Anne-Marie Laberge

CHU Sainte-Justine · Department of Pediatrics

Following its introduction to the market in 2011, the rapid spread of noninvasive prenatal testing (NIPT) was driven by commercial developers of the technology. The numerous benefits it offers are recognized by users and clinicians, but its introduction also raises several concerns regarding ethical, social, legal, and policy implications. This cha...

Parents of children with genetically determined leukoencephalopathies play a major role in their children's health care. We sought to gain a better understanding of their experience with the public health care system in Quebec, Canada, to obtain suggestions for improving their services, and to identify modifiable factors to improve their quality of...

Non-invasive prenatal testing’s (NIPT) potential to screen for a wide range of conditions is receiving growing attention. This study explores Canadian healthcare professionals’ perceptions towards NIPT’s current and possible future uses, including paternity testing, sex determination, and fetal whole genome sequencing. Semi-structured interviews we...

Parents of children with genetically determined leukoencephalopathies play a major role in their children's health care. Because of the COVID-19 pandemic, many health care services were suspended, delayed or delivered remotely with telemedicine. We sought to explore the experience of parents of children with genetically determined leukoencephalopat...

(1) To explore individual and family characteristics related to anthropometric and cardiometabolic health indicators and (2) examine whether characteristics that correlate with cardiometabolic health indicators differ across severity of obesity at time of entry to Canadian pediatric weight management clinics. We conducted a cross-sectional analysis...

L’implantation d’une nouvelle technologie est une étape de la translation d’une découverte vers une application clinique. De nombreux modèles ont été proposés pour étudier une telle translation ; celui de Goering, Holland et Kelley met de l’avant des priorités qui résonnent avec la bioéthique. Nous proposons l’application d’un outil issu des scienc...

Our study purpose was to determine the prevalence of metabolically healthy obesity (MHO) and examine factors associated with MHO in children with obesity. This cross-sectional study was a secondary, exploratory analysis of data that included 2-17 years old with a body mass index (BMI) ≥85th percentile from the CANadian Pediatric Weight management R...

Purpose and scope The aim of this position statement is to provide recommendations for Canadian healthcare professionals regarding the use of genome-wide sequencing (GWS) in the context of diagnostic testing of the fetus during pregnancy. This statement was developed to facilitate clinical translation of GWS as a prenatal diagnostic test and the de...

Background and objective: Children with inherited metabolic diseases often require complex and highly specialized care. Patient and family-centered care can improve health outcomes that are important to families. This study aimed to examine experiences of family caregivers (parents/guardians) of children diagnosed with inherited metabolic diseases...

Background: Clinical practice guidelines for pediatric weight management highlight the importance of family-based behavioral strategies to enhance health behaviors. Little is known, however, of how clinics implement these programs. The study objectives were to (1) describe how Canadian pediatric weight management clinics deliver care and (2) evalua...

Leukodystrophies, genetic neurodevelopmental and/or neurodegenerative disorders of cerebral white matter result from impaired myelin homeostasis and metabolism. Numerous genes have been implicated in these heterogeneous disorders; however, many individuals remain without a molecular diagnosis. Using whole exome sequencing, biallelic variants in LSM...

The Saguenay–Lac-Saint-Jean (SLSJ) region located in the province of Quebec was settled in the 19th century by pioneers issued from successive migration waves starting in France in the 17th century and continuing within Quebec until the beginning of the 20th century. The genetic structure of the SLSJ population is considered to be the product a tri...

Recent studies have identified suggestive prenatal features of RASopathies (e.g., increased nuchal translucency [NT], cystic hygroma [CH], hydrops, effusions, congenital heart diseases [CHD], polyhydramnios, renal anomalies). Our objective is to clarify indications for RASopathy prenatal testing. We compare genotype distributions between pre- and p...

Background In the near future, developments in non-invasive prenatal testing (NIPT) may offer couples the opportunity to expand the range of genetic conditions tested with this technology. This possibility raises a host of ethical and social concerns, such as the type of information (medical vs. non-medical information) that couples might be expose...

Background Noninvasive prenatal testing (NIPT) provides important benefits yet raises ethical concerns. We surveyed Canadian pregnant women and their partners to explore their views regarding pressure to test and terminate a pregnancy, as well as other societal impacts that may result from the routinization of NIPT. Methods A questionnaire was off...

