Behavioural phenotypes associated with specific genetic disorders: evidence from a population-based study of people with Prader-Willi syndrome

2002 ◽  
Vol 33 (1) ◽  
pp. 141-153 ◽  
Author(s):  
A. J. HOLLAND ◽  
J. E. WHITTINGTON ◽  
J. BUTLER ◽  
T. WEBB ◽  
H. BOER ◽  
...  
Keyword(s):  
Learning Disabilities ◽  
Genetic Disorders ◽  
Genetic Disorder ◽  
Genetic Diagnosis ◽  
Learning Disabled ◽  
Structured Interview ◽  
Prader Willi Syndrome ◽  
Multiple Sources ◽  
Behavioural Phenotype ◽  
Severe Problem

Background. Prader-Willi syndrome (PWS) is a genetic disorder resulting in obesity, short stature, cryptorchidism, learning disabilities (mental retardation) and severe neonatal hypotonia. Associated with the syndrome are a number of behaviours that are sufficiently distinctive that the syndrome is considered to have a specific ‘behavioural phenotype’.Methods. Through multiple sources we attempted to identify all people with PWS living in one region in the UK. This cohort was augmented by people with PWS from other regions, and a contrast group of people with learning disabilities of varied aetiologies. The main carers were interviewed, using structured and semi-structured interview schedules, to establish the presence and severity of specific behaviours, and PWS diagnostic criteria. The intellectual functioning and attainments of all were determined. Blood samples were obtained for genetic diagnosis from all consenting participants.Results. Although excessive eating was recognized as a potentially severe problem in those with PWS, it was almost universally controlled by food restriction, and therefore not seen as a ‘problem behaviour’. Those with PWS differed from a learning disabled group of other aetiologies in the prevalence rates of skin picking, temper tantrums, compulsive behaviours and mood fluctuations, and also in the profile of their adaptive behaviours.Conclusions. The study confirms the distinct behavioural phenotype of PWS. Specific behaviours occurred significantly more frequently in PWS, compared with an age and BMI matched learning disabled comparison group. A factor analysis of the behaviours involved resulted in three factors that we hypothesized to be independent, and to arise from different mechanisms.

scholarly journals Manifestaciones clínicas asociadas al síndrome de Prader-Willi: Revisión Descriptiva

2018 ◽  
Vol 30 (1) ◽  
Author(s):  
Jesús Dzul Hernández ◽  
Rossana Borges Cauich ◽  
Montserrat Rodríguez Huchim ◽  
Guillermo Pérez Correa ◽  
Nina Mendez-Dominguez ◽  
...  
Keyword(s):  
Genetic Disorders ◽  
Genetic Disorder ◽  
Clinical Manifestations ◽  
Low Frequency ◽  
Signs And Symptoms ◽  
Diagnostic Techniques ◽  
Prader Willi Syndrome ◽  
Specific Patient ◽  
Calidad De Vida ◽  
Wide Range

RESUMEN El síndrome de Prader–Willi (SPW) es un trastorno genético, que afecta el neurodesarrollo que, a pesar de su baja frecuencia, merece ser considerado como un trastorno de relevancia clínica al ser la causa más frecuente de obesidad de origen genético. Las manifestaciones clínicas que derivan de SPW tienen origen en la desregulación hipotalámica, por lo cual, comprendiendo la trascendencia e implicación de la afectación hipotalámica, puede comprenderse la amplia gama de manifestaciones que pueden presentarse con severidad variable y cuyas complicaciones su vez la afectación a la salud y socialización a largo plazo afectando la calidad de vida de los pacientes con SPW. Un diagnóstico preciso permite distinguir este síndrome de otros trastornos genéticos y de otras patologías que afectan la función hipotalámica a la vez que permite estimar la gravedad de las manifestaciones y el riesgo de repetición en una misma familia. Por ello, la presente revisión descriptiva se ofrece con el objetivo de describir las manifestaciones clínicas del síndrome de Prader-Willi que orienten la sospecha clínica, las similitudes que presenta este síndrome con otros trastornos, así como presentar las técnicas de diagnóstico disponibles que permiten orientar adecuadamente el abordaje de los pacientes y facilitar su manejo integral oportunamente.ABSTRACT: Prader-Willi syndrome (PWS) is a genetic disorder that affects neurodevelopment, which, despite its low frequency, deserves to be considered a clinically relevant disorder since it is the most frequent cause of genetically derived obesity. The clinical manifestations that derive from SPW correlate to those from a hypothalamic dysregulation, so that, understanding the importance and implication of the hypothalamic involvement, the wide range of manifestations that can present with variable severity and whose complications in turn affect the health can be understood. and long-term socialization affecting the quality of life of patients with PWS. An accurate diagnosis can discriminate this syndrome from other genetic disorders and from non-genetic pathologies that affect hypothalamic function, while also allowing to estimate the severity in a specific patient and the risk of repetition in other family members. Therefore, the present descriptive review is aimed to describe the clinical manifestations of Prader-Willi syndrome to guide the clinical diagnosis; the signs and symptoms that can differentiate this syndrome from other disorders, as well as presenting a description of the actual diagnostic techniques that can allow a prompt and precise diagnosis, and thus, translate in a comprehensive and timely approach of the patients with PWS.

