It is well established that somatic genomic changes can influence phenotypes in cancer, but the role of adaptive changes in developmental disorders is less well understood. Here we have used next-generation sequencing approaches to identify de novo heterozygous mutations in sterile α motif domain–containing protein 9 (SAMD9, located on chromosome 7q21.2) in 8 children with a multisystem disorder termed MIRAGE syndrome that is characterized by intrauterine growth restriction (IUGR) with gonadal, adrenal, and bone marrow failure, predisposition to infections, and high mortality. These mutations result in gain of function of the growth repressor product SAMD9. Progressive loss of mutated SAMD9 through the development of monosomy 7 (–7), deletions of 7q (7q–), and secondary somatic loss-of-function (nonsense and frameshift) mutations in SAMD9 rescued the growth-restricting effects of mutant SAMD9 proteins in bone marrow and was associated with increased length of survival. However, 2 patients with –7 and 7q– developed myelodysplastic syndrome, most likely due to haploinsufficiency of related 7q21.2 genes. Taken together, these findings provide strong evidence that progressive somatic changes can occur in specific tissues and can subsequently modify disease phenotype and influence survival. Such tissue-specific adaptability may be a more common mechanism modifying the expression of human genetic conditions than is currently recognized.

Women in many countries are advised to use folic acid supplements before and early during pregnancy to reduce the risk of neural tube defects in their infants. This study aimed to update the prevalence and to identify possible determinants of preconception folic acid supplement use in Italian women. The study was based on cross-sectional data from seven maternity clinics located in six Italian regions from January to June, 2012. Data on maternal characteristics and supplement use were collected for 2,189 women using a self-administered questionnaire. Preconception folic acid use was reported by 23.5 % (n = 515) of the participants. Of these, 479 (93 %) women had taken folic acid supplements on a daily basis as recommended by the health authorities. Women who both had intended their pregnancy and had requested a preconception health visit to a doctor/gynecologist were substantially more likely than the reference group to initiate folic acid supplementation before their pregnancy (48.6 versus 4.8 %). Preconception folic acid use was also associated with higher maternal age, higher education, marriage/cohabitation, lower parity, infertility treatments, and chronic disease. Data from seven maternity clinics located in six Italian regions indicate that preconception folic acid supplement use in many Italian women is low. Women who do not plan their pregnancy or do not request a preconception health visit to their doctor have among the lowest prevalence of preconception folic acid use. Improving folate status in these and other supplemental non-users may have important disease preventive effects.

Hypospadias is a congenital displacement of the urethral meatus in male newborns, being either an isolated defect at birth or a sign of sexual development disorders. The aim of this study was to assess the prevalence rate of hypospadias in different Districts of Italy, in order to make a comparison with other countries all over the world. We reviewed all the newborns file records (years 2001–2004) in 15 Italian Hospitals. We found an overall hypospadias prevalence rate of 3.066 ± 0.99 per 1000 live births (82.48% mild hypospadias, 17.52% moderate-severe). In newborns Small for Gestational Age (birthweight < 10^th percentile) of any gestational age the prevalence rate of hypospadias was 6.25 per 1000 live births. Performing multivariate logistic regression analysis for different degrees of hypospadias according to severity, being born SGA remained the only risk factor for moderate-severe hypospadias (p = 0.00898) but not for mild forms (p > 0.1). In our sample the prevalence of hypospadias results as high as reported in previous European and American studies (3–4 per 1000 live births). Pathogenesis of isolated hypospadias is multifactorial (genetic, endocrine and environmental factors): however, the prevalence rate of hypospadias is higher in infants born small for gestational age than in newborns with normal birth weight.

The early identification of pre-lingual deafness is necessary to minimize the consequences of hearing impairment on the future communication skills of a baby. According to the most recent international guidelines the deafness diagnosis must occur before the age of three months and the prosthetic-rehabilitative treatment with a traditional hearing aid should start within the first six months. When a Cochlear implant becomes necessary, the treatment should start between the age of 12 months and 18 months. The only way to diagnose the problem early is the implementation of universal neonatal audiological screening programs. Transient evoked otoacoustic emissions (TEOAE) is the most adequate test because it's accurate, economic and of simple execution. Automatic auditory brainstem response (AABR) is necessary to identify patients with auditory neuropathy but it is also important to reduce the number of false-positives.The 20-30% of infant hearing impairment is represented by progressive or late-onset hearing loss (HL) so it's also necessary to establish an audiological follow up program, especially in infants at risk.