PURPOSE:MYRF-related cardiac-urogenital syndrome (MYRF-CUGS) is a rare condition associated with heterozygous MYRF variants. The description of MYRF-CUGS phenotype is mostly based on postnatal cases and 36 affected individuals have been published so far. We aim now to delineate the prenatal phenotype of MYRF-CUGS by reporting clinical data from fetuses and neonates with a pathogenic MYRF variant. METHODS:Detailed radiographic, pathological, clinical, and molecular data from 12 prenatal cases were collected through an international collaborative study. Adding the five fetuses previously published, we were able to study a cohort of 17 cases. RESULTS:Main ultrasound-accessible manifestations of MYRF-CUGS include congenital heart defects (13/17, 76%), congenital diaphragmatic hernia (10/17, 59%) and disorders of sexual differentiation in 46, XY fetuses (7/14; 50%). Postnatal examination and/or autopsy data highlighted additional birth defects and neurological findings with a large spectrum of severity. Molecular results revealed ten previously unpublished variants, one missense and nine predicted truncating variants (three frameshift, three nonsense and three splice site variants). CONCLUSION:We report the first prenatal cohort of MYRF-CUGS, allowing us to further characterize the variable expressivity of this rare disorder in fetuses. Severe congenital anomalies with a poor prognosis are more frequent than previously described in postnatal cases. Our data suggest that MYRF-CUGS is characterized by a recurrent recognizable malformative association, accessible to prenatal diagnosis, with a significant intrafamilial phenotypic variability making genetic counseling challenging.

The translocation of SRY onto one of the two X chromosomes results in a 46,XX testicular disorder of sex development; this is supposedly because of non‐allelic homologous recombination between the protein kinase X gene (PRKX) and the inverted protein kinase Y pseudogene (PRKY). Although 46,XX SRY‐positive men are infertile, the literature data indicate that some of these individuals are of short stature (relative to the general population). We sought to determine whether short stature was linked to additional, more complex chromosomal rearrangements.

Potocki-Schaffer syndrome includes multiple exostoses, parietal foramina, and variable developmental delay/intellectual disability. It is associated with a heterozygous deletion of the 11p12p11.2 region. In some cases, the deletion extends to the WAGR locus (11p13p12). We describe here a 9-month-old girl harboring the largest germline heterozygous deletion characterized so far. Oligohydramnios and parietal foramina were noticed during pregnancy. No patient has been diagnosed before with concomitance of these two syndromes during the prenatal period. Cytogenetic diagnosis was anticipated on basis of clinical and radiological signs. Postnatal conventional karyotype confirmed an interstitial 11p deletion: 46,XX,del(11)(p11.2p15.1). Array-comparative genomic hybridization characterized a 29.6 Mb deletion. Our case illustrates the interest of high-resolution genomic approaches to correlate adequately clinical phenotypes with specific genes in suspected contiguous gene deletion syndromes.

Multiple isodicentric Y chromosomes [idic(Y)] is a rare cytogenetic abnormality, most exclusively described in constitutional karyotypes. Only recently has this entity been reported in hematologic neoplasms such as myeloid disorders, albeit these cases remain very scarce. The possible involvement of increasing copies of potential proto-oncogenes located on the multiple idic(Y) led to consider one of them, CRLF2, as a target for kinase inhibitors. We report here, to our knowledge, the first case of multiple idic(Y) in a patient with myelofibrosis secondary to essential thrombocythemia. The patient received ruxolitinib therapy with initial good clinical response.

BNAR syndrome (MIM608980) is a very rare condition: nine cases belonging to three unrelated families were reported since its first description in 2002. The distinctive clinical feature is the bifidity of the tip of the nose and its association with anorectal and/or renal anomalies. Its molecular basis consisting of biallelicFREM1missense or nonsense mutations was elucidated after studying the original Egyptian family and was confirmed in two families originating from Afghanistan and Pakistan. We describe a fourth family originating from Turkey with signs challenging the diagnostic criteria suggested by the description of the three reported families.