ARTÍCULOS Y NOVEDADES

• Microarray and FISH-based genotype-phenotype analysis of 22 Japanese patients with Wolf-Hirschhorn syndrome. Am J Med Genet A. 2014 Mar. Shimizu K. Department of Medical Genetics, Shinshu niversity School of Medicine, Matsumoto, Japan.

          Wolf-Hirschhorn syndrome (WHS) is a contiguous gene deletion syndrome of the distal 4p chromosome, characterized by craniofacial features, growth impairment, intellectual disability, and seizures. Although genotype-phenotype correlation studies have previously been published, several important issues remain to be elucidated including seizure severity. We present detailed clinical and molecular-cytogenetic findings from a microarray and fluorescence in situ hybridization (FISH)-based genotype-phenotype analysis of 22 Japanese WHS patients, the first large non-Western series. 4p deletions were terminal in 20 patients and interstitial in two, with deletion sizes ranging from 2.06 to 29.42 Mb. The new Wolf-Hirschhorn syndrome critical region (WHSCR2) was deleted in all cases, and duplication of other chromosomal regions occurred in four. Complex mosaicism was identified in two cases: two different 4p terminal deletions; a simple 4p terminal deletion and an unbalanced translocation with the same 4p breakpoint. Seizures began in infancy in 33% (2/6) of cases with small (<6 Mb) deletions and in 86% (12/14) of cases with larger deletions (>6 Mb). Status epilepticus occurred in 17% (1/6) with small deletions and in 87% (13/15) with larger deletions. Renal hypoplasia or dysplasia and structural ocular anomalies were more prevalent in those with larger deletions. A new susceptible region for seizure occurrence is suggested between 0.76 and 1.3 Mb from 4pter, encompassing CTBP1 and CPLX1, and distal to the previously-supposed candidate gene LETM1. The usefulness of bromide therapy for seizures and additional clinical features including hypercholesterolemia are also described.

• Two cases of hepatic adenomas in patients with Wolf-Hirschhorn syndrome: a new rare complication? Am J Med Genet A. 2013 Jul. Prunotto G. Pediatric Genetic Unit, Pediatric Department of Monza Brianza per il Bambino e la sua Mamma (MBBM) Foundation, S.Gerardo Hospital, Monza, Italy.

       Wolf-Hirschhorn syndrome (WHS) is a rare microdeletion syndrome associated with a characteristic facial appearance, failure to thrive, psychomotor delays, and various major malformations of internal organs; many medical complications have been described (feeding difficulties, epilepsy, hearing problems). Benign or malignant oncologic problems are not a typical feature of the natural history of these patients. We report on two patients with WHS patients in whom hepatic adenoma (HA) were diagnosed during adolescence. The clinical evolution of liver involvement was different between the two. We discuss the possibility of considering HA as a rare medical problem in the follow-up of WHS patients.

*** Síndrome  de  genes  contiguos: debido  a  que  el  tamaño  de  la  región  perdida  es diferente en muchos casos, se ha considerado que las variaciones clínicas podrían deberse a los  distintos  genes perdidos  en  cada  caso  y,  por  tanto, se  habla  de  un  síndrome  de  genes contiguos.***