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Wolf-Hirschhorn syndrome is a well-defined disorder due to 4p16.3 deletion, characterized by distinct facial features, intellectual disability, prenatal and postnatal growth retardation, and seizures. Genotype-phenotype correlations based on differently sized deletions have been attempted, and some candidate genes have been suggested. We report on clinical characteristics of three patients with pure interstitial submicroscopic 4p16.3 deletions, ranging in size from 68 to 166 kb, involving WHSCR1 and/or part of WHSCR2, and review published cases with overlapping 4p16.3 losses. The present study highlights a major role of NSD2 gene in the pathogenesis of the WHS main features and predicts that loss-of-function mutations affecting NSD2 gene could result in microcephaly, prenatal and postnatal growth retardation, psychomotor and language delay, and craniofacial features. Absent seizures in all subjects corroborate the suggestion that this specific feature is causally linked with at least one additional causative gene. Finally, we suggest that mir-943 could play a role in the pathogenesis of CHD in some of these patients.

Smith-Magenis syndrome (SMS) is a complex genetic disorder caused by interstitial 17p11.2 deletions encompassing multiple genes, including the retinoic acid induced 1 gene-RAI1-or mutations in RAI1 itself. The clinical spectrum includes developmental delay, cognitive impairment, and behavioral abnormalities, with distinctive physical features that become more evident with age. No patients have been reported to have had offspring. We here describe a girl with developmental delay, mainly compromising the speech area, and her mother with mild intellectual disabilities and minor dysmorphic features. Both had sleep disturbance and attention deficit disorder, but no other atypical behaviors have been reported. In both, CGH-array analysis detected a 15q13.3 interstitial duplication, encompassing CHRNA7. However, the same duplication has been observed in several, apparently healthy, maternal relatives. We, thus, performed a whole exome sequencing analysis, which detected a frameshift mutation in RAI1, de novo in the mother, and transmitted to her daughter. No other family members carried this mutation. This is the first report of an SMS patient having offspring. Our experience confirms the importance of searching for alternative causative genetic mechanisms in case of confounding/inconclusive findings such as a CGH-array result of uncertain significance. © 2016 Wiley Periodicals, Inc.

During the 18th century in Naples, Raimondo di Sangro, Prince of Sansevero, completed works on the family chapel, the so-called "Cappella Sansevero." The chapel houses statues of extraordinary beauty and spectacularly detailed but also, in the basement, two human skeletons known as the "Anatomical Machines" ("Macchine Anatomiche"). These two skeletons, a man and a pregnant woman, are entirely surrounded by their circulatory systems, just as if these were suddenly fixed. Legend, believed as truth until few years ago, says that Prince Raimondo had prepared and injected an unknown embalming substance in the blood vessels of two of his servants convicting them to eternal fixity. Recent investigations have demonstrated that, while the bones are authentic, the blood vessels are actually extraordinary artifacts that also reproduce some congenital malformations. The dreadful aspect of these two skeletons appears to be in strident contrast with the classic beauty of the statues which glorify and celebrate the ideal of morphology. Conversely, the two Anatomical Machines, protagonists of legends and superstitions since centuries, represent a marvelous example of science mixed with art.