scholarly journals Turkish teachers' opinions of the problems they face in the classroom of students with learning disabilities

2015 ◽  
Vol 5 (5) ◽  
pp. 509-532 ◽  
Author(s):  
İbrahim Dadandı ◽  
Pakize Urfalı Dadandı
Keyword(s):  
Learning Disabilities ◽  
Language Skills ◽  
Learning Disabled ◽  
Structured Interview ◽  
Individualized Education Programs ◽  
Students With Learning Disabilities ◽  
Teaching Language ◽  
Basic Language ◽  
Service Training ◽  
Training Courses

The aim of this study is to identify problems encountered by Turkish teachers who have students with learning disabilities. Following the qualitative research, data in this study were collected through semi-structured interview. The study was conducted with 10 Turkish teachers who have students with learning disabilities. The data were analyzed using content analysis. In the study, it was found out that Turkish teachers encountered problems in the implementation of individualized education programs for students with learning disabilities in getting those students gain basic language skills, in the interaction process of these students' class and in communicating with their parents. To increase the effectiveness of the implementations, some suggestions such as increasing the special education qualification of teachers through in-service training courses, organizing seminars for parents, and conducting further researches that examines the effectiveness of computer-aided teaching methods in teaching language skills to learning disabled students were proposed.

scholarly journals Genetic disorder prenatal diagnosis and pregnancy termination practices among high consanguinity population, Saudi Arabia

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sayed AbdulAzeez ◽  
Nourah H. Al Qahtani ◽  
Noor B. Almandil ◽  
Amani M. Al-Amodi ◽  
Sumayh A. Aldakeel ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Prenatal Diagnosis ◽  
Family History ◽  
Pregnancy Termination ◽  
Genetic Disorders ◽  
Genetic Disorder ◽  
Genetic Diagnosis ◽  
Limiting Factors ◽  
Good Opportunity ◽  
Awareness Campaigns

AbstractThe prevalence of consanguineous marriage and genetic disorders are high in Saudi Arabia. There were records on the practices of Saudis toward prenatal diagnosis (PND) and termination of pregnancy (TOP), however the sample sizes are small. This study has targeted the Saudi Arabian community and family history of genetic disorders to determine the practices toward PND and TOP. The cross-sectional survey was conducted among Saudis (n = 2761) to determine their practices toward reproductive-decision making. Regression analysis was conducted to identify the association of the limiting factors, relative merits and family history on the outcomes. Total of 2507 participants returned completed questionnaire. The practice towards PND (68%) were more favorable than TOP (33%). PND was found to be a good opportunity for early diagnosis and gives parent’s choice. Education, history with affected baby, prior knowledge and religious belief were significant deciding factors of PND and TOP. Down syndrome (n = 161) and sickle cell anemia (n = 152) were commonly available genetic disorder among participant’s family. Respondents with autistic cases in their family have higher acceptance rate for TOP. Non-consanguineous are more willing to consider TOP than consanguineous. Participants with abnormal fetus, aged of > 36 years, married and educated Saudis were more likely consider TOP. Though, religion is the most influencing factor for not accepting TOP, comparatively willingness to PND and TOP have increased recently. Awareness campaigns about PND and TOP may increase the chances of accepting prenatal genetic diagnosis.

scholarly journals Specific Dietary Components and Gut Microbiota Composition are Associated with Obesity in Children and Adolescents with Prader–Willi Syndrome

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1063 ◽  
Author(s):  
Sonika Garcia-Ribera ◽  
Montse Amat-Bou ◽  
Eric Climent ◽  
Marina Llobet ◽  
Empar Chenoll ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Children And Adolescents ◽  
Weight Status ◽  
Genetic Disorder ◽  
Standard Deviation Score ◽  
Genetic Diagnosis ◽  
Normal Weight ◽  
Prader Willi Syndrome ◽  
Microbiota Composition ◽  
16S Sequencing