Objective: While rare variants in the COL5A1 gene have been associated with classical Ehlers-Danlos syndrome and rarely with arterial dissections, recurrent variants in COL5A1 underlying a systemic arteriopathy have not been described. Monogenic forms of multifocal fibromuscular dysplasia (mFMD) have not been previously defined. Approach and Resul...

Background: The clinical introduction of non-invasive prenatal testing for fetal aneuploidies is currently transforming the landscape of prenatal screening in many countries. Since it is noninvasive, safe and allows the early detection of abnormalities, NIPT expanded rapidly and the test is currently commercially available in most of the world. As...

Our objectives were to describe fetal cases of vertebral defects (VD), assess the diagnostic yield of fetal chromosomal analysis for VD and determine which investigations should be performed when evaluating fetal VD. We performed a retrospective chart review for fetuses with VD seen between 2006 and 2015. Cases were identified from CHU Sainte‐Justi...

When evidence thresholds are met, adopting healthcare innovations should add value, and this is forgone when evidence is not translated into practice. Activities that are not supported by evidence lead to ineffective or unnecessary care, or harm, poor outcomes, and low-value healthcare. This article provides an overview of implementation science, w...

Genomic sequencing and multigene panel tests are moving rapidly into clinical practice for a range of indications, but the evidence to guide appropriate use is currently limited. Well-crafted advice is needed to reduce unjustified practice variation, minimize risk of error and harm to patients, and encourage best practices. In the absence of defini...

Background: Disease severity in paediatric obesity is usually defined using the body-mass index (BMI). Although informative at the population level, its usefulness on an individual level has limitations. The use of a clinical staging system-Edmonton Obesity Staging System for Pediatrics (EOSS-P)-in identifying health risk has been proposed. This s...

Background We describe early health services utilization for children diagnosed with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency through newborn screening in Ontario, Canada, relative to a screen negative comparison cohort. Methods Eligible children were identified via newborn screening between April 1, 2006 and March 31, 2010. Age-strat...

Objective: This study sought to assess Canadian pregnant women's and their partners' preferences for information about non-invasive prenatal testing (NIPT). Methods: Pregnant women and their partners across Canada were surveyed as part of the Personalized Genomics for prenatal Aneuploidy Screening Using maternal blood (PEGASUS) study. Results:...

The ryanodine receptor 1 (RYR1) is a calcium release channel essential for excitation‐contraction coupling in the sarcoplasmic reticulum of skeletal muscles. Dominant variants in the RYR1 have been well associated with the known pharmacogenetic ryanodinopathy and malignant hyperthermia. With the era of next‐generation gene sequencing and growing nu...

Background: Canadian policies regarding the implementation and public coverage of non-invasive prenatal testing (NIPT) are heterogeneous and shifting, with NIPT being publicly covered for high-risk pregnancies in some provinces, but not others. Such a diverse and evolving policy landscape provides fertile ground for examining the preferences of pre...

Parents’ understanding/expectations regarding genetic testing for children with developmental disorders were explored. Within a month of testing, interviews were conducted with 57 parents. Many (74%) could not recall the nature of testing. Parents expected genetic testing to have positive impacts for the child (93%) and the family (98%), mainly to...

Objectives: To assess paediatricians' use of genetic testing for children with global developmental delay (GDD). Study design: We developed and piloted a questionnaire assessing the use of genetic tests in children with GDD and awareness of relevant guidelines. All practicing Quebec paediatricians were contacted. Paediatricians who did not evalu...

The use of pre-implantation genetic diagnosis (PGD) is increasing as the list of indications it can test for constantly expands. This raises new challenges for clinicians and prospective parents regarding possible uses and calls for guidance. Policy approaches towards PGD vary greatly worldwide. The 2004 Canadian Assisted Human Reproduction Act doe...

Objective: To assess obstetric and aortic outcomes in women with Marfan Syndrome according to aortic root diameter, in view of recommendations for caesarean delivery when the aortic root diameter is ≥40 mm in the 2010 American guidelines versus >45 mm in the 2011 European guidelines. Study design: In this retrospective cohort study conducted at...

Background: There is increasing recognition of the value of "real-world evidence" in evaluating health care services. Registry-based, observational studies conducted in clinical settings represent a relevant model to achieve this directive. Starting in 2010, we undertook a longitudinal, observational study (the CANadian Pediatric Weight management...

