We present histological and molecular analyses of the developing human cerebellum from 30 days after conception to 9 months after birth. Differences in developmental patterns between humans and mice include spatiotemporal expansion of both ventricular and rhombic lip primary progenitor zones to include subventricular zones containing basal progenitors. The human rhombic lip persists longer through cerebellar development than in the mouse and undergoes morphological changes to form a progenitor pool in the posterior lobule, which is not seen in other organisms, not even in the nonhuman primate the macaque. Disruptions in human rhombic lip development are associated with posterior cerebellar vermis hypoplasia and Dandy-Walker malformation. The presence of these species-specific neural progenitor populations refines our insight into human cerebellar developmental disorders.

Medulloblastoma (MB) comprises a group of heterogeneous paediatric embryonal neoplasms of the hindbrain with strong links to early development of the hindbrain [1][2][3][4] . Mutations that activate Sonic hedgehog signalling lead to Sonic hedgehog MB in the upper rhombic lip (RL) granule cell lineage [5][6][7][8] . By contrast, mutations that activate WNT signalling lead to WNT MB in the lower RL 9,10 . However, little is known about the more commonly occurring group 4 (G4) MB, which is thought to arise in the unipolar brush cell lineage 3,4 . Here we demonstrate that somatic mutations that cause G4 MB converge on the core binding factor alpha (CBFA) complex and mutually exclusive alterations that affect CBFA2T2, CBFA2T3, PRDM6, UTX and OTX2. CBFA2T2 is expressed early in the progenitor cells of the cerebellar RL subventricular zone in Homo sapiens, and G4 MB transcriptionally resembles these progenitors but are stalled in developmental

Foetal MRI is an additional imaging modality in the diagnosis of cerebral ischemic-haemorrhagic lesions, and it is useful in providing further information on the extension of the parenchymal injury and associated abnormalities, thus improving delivery management.

Sirenomelia and VACTERL association are defects of blastogenesis of unknown cause. Although they appear clinically distinct, some epidemiological and experimental studies suggest a common pathogenetic mechanism. We report on the reproductive history of a 28-year-old obese, diabetic mother who had three pregnancies. The first resulted in the birth of a sirenomelic child, the second in a miscarriage, while the third was terminated for fetal malformations, diagnosed post-mortem as VACTERL association. This observation supports the relationship between sirenomelia and VACTERL, which probably represent the two ends of the same phenotypic spectrum. Their occurrence in the same sibship also indicates a possible common cause. The coexistence with maternal diabetes seems more than a chance occurrence and the constellation of malformations observed in the present family may be explained as the pleiotropic effect of the same teratogenic agent interacting with genetic predisposition to diabetes and/or obesity.

BackgroundThrombocytopenia–absent radius syndrome is a rare autosomal recessive disorder characterized by megakaryocytic thrombocytopenia and longitudinal limb deficiencies mostly affecting the radial ray. Most patients are compound heterozygotes for a 200 kb interstitial microdeletion in 1q21.1 and a hypomorphic allele in RBM8A, mapping in the deleted segment. At the moment, the complete molecular characterization of thrombocytopenia–absent radius syndrome is limited to a handful of patients mostly ascertained in the pediatric ageCase presentationWe report on a fetus with bilateral upper limb deficiency found at standard prenatal ultrasound examination. The fetus had bilateral radial agenesis and humeral hypo/aplasia with intact thumbs, micrognathia and urinary anomalies, indicating thrombocytopenia–absent radius syndrome. Molecular studies demonstrated compound heterozygosity for the 1q21.1 microdeletion and the RBM8A rs139428292 variant at the hemizygous state, inherited from the mother and father, respectivelyConclusionThe molecular information allowed prenatal diagnosis in the following pregnancy resulting in the birth of a healthy carrier female. A review was carried out with the attempt to the trace the fetal ultrasound presentation of thrombocytopenia–absent radius syndrome and discussing opportunities for second-tier molecular studies within a multidisciplinary setting.