P-352 Investigating the association between DMPK CTG repeats and female hypogonadism in patients affected by Type 1 Myotonic Dystrophy

Abstract

Abstract Study question Is DPKM CTG repeat size correlated with hypogonadism in female patients affected by type 1 Myotonic Dystrophy? Summary answer The size of CTG repeats in DPKM gene seems to be correlated with hypogonadism severity in female patients affected by type 1 Myotonic Dystrophy. What is known already Type 1 Myotonic Dystrophy (DMT1) is an autosomal dominant degenerative genetic disorder caused by CTG repeats in a single copy of DMPK gene. It is characterized by a broad phenotypic spectrum and a progressive course, involving primarily the muscular and endocrine systems. While DMT1 is a very well-known cause of male hypogonadism, the relationship between DMPK CTG repeats and female hypogonadism is almost unexplored yet. Study design, size, duration We performed a cross–sectional risk study in a cohort of 60 women, with a mean age of 31.5 years (18 to 45 years), referred to our Medical Genetics service for either suspected DMT1 or hypogonadism. The study duration was one year (from November 2022 to November 2023). Participants/materials, setting, methods We performed a DMPK–CTG analysis to investigate a possible correlation between CTG and hypogonadism. Based on the analysis, 11 women were diagnosed with DMT1 with associated hypogonadism, 11 with DMT1 without hypogonadism, 22 did not show DMPK expansion but were affected by hypogonadism, while the remaining 16 showed neither DMPK expansion nor hypogonadism. The patients affected by DMT1 performed standard karyotyping, FRAXA and FRAXE genetic testing to exclude alternative genetic causes of premature ovarian failure. Main results and the role of chance Our results, are indicative that the severity of hypogonadism in DMT1 patients may correlate with the size of CTG repeats. DMPK CTG repeats ranging from 150 – 1000 (range E2) were associated with milder forms of hypogonadism, while the patients having DMPK expansions within the E3 range (1000 CTG repeats or more) showed hypergonadotropic hypogonadism with both infertility and failure of medically assisted reproduction. Limitations, reasons for caution The female patients showing neither DMPK expansion nor hypogonadism did not perform other genetic analysis except DMPK-CTG testing. Moreover, due to the low sample size, our results did not reach statistical significance for a definitive conclusion. Wider implications of the findings To the best of our knowledge, this is the first study to show a possible correlation between female hypogonadism and DMPK CTG repeat size in female patients with type 1 myotonic dystrophy. These results, although preliminary, represent a first step in understanding a hitherto misrecognized clinical consequence of the disease. Trial registration number Not applicable