Development, behaviour and sensory processing in Marshall-Smith syndrome and Malan syndrome: phenotype comparison in two related syndromes.

BACKGROUND: Ultrarare Marshall-Smith and Malan syndromes, caused by changes of the gene nuclear factor I X (NFIX), are characterised by intellectual disability (ID) and behavioural problems, although questions remain. Here, development and behaviour are studied and compared in a cross-sectional study, and results are presented with genetic findings. METHODS: Behavioural phenotypes are compared of eight individuals with Marshall-Smith syndrome (three male individuals) and seven with Malan syndrome (four male individuals). Long-term follow-up assessment of cognition and adaptive behaviour was possible in three individuals with Marshall-Smith syndrome. RESULTS: Marshall-Smith syndrome individuals have more severe ID, less adaptive behaviour, more impaired speech and less reciprocal interaction compared with individuals with Malan syndrome. Sensory processing difficulties occur in both syndromes. Follow-up measurement of cognition and adaptive behaviour in Marshall-Smith syndrome shows different individual learning curves over time. CONCLUSIONS: Results show significant between and within syndrome variability. Different NFIX variants underlie distinct clinical phenotypes leading to separate entities. Cognitive, adaptive and sensory impairments are common in both syndromes and increase the risk of challenging behaviour. This study highlights the value of considering behaviour within developmental and environmental context. To improve quality of life, adaptations to environment and treatment are suggested to create a better person-environment fit.

Clinical and molecular characterization of two patients with palmoplantar keratoderma-congenital alopecia syndrome type 2.

Palmoplantar keratoderma-congenital alopecia (PPKCA) syndrome is a rare genodermatosis, with two clinically recognizable forms: dominant (Type 1) and recessive (Type 2). Reports of only 18 patients have been published to date, and the molecular basis of the condition is unknown. We describe two cases with PPKCA Type 2 (PPKCA2), comprising a novel patient, originally reported as an example of autosomal ichthyosis follicularis-atrichia-photophobia syndrome, and the 6-year follow-up of a previously published case. Extensive molecular studies of both patients excluded mutations in all the known genes associated with PPK and partially overlapping syndromes. The striking similarities between these two patients confirm PPKCA2 as a discrete genodermatosis, of which the main features are congenital and universal alopecia, diffuse keratosis pilaris, facial erythema, and a specific PPK with predominant involvement of the fingertips and borders of the hands and feet, with evolution of sclerodactyly, contractures and constrictions. Clinical follow-up of these patients has demonstrated progressive worsening of the hand involvement and attenuation of facial erythema.

[Public health strategies in the prevention of induced abortion. An experience of interprofessional education based strategy]. / Strategie di Sanità pubblica nella Prevenzione delle IVG. Una esperienza basata sulla formazione interprofessionale.

In Italy recent statistics show a huge difference between abortion rate among Italian and migrant women: is it an inequity in health? The Italian Ministry of Health / Center for Disease Prevention and Control, which recognized this issue as a specific public health problem, has financed a national Project whose aim was the prevention of abortion among migrant women. The Project was characterized by a multitasking approach: 1) information and health education of migrant women and their communities; 2) education of health and social care professionals; 3) analysis and development of new proposals for the networks of services directed towards the improvement of woman's health. In this article the Authors describe the main characteristics of the realized intervention of inter-professional education. It began with a multidisciplinary process for the identification of educational needs which has allowed the identification of educational goals. A Training of Trainers event was then organized in order to involve and make the ten Italian Regions partners of the Project aware of their responsibilities. A DVD collecting all the material of the course and other useful resources was produced in order to support the educational process. At the moment it is not possible to evaluate the medium- and long-time results of the process (e.g. the efficacy of educational interventions or the health outcomes related to the reduction of abortion among migrant women). Nevertheless all the actors involved have made positive evaluations on the usefulness of the process.

De novo deletion of 1q31.1-q32.1 in a patient with developmental delay and behavioral disorders.

We describe the case of a 6-year-old boy with a de novo deletion of the long arm of chromosome 1 encompassing band 1q31.1-q32.1, minor facial anomalies, mild developmental delay, and behavioral disorders. His postnatal karyotype was normal. Using array-comparative genomic hybridization, we identified and characterized a de novo 1q interstitial deletion of about 15.6 Mb, which partially overlaps those of other reported cases. We considered the gene content of the deleted region in an attempt to compare the clinical features of our patient with these other cases, even though they were not characterized molecularly in detail. The most remarkable difference was the absence of microcephaly. To the best of our knowledge, this is the first report of a de novo 1q31.1-q32.1 deletion. Moreover, it illustrates how molecular delineation associated with fine clinical characterization can improve the genotype-phenotype correlations of classical cytogenetic abnormalities.

Identification of de novo mutations and rare variants in hypoplastic left heart syndrome.

Hypoplastic left heart syndrome (HLHS) is one of the most severe congenital heart malformations, characterized by underdevelopment of the structures in the left heart-aorta complex. The majority of cases are sporadic. Although multiple genetic loci have been tentatively implicated in HLHS, no gene or pathway seems to be specifically associated with the disease. To elucidate the genetic basis of HLHS, we analyzed 53 well-characterized patients with isolated HLHS using an integrated genomic approach that combined DNA sequencing of five candidate genes (NKX2-5, NOTCH1, HAND1, FOXC2 and FOXL1) and genome-wide screening by high-resolution array comparative genomic hybridization. In 30 patients, we identified two novel de novo mutations in NOTCH1, 23 rare patients inherited gene variants in NOTCH1, FOXC2 and FOXL1, and 33 rare patients mostly inherited copy-number variants. Some of the identified variations coexisted in the same patient. The biological significance of such rare variations is unknown, but our findings strengthen the role of NOTCH pathway in cardiac valve development, indicating that HLHS is, at least in part, a 'valve' disease. This is the first report of de novo mutations associated with isolated HLHS. Moreover, the coexistence of multiple rare variants suggests in some cases a cumulative effect, as shown for other complex disease.

Familial occurrence of isolated right ventricular hypoplasia.

Isolated right ventricular hypoplasia is a rare congenital anomaly. This condition is usually associated with a communication between the atria in the form of a patent foramen ovale or secondum atrial septal defect. We describe a familial occurrence of this rare disease. A 1-day-old male child and his 34-year-old father were found to have isolated right ventricular hypoplasia with atrial septal defect. An autosomal dominant mode of inheritance is likely for this rare congenital anomaly.

Evaluation of the endocrine function of the heart in humans: proposal for an integrated approach for the assessment of production, secretion, distribution and degradation of atrial natriuretic factor and related peptides.

It has become established that heart has an endocrine function because it synthesizes and secretes a family of peptide hormones, called Atrial Natriuretic Peptide (ANP), with potent diuretic, natriuretic, vascular smooth muscle-relaxing activity and complex interactions with the hormonal and nervous systems. Because ANP has important volume-regulatory characteristics, it is postulated to play a central role in volume homoeostasis under normal conditions and in several pathophysiological states, such as congestive heart failure. ANP is able to counterbalance all the detrimental effects of activation of the neuro-hormonal system in patients with heart failure may lead to new therapeutical protocols that can prevent the progression from compensation to overt heart failure. An integrated approach for the assessment of the endocrine function of the heart is proposed, consisting of four different, but complementary, steps: 1) evaluation of gene expression of ANP in the myocardial cell; 2) determination of circulating and tissue levels of ANP; 3) in-vivo assessment of the main turnover parameters of the hormone; 4) studies on localization and identification of ANP receptors. These procedures have been employed in physiological, pharmacological and/or clinical studies. The development and the standardization of new methods for the assessment of endocrine function of the heart will not only increase our understanding of the physiological regulation of production, secretion, and function, and of the pathophysiological role of ANP and its related peptides, but also may pave the way for further progress concerning our knowledge of more general physiological and pathophysiological mechanisms of the cardiovascular system itself.