cancer on histology (cancer detection rate 2.18%). Chi squared statistical analysis confirmed this was statistically significant ( p value .0156). Conclusions The endometrial cancer detection rate in women aged under 60 years using HRT with PMB is very low. Referral on a two-week wait pathway for suspected cancer diagnosis induces stress and anxiety for the woman and may lead to more invasive initial investigation even though other diagnoses are far more likely. Women aged under 60 years with postmenopausal bleeding that have either commenced HRT or had a change to their preparation within the last 6 months should be seen on a less urgent referral pathway if necessary given the very low probability of endometrial cancer.
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