Prader–Willi syndrome is a rare genetic disorder associated with impaired body composition, hyperphagia, and excessive weight gain. Strict dietary restrictions from an early age is crucial to prevent or delay the early onset of obesity, which is the main driver of comorbidities in these patients. The aim of this study was to identify dietary and gut microbiota components closely linked to weight status of these patients. We studied a cohort of children and adolescents with genetic diagnosis of Prader–Willi syndrome (N = 31), in which we determined adiposity by Dual-energy X-ray absorptiometry (DXA) and dietary composition with 4-day food records. Furthermore, we obtained fecal samples to assess microbiota composition by 16S sequencing. Multivariate regression models showed that body mass index standard deviation score (BMI-SDS) and body fat mass were directly associated with saturated fat intake and meat consumption, and inversely associated with fruit consumption. Furthermore, the gut microbiome from normal weight patients was characterized by higher phylogenetic diversity compared to those overweight or obese, with differential abundance of several genera, including Alistipes, Klebsiella, and Murimonas. Notably, Alistipes abundance was inversely correlated to adiposity, lipid and glucose homeostasis parameters, and meat intake. Our results suggest that limiting meat and increasing fruit intake might be beneficial for body weight management in children and adolescents with Prader–Willi syndrome.

What Potent Blood: Non-Invasive Prenatal Genetic Diagnosis and the Transformation of Modern Prenatal Care

2007 ◽  
Vol 33 (1) ◽  
pp. 9-53 ◽  
Author(s):  
Carolyn Jacobs Chachkin
Keyword(s):  
Genetic Disorders ◽  
Genetic Disorder ◽  
Genetic Material ◽  
Genetic Diagnosis ◽  
Prenatal Testing ◽  
Maternal Blood ◽  
Non Invasive ◽  
Tay Sachs Disease ◽  
Promising Solution ◽  
Low Levels

What potent blood hath modest May,What fiery force the earth renews,The wealth of forms, the flush of hues ….—Ralph Waldo EmersonSomeday soon, virtually any pregnant woman will be able to learn — with 98-99% accuracy — whether her fetus has contracted a serious genetic disorder by undergoing nothing more than an inexpensive, non-invasive blood test. For years, scientists have sought a method of prenatal testing that could boast both high levels of accuracy and low levels of risk. The most promising solution lies in an exciting recent discovery: tiny quantities of fetal cells and DNA cross over into the mother's bloodstream during pregnancy. If the fetal genetic material can be successfully isolated from the maternal blood, it can be used to diagnose a number of genetic disorders, such as Down Syndrome, cystic fibrosis, Tay-Sachs disease, and sickle cell anemia. Indeed, researchers have spent the last decade developing ways to accomplish this.

scholarly journals Congenital anomalies and genetic disorders in neonates and infants: a single-center observational cohort study

2021 ◽  
Author(s):  
A. Marouane ◽  
R. A. C. M. Olde Keizer ◽  
G. W. J. Frederix ◽  
L. E. L. M. Vissers ◽  
W. P. de Boode ◽  
...  
Keyword(s):  
Congenital Anomalies ◽  
Neonatal Intensive Care ◽  
Diagnostic Yield ◽  
Genetic Disorders ◽  
Genetic Disorder ◽  
Genetic Diagnosis ◽  
Neonatal Intensive Care Units ◽  
Academic Level ◽  
Observational Cohort ◽  
Neonates And Infants

AbstractNeonates with genetic disorders or congenital anomalies (CA) contribute considerably to morbidity and mortality in neonatal intensive care units (NICUs). The objective of this study is to study the prevalence of genetic disorders in an academic level IV NICU. We retrospective collected and analyzed both clinical and genetic data of all 1444 infants admitted to the NICU of the Radboudumc (October 2013 to October 2015). Data were collected until infants reached at least 2 years of age. A total of 13% (194/1444) of the patients were genetically tested, and 32% (461/1444) had a CA. A total of 37% (72/194) had a laboratory-confirmed genetic diagnosis. In 53%, the diagnosis was made post-neonatally (median age = 209 days) using assays including exome sequencing. Exactly 63% (291/461) of the patients with CA, however, never received genetic testing, despite being clinically similar those who did.Conclusions: Genetic disorders were suspected in 13% of the cohort, but only confirmed in 5%. Most received their genetic diagnosis in the post-neonatal period. Extrapolation of the diagnostic yield suggests that up to 6% of our cohort may have remained genetically undiagnosed. Our data show the need to improve genetic care in the NICU for more inclusive, earlier, and faster genetic diagnosis to enable tailored management. What is Known:• Genetic disorders are suspected in many neonates but only genetically confirmed in a minority.• The presence of a genetic disorder can be easily missed and will often lead to a diagnostic odyssey requiring extensive evaluations, both clinically and genetically. What is New:• Different aspects of the clinical features and uptake of genetic test in a NICU cohort.• The need to improve genetic care in the NICU for more inclusive, earlier, and faster genetic diagnosis to enable tailored management.

