Di Feo Maria Francesca, Bettio Cinzia, Salsi Valentina, Bertucci Emma, Tupler Rossella
Department of Biomedical, Metabolic and Neural Sciences University of Modena and Reggio Emilia Modena Italy.
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health (DINOGMI) University of Genoa Genova Italy.
Health Sci Rep. 2022 Apr 20;5(3):e614. doi: 10.1002/hsr2.614. eCollection 2022 May.
This is the first national population-based report about prenatal diagnosis for families with a history of facioscapulohumeral muscular dystrophy (FSHD), a complex hereditary disease. The incomplete disease penetrance and the phenotypic heterogeneity observed in carriers of D4Z4 alleles of reduced size, the FSHD molecular hallmark, make the estimate of genetic risk problematic.
We considered all requests of preconception counseling and prenatal diagnosis received between January 2008 and December 2020 by the genetic counseling service associated with the Italian National Registry for FSHD (INRF). A multidisciplinary team managed the clinical and molecular data of each family.
Between 2008 and 2020, 60 couples required preconception counseling (PC) for FSHD. In 52 couples was observed at least one partner carried a D4Z4 reduced allele (DRA). Out of these 52 couples, 47 had a follow-up visit routine yearly. Out of these 47, 26 (55.3%) couples had children: eight asked for prenatal diagnosis (PND), two had assisted reproduction by heterologous in vitro fertilization (IVF), and 16 did not require further assistance. Regarding PND, 50 prenatal analyses were performed for 36 couples. The test resulted positive in 27 pregnancies, 12 (44.4%) were terminated, and 15 (55.6%) were carried to term.
The different choices made by the couples show the importance of an integrated approach to support genetic counseling for FSHD. These results remark the relevance of the clinical and molecular investigation of the extended family, preferably before conception.
这是首份基于全国人口的关于面肩肱型肌营养不良症（FSHD，一种复杂的遗传性疾病）家族产前诊断的报告。FSHD的分子标志是大小减小的D4Z4等位基因携带者中观察到的疾病不完全外显率和表型异质性，这使得遗传风险评估存在问题。
我们考虑了2008年1月至2020年12月期间意大利全国FSHD登记处（INRF）相关遗传咨询服务收到的所有孕前咨询和产前诊断请求。一个多学科团队管理每个家庭的临床和分子数据。
2008年至2020年期间，60对夫妇因FSHD需要孕前咨询（PC）。在52对夫妇中，观察到至少一方携带D4Z4减小等位基因（DRA）。在这52对夫妇中，47对每年进行常规随访。在这47对夫妇中，26对（55.3%）有孩子：8对要求进行产前诊断（PND），2对通过异源体外受精（IVF）进行辅助生殖，16对不需要进一步帮助。关于PND，为36对夫妇进行了50次产前分析。检测结果在27次妊娠中呈阳性，12次（44.4%）妊娠终止，15次（55.6%）妊娠足月分娩。
夫妇们做出的不同选择表明了综合方法对支持FSHD遗传咨询的重要性。这些结果表明了对大家庭进行临床和分子调查的相关性，最好在受孕前进行。
