Prenatal Genetic Counseling in Congenital Anomalies

The impact of genetic variability on embryogenesis and fetus development established medical genetics as essential for the prevention of congenital anomalies, early detection and appropriate management. Advances in ultrasonography equipment and technique allow early detection of many congenital malformations. In addition, genetic testing can be performed in a prenatal setting on a variety of biological samples obtained by invasive and noninvasive procedures: chorionic villus sampling, amniocentesis, cordocentesis, or maternal blood collection (i.e., cell free fetal DNA). In the past, only a small percentage of congenital anomalies had a readily identifiable etiology; genetic diagnostic procedures can provide at least some of the answers for the remaining unsolved cases. Undoubtedly, the need for appropriate case management and counseling justifies the importance of uncovering the underlying genetic cause of birth defects. In this chapter, we will focus on genetic counseling in congenital anomalies, including isolated congenital anomalies and preimplantation genetic diagnosis. Genetic counseling provides information and support, assisting parents in making informed decisions. Through this process, parents learn about the risk of having a newborn with a congenital malformation and the nature of the disorder and its natural history, are advised on available testing for that particular case, and discuss options for risk management and family planning

Chronic Calcifying Pancreatitis Associated with Secondary Diabetes Mellitus and Hepatosplenic Abscesses in a Young Male Patient: A Case Report

Background: Chronic pancreatitis (CP) has been described as a multifactorial, ongoing inflammatory condition of the pancreas of varying intensity that produces persistent pain, leading to exocrine and endocrine insufficiency and a decreased lifespan. Currently, there are three primary forms of chronic pancreatitis: chronic autoimmune pancreatitis (steroid-sensitive pancreatitis), chronic obstructive pancreatitis, and chronic calcific pancreatitis, the latter being closely related to excessive alcohol consumption for one or even two decades before the onset of symptoms. Case report: We present the case of a 29 year old man who required medical attention for a significant unintentional weight loss and a history of upper abdominal pain. Blood tests revealed substantial abnormalities, and the patient was admitted for further investigation. CT and MRI confirmed the presence of a pancreatic pseudocyst and extensive pancreatic parenchymal calcifications and revealed multiple hepatosplenic microabscesses of fungal etiology. Conclusions: Chronic calcifying pancreatitis is a complex clinical entity that can lead to secondary diabetes due to progressive destruction of the pancreatic parenchyma. Protein malnutrition, caused by malabsorption syndrome, immune cell dysfunction, and a high glucose environment caused by diabetes mellitus, may create a state of immunodeficiency, predisposing the patient to opportunistic infections

Pathogenic Copy Number Variations Involved in the Genetic Etiology of Syndromic and Non-Syndromic Intellectual Disability—Data from a Romanian Cohort

The investigation of unexplained global developmental delay (GDD)/intellectual disability (ID) is challenging. In low resource settings, patients may not follow a standardized diagnostic process that makes use of the benefits of advanced technologies. Our study aims to explore the contribution of chromosome microarray analysis (CMA) in identifying the genetic etiology of GDD/ID. A total of 371 Romanian patients with syndromic or non-syndromic GDD/ID, without epilepsy, were routinely evaluated in tertiary clinics. A total of 234 males (63.07%) and 137 (36.93%) females, with ages ranging from 6 months to 40 years (median age of 5.5 years), were referred for genetic diagnosis between 2015 and 2022; testing options included CMA and/or karyotyping. Agilent Technologies and Oxford Gene Technology CMA workflows were used. Pathogenic/likely pathogenic copy number variations (pCNVs) were identified in 79 patients (21.29%). Diagnosis yield was comparable between mild ID (17.05%, 22/129) and moderate/severe ID 23.55% (57/242). Higher rates were found in cases where facial dysmorphism (22.97%, 71/309), autism spectrum disorder (ASD) (19.11%, 26/136) and finger anomalies (20%, 27/96) were associated with GDD/ID. GDD/ID plus multiple congenital anomalies (MCA) account for the highest detection rates at 27.42% (17/62). pCNVs represent a significant proportion of the genetic causes of GDD/ID. Our study confirms the utility of CMA in assessing GDD/ID with an uncertain etiology, especially in patients with associated comorbidities