scholarly journals Study Design and Baseline Characteristics of the CARDINAL Trial: A Phase 3 Study of Bardoxolone Methyl in Patients with Alport Syndrome

2021 ◽  
pp. 1-10
Author(s):  
Glenn M. Chertow ◽  
Gerald B. Appel ◽  
Sharon Andreoli ◽  
Sripal Bangalore ◽  
Geoffrey A. Block ◽  
...  
Keyword(s):  
Kidney Function ◽  
Alport Syndrome ◽  
Genetic Disorder ◽  
Geometric Mean ◽  
Genetic Diagnosis ◽  
Significant Loss ◽  
The European Union ◽  
Phase 3 ◽  
Double Blind ◽  
Histologic Diagnosis

<b><i>Introduction:</i></b> Alport syndrome is a rare genetic disorder that affects as many as 60,000 persons in the USA and a total of 103,000 persons (&#x3c;5 per 10,000) in the European Union [1, 2]. It is the second most common inherited cause of kidney failure and is characterized by progressive loss of kidney function that often leads to end-stage kidney disease. Currently, there are no approved disease-specific agents for therapeutic use. We designed a phase 3 study (CARDINAL; NCT03019185) to evaluate the safety, tolerability, and efficacy of bardoxolone methyl in patients with Alport syndrome. <b><i>Methods:</i></b> The CARDINAL phase 3 study is an international, multicenter, double-blind, placebo-controlled, randomized registrational trial. Eligible patients were of ages 12–70 years with confirmed genetic or histologic diagnosis of Alport syndrome, eGFR 30–90 mL/min/1.73 m<sup>2</sup>, and urinary albumin to creatinine ratio (UACR) ≤3,500 mg/g. Patients with B-type natriuretic peptide values &#x3e;200 pg/mL at baseline or with significant cardiovascular histories were excluded. Patients were randomized 1:1 to bardoxolone methyl or placebo, with stratification by baseline UACR. <b><i>Results:</i></b> A total of 371 patients were screened, and 157 patients were randomly assigned to receive bardoxolone methyl (<i>n</i> = 77) or placebo (<i>n</i> = 80). The average age at screening was 39.2 years, and 23 (15%) were &#x3c;18 years of age. Of the randomized population, 146 (93%) had confirmed genetic diagnosis of Alport syndrome, and 62% of patients had X-linked mode of inheritance. Mean baseline eGFR was 62.7 mL/min/1.73 m<sup>2</sup>, and the geometric mean UACR was 141.0 mg/g. The average annual rate of eGFR decline prior to enrollment in the study was −4.9 mL/min/1.73 m<sup>2</sup> despite 78% of the patient population receiving ACE inhibitor (ACEi) or ARB therapy. <b><i>Discussion/Conclusion:</i></b> CARDINAL is one of the largest interventional, randomized controlled trials in Alport syndrome conducted to date. Despite the use of ACEi or ARB, patients were experiencing significant loss of kidney function prior to study entry.

scholarly journals Endocrine Dysfunction in Prader-Willi Syndrome: A Review with Special Reference to GH

2001 ◽  
Vol 22 (6) ◽  
pp. 787-799 ◽  
Author(s):  
Pia Burman ◽  
E. Martin Ritzén ◽  
Ann Christin Lindgren
Keyword(s):  
Replacement Therapy ◽  
Lean Body Mass ◽  
Body Mass ◽  
Genetic Disorder ◽  
Hormone Replacement ◽  
Hypogonadotropic Hypogonadism ◽  
Endocrine Disorders ◽  
Prader Willi Syndrome ◽  
Gh Treatment ◽  
Pituitary Dysfunction

Abstract Prader-Willi syndrome is a genetic disorder occurring in 1 in 10,000–16,000 live-born infants. In the general population, approximately 60 people in every 1,000,000 are affected. The condition is characterized by short stature, low lean body mass, muscular hypotonia, mental retardation, behavioral abnormalities, dysmorphic features, and excessive appetite with progressive obesity. Furthermore, morbidity and mortality are high, probably as a result of gross obesity. Most patients have reduced GH secretory capacity and hypogonadotropic hypogonadism, suggesting hypothalamic-pituitary dysfunction. Replacement of GH and/or sex hormones may therefore be beneficial in Prader-Willi syndrome, and several clinical trials have now evaluated GH replacement therapy in affected children. Results of GH treatment have been encouraging: improved growth, increased lean body mass, and reduced fat mass. There was also some evidence of improvements in respiratory function and physical activity. The long-term benefits of GH treatment are, however, still to be established. Similarly, the role of sex hormone replacement therapy needs to be clarified as few data exist on its efficacy and potential benefits. In summary, