Holoprosencephaly

Holoprosencephaly (HPE) is a complex brain malformation resulting from incomplete cleavage of the prosencephalon, occurring between the 18th and the 28th day of gestation and affecting both the forebrain and the face. It is estimated to occur in 1/16,000 live births and 1/250 conceptuses. Three ranges of increasing severity are described: lobar, semi-lobar and alobar HPE. Another milder subtype of HPE called middle interhemispheric variant (MIHF) or syntelencephaly is also reported. In most of the cases, facial anomalies are observed in HPE, like cyclopia, proboscis, median or bilateral cleft lip/palate in severe forms, ocular hypotelorism or solitary median maxillary central incisor in minor forms. These latter midline defects can occur without the cerebral malformations and then are called microforms. Children with HPE have many medical problems: developmental delay and feeding difficulties, epilepsy, instability of temperature, heart rate and respiration. Endocrine disorders like diabetes insipidus, adrenal hypoplasia, hypogonadism, thyroid hypoplasia and growth hormone deficiency are frequent. To date, seven genes have been positively implicated in HPE: Sonic hedgehog (SHH), ZIC2, SIX3, TGIF, PTCH, GLI2 and TDGF1. A molecular diagnosis can be performed by gene sequencing and allele quantification for the four main genes SHH, ZIC2, SIX3 and TGIF. Major rearrangements of the subtelomeres can also be identified by multiplex ligation-dependent probe amplification (MLPA). Nevertheless, in about 70% of cases, the molecular basis of the disease remains unknown, suggesting the existence of several other candidate genes or environmental factors. Consequently, a "multiple-hit hypothesis" of genetic and/or environmental factors (like maternal diabetes) has been proposed to account for the extreme clinical variability. In a practical approach, prenatal diagnosis is based on ultrasound and magnetic resonance imaging (MRI) rather than on molecular diagnosis. Treatment is symptomatic and supportive, and requires a multidisciplinary management. Child outcome depends on the HPE severity and the medical and neurological complications associated. Severely affected children have a very poor prognosis. Mildly affected children may exhibit few symptoms and may live a normal life

Research during medical school: is it particularly difficult in developing countries compared to developed countries?

Manjunath Siddaiah-Subramanya,1,2 Harveen Singh,3 Kor Woi Tiang1,2 1Department of Surgery, Logan Hospital, 2Department of Medicine, Griffith University, 3Department of Gastroenterology, Lady Cilento Children’s Hospital, Brisbane, QLD, Australia Objectives: Medical student involvement in research has been declining over the years. We reviewed the factors that hinder participation in research with a focus on developing countries. Methods: Literature search was performed using PubMed, MEDLINE and Cochrane Library. Peer-reviewed articles published between 1995 and 2017 were screened for relevance to identify key factors affecting medical student involvement in research with a particular focus on developing world. Analytical review is presented here in this article in relation to commonly reported aspects related to research during medical school. Results: This search revealed varied contributing factors that hinder students’ growth and interest in research. It commonly highlighted few aspects in relation to research during medical school, and they were “variability in research uptake among students and issues related to them, their knowledge and attitude toward research and organizational input and its influence on students”. Conclusion: While early introduction to research by inculcating a mindset aimed at research has been proposed, it has not been seen in practice during either the medical school or beyond to an extent that was expected. It appears that developing countries, while they share some of the reasons with developed countries, have their own set of difficulties, which are influenced by culture, beliefs and priorities. Keywords: developing country, developed country, medical student, undergraduate, research&nbsp