The transcription factor BCL11B is essential for development of the nervous and the immune system, and Bcl11b deficiency results in structural brain defects, reduced learning capacity, and impaired immune cell development in mice. However, the precise role of BCL11B in humans is largely unexplored, except for a single patient with a BCL11B missense...

Purpose: We aimed to assess the definition of actionability of secondary findings in childhood, using a screening framework. Methods: For 31 disorders on the American College of Medical Genetics and Genomics SF v.2.0 list, World Health Organization screening criteria were applied to assess actionability in childhood. Results: The age of onset...

Noninvasive prenatal testing (NIPT), based on the detection of cell-free fetal DNA in maternal blood, has transformed the landscape of prenatal care by offering clinical benefits (noninvasive, high specificity and sensitivity, early detection of abnormalities) compared to existing prenatal screening tests. NIPT has expanded rapidly and is currently...

Aim: Investigate paediatricians' expectations and perspectives of genetic testing for children with developmental disorders. Methods: Paediatricians working in a developmental clinic were surveyed each time they ordered a chromosomal microarray (CMA) for a child with developmental disorders. Clinical charts were reviewed. Results were analysed u...

Although NGS technologies are well-embedded in the clinical setting for identification of genetic causes of disease, guidelines issued by professional bodies are inconsistent regarding some aspects of reporting results. Most recommendations do not give detailed guidance about whether variants of uncertain significance (VUS) should be reported by la...

Genetic screening is the process of systematically evaluating a defined population for genetic conditions or predispositions, in the hope of providing benefit to those with a positive result. With advances in sequencing technology, genetic screening is moving from phenotype-based to genotype-based testing. Although sequencing technology offers expa...

Objectives: Describe the experience of carrier couples identified through this program. Methods: Semi-structured interviews were performed with carrier couples. Thematic analysis of interview transcripts was done to identify emerging themes. Results: Interviews were done with 15 carrier couples (56% response rate). Carrier couples had little k...

Background There is no consensus in the literature regarding the impact of false positive newborn screening results on early health care utilization patterns. We evaluated the impact of false positive newborn screening results for medium-chain acyl-CoA dehydrogenase deficiency (MCADD) in a cohort of Ontario infants. Methods The cohort included all...

Background We sought to understand the experiences of parents/caregivers of children with inherited metabolic diseases (IMD) in order to inform strategies for supporting patients and their families. We investigated their experiences regarding the management of disease, its impact on child and family life, and interactions with the health care syste...

Objectives The long-term health system impact of phenylketonuria (PKU) is not well-understood. Using population-based newborn screening (NBS) and health care administrative data, we describe health care use among Ontario children with PKU in the first few years of life, relative to an unaffected cohort. Methods Of infants who underwent NBS for PKU...

Objectives Many newborn screening (NBS) programs across the world recently celebrated 50 years of important health benefits for babies affected with rare diseases. Though, the impact of false-positive NBS on health services use (HSU) remains poorly understood. Ontario is Canada’s most populous province with 140,000 births per year and universal, pu...

Background In 2012, the Montreal Heart Institute started an integrated multidisciplinary clinic for adults referred for suspicion of Marfan syndrome or other connective tissue disorders at risk of aortic disease. A heart team (cardiologist specialised in adult congenital heart disease, heart surgeons specialised in aortic surgery) and a genetics te...

Background Pure distal 1q trisomy is rare and there is limited information on genotype-phenotype correlation. The common 1q trisomy phenotype attributed to the 1q42qter segment is based on a small number of patients and consists of small for gestational age, developmental delay, macrocephaly, dysmorphic features and heart defects. Objective To clar...

Joubert syndrome (JBTS) is a primarily autosomal-recessive disorder characterized by a distinctive mid-hindbrain and cerebellar malformation, oculomotor apraxia, irregular breathing, developmental delay, and ataxia. JBTS is a genetically heterogeneous ciliopathy. We sought to characterize the genetic landscape associated with JBTS in the French Can...

The knowledge surrounding the genetic etiologies of familial aortopathies and familial thoracic aortic aneurysms and dissections has greatly expanded over the past few years. However, despite these advances, the underlying molecular etiology remains unidentified in most families with nonsyndromic familial aortopathies, and in a subset of families w...

Advances in genetic technology over the last 10 years have revealed the polygenic basis of thoracic aortic aneurysm and thoracic aortic acute dissection (TAAD) in a sub-set of patients. There is mounting evidence to show that clinical risk stratification for aneurysmal dilatation and acute dissection can be based on genotype for some of the known g...

Patient-centered health care for children with inborn errors of metabolism (IEM) and their families is important and requires an understanding of patient experiences, needs, and priorities. IEM-specific patient groups have emerged as important voices within these rare disease communities and are uniquely positioned to contribute to this understandi...

The aim of this Position Statement is to provide recommendations for Canadian medical geneticists, clinical laboratory geneticists, genetic counsellors and other physicians regarding the use of genome-wide sequencing of germline DNA in the context of clinical genetic diagnosis. This statement has been developed to facilitate the clinical translatio...

Deficiency of pyridox(am)ine 5'-phosphate oxidase (PNPO, OMIM 610090) is a treatable autosomal recessive inborn error of metabolism. Neonatal epileptic encephalopathy and a low cerebrospinal fluid (CSF) pyridoxal 5'-phosphate level are the reported hallmarks of PNPO deficiency, but its clinical and biochemical spectra are not fully known. A girl bo...

What's already known about this topic? Fibrodysplasia ossificans progressiva (FOP) (MIM: 135100) is a very rare autosomal dominant condition with a prevalence of 1:2,000,000. The clinical picture is characterized by congenital malformations of the great toes and progressive disabling heterotopic ossification. The genetic explanation is an activatin...

Introduction: Nearly all children in Canada with an inherited metabolic disease (IMD) are treated at one of the country's Hereditary Metabolic Disease Treatment Centres. We sought to understand the system of care for paediatric IMD patients in Canada in order to identify sources of variation and inform future research priorities. Methods: Treatm...

Background: Improvements in health care for children with chronic diseases must be informed by research that emphasizes outcomes of importance to patients and families. To support a program of research in the field of rare inborn errors of metabolism (IEM), we conducted a broad scoping review of primary studies that: (i) focused on chronic pediatri...

Brain tumors are the second most common cause of cancer in children and the leading cause of morbidity and mortality. A significant number of these cancers have specific genetic events which could be traced to the germline. As a result, these cancer predisposition syndromes are seen in children with brain tumors in much higher frequency than other...

Objectives: Pyrroline-5-carboxylate synthase catalyzes the bio-synthesis of proline, ornithine and arginine. Its deficiency (P5CSD) is characterized by neurological and connective tissue abnormalities. Less than 10 cases have been reported, with abnormal amino acid profile in only one family. Two new cases will be described here. Methods: A literat...

Background Over recent decades, the prevalence of pediatric obesity has increased markedly in developed and developing countries, and the impact of obesity on health throughout the lifespan has led to urgent calls for action. Family-based weight management interventions that emphasize healthy lifestyle changes can lead to modest improvements in wei...

BACKGROUND Genetic testing for developmental problems is routine. Because of increased performance, microarray-based Comparative Genomic Hybridization (CGH) has replaced karyotyping. Up to 30% of children with developmental problems have an abnormal CGH. Using CGH results to establish diagnosis and prognosis may be complex. OBJECTIVES Examine the...

OBJECTIVES To broadly but systematically review and identify patient- and family-oriented outcome constructs and self-administered measures relevant to inborn errors of metabolism (IEM). CONCLUSIONS Studies measuring patient- and family-oriented outcomes for chronic, complex pediatric disease emphasize mental health and quality of life; further re...

Early detection of cystic fibrosis (CF) by newborn screening (NBS) reduces the rate of avoidable complications. NBS protocols vary by jurisdiction and the cost effectiveness of these different protocols is debated. To compare the cost effectiveness of various CF NBS options. A Markov model was built to simulate the cost effectiveness of various CF-...

Background: Early detection of cystic fibrosis (CF) by newborn screening (NBS) reduces the rate of avoidable complications. NBS protocols vary by jurisdiction and the cost effectiveness of these different protocols is debated. Objective: To compare the cost effectiveness of various CF NBS options. Methods: A Markov model was built to simulate the c...

Available from: http://ww2.aievolution.com/acm1301/index.cfm?do=abs.viewAbs&abs=1312