Facioscapulohumeral muscular dystrophy has been genetically linked to reduced numbers (≤8) of D4Z4 repeats at 4q35 combined with 4A(159/161/168) DUX4 polyadenylation signal haplotype. However, we have recently reported that 1.3% of healthy individuals carry this molecular signature and 19% of subjects affected by facioscapulohumeral muscular dystrophy do not carry alleles with eight or fewer D4Z4 repeats. Therefore, prognosis for subjects carrying or at risk of carrying D4Z4 reduced alleles has become more complicated. To test for additional prognostic factors, we measured the degree of motor impairment in a large group of patients affected by facioscapulohumeral muscular dystrophy and their relatives who are carrying D4Z4 reduced alleles. The clinical expression of motor impairment was assessed in 530 subjects, 163 probands and 367 relatives, from 176 unrelated families according to a standardized clinical score. The associations between clinical severity and size of D4Z4 allele, degree of kinship, gender, age and 4q haplotype were evaluated. Overall, 32.2% of relatives did not display any muscle functional impairment. This phenotype was influenced by the degree of relation with proband, because 47.1% of second- through fifth-degree relatives were unaffected, whereas only 27.5% of first-degree family members did not show motor impairment. The estimated risk of developing motor impairment by age 50 for relatives carrying a D4Z4 reduced allele with 1–3 repeats or 4–8 repeats was 88.7% and 55%, respectively. Male relatives had a mean score significantly higher than females (5.4 versus 4.0, P = 0.003). No 4q haplotype was exclusively associated with the presence of disease. In 13% of families in which D4Z4 alleles with 4–8 repeats segregate, the diagnosis of facioscapulohumeral muscular dystrophy was reported only in one generation. In conclusion, this large-scale analysis provides further information that should be taken into account when counselling families in which a reduced allele with 4–8 D4Z4 repeats segregates. In addition, the reduced expression of disease observed in distant relatives suggests that a family’s genetic background plays a role in the occurrence of facioscapulohumeral muscular dystrophy. These results indicate that the identification of new susceptibility factors for this disease will require an accurate classification of families.

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Based on the 7-year experience of the Italian Clinical Network for FSHD, we revised the FSHD clinical form to describe, in a harmonized manner, the phenotypic spectrum observed in FSHD. The new Comprehensive Clinical Evaluation Form (CCEF) defines various clinical categories by the combination of different features. The inter-rater reproducibility of the CCEF was assessed between two examiners using kappa statistics by evaluating 56 subjects carrying the molecular marker used for FSHD diagnosis. The CCEF classifies: (1) subjects presenting facial and scapular girdle muscle weakness typical of FSHD (category A, subcategories A1–A3), (2) subjects with muscle weakness limited to scapular girdle or facial muscles (category B subcategories B1, B2), (3) asymptomatic/healthy subjects (category C, subcategories C1, C2), (4) subjects with myopathic phenotype presenting clinical features not consistent with FSHD canonical phenotype (D, subcategories D1, D2). The inter-rater reliability study showed an excellent concordance of the final four CCEF categories with a κ equal to 0.90; 95 % CI (0.71; 0.97). Absolute agreement was observed for categories C and D, an excellent agreement for categories A [κ = 0.88; 95 % CI (0.75; 1.00)], and a good agreement for categories B [κ = 0.79; 95 % CI (0.57; 1.00)]. The CCEF supports the harmonized phenotypic classification of patients and families. The categories outlined by the CCEF may assist diagnosis, genetic counseling and natural history studies. Furthermore, the CCEF categories could support selection of patients in randomized clinical trials. This precise categorization might also promote the search of genetic factor(s) contributing to the phenotypic spectrum of disease.Electronic supplementary materialThe online version of this article (doi:10.1007/s00415-016-8123-2) contains supplementary material, which is available to authorized users.

There is growing evidence that lifestyle choices account for the overall quality of health and life (QoL) reflecting many potential lifestyle risks widely associated with alterations of the reproductive function up to the infertility. This review aims to summarize in a critical fashion the current knowledge about the potential effects of stress and QoL on female reproductive function. A specific literature search up to August 2017 was performed in IBSS, SocINDEX, Institute for Scientific Information, PubMed, Web of Science and Google Scholar. Current review highlights a close relationship in women between stress, QoL and reproductive function, that this association is more likely reported in infertile rather than fertile women, and that a vicious circle makes them to have supported each other. However, a precise cause-effect relationship is still difficult to demonstrate due to conflicting results and the lack of objective measures/instruments of evaluation.

Uterine transplantation (UTx) associated with IVF restores fertility in women affected by absolute uterine factor infertility (AUFI). Pregnancies achieved both in women undergoing any solid organ transplantation and following IVF are associated with an increased risk of maternal and neonatal complications. This systematic review evaluated this risk in UTx-IVF treated women focusing on the safety and efficacy features of the treatment. Twenty-two studies and three press releases reporting on 52 UTx-IVF treatments were identified. Regarding the safety of treatment, 38/52 (73,1%) of surgical procedures led to the restoration of uterine function in recipients, 12/52 (23,1%) of recipients experienced post-operative complications requiring hysterectomy, and 2/52 (3,8%) of procedures failed before uterine recipients' surgery due to intra-operative complications. Regarding the efficacy of treatment, results focused on transplanted patients showing full recovery of organ functioning: 16/38 (42,1%) of patients achieved a pregnancy, including two women who gave births twice. UTx-IVF pregnancies led to 16 deliveries and all new-borns were healthy. Six out of 16 (37,5%) UTx pregnancies faced major complications during gestation. Preterm births occurred in 10/16 (62,5%) UTx deliveries. Our data indicates that the risk of gestational and delivery complications deserves important consideration in AUFI women receiving UTx-IVF treatments. However, these observations are preliminary and need to be revised after larger series of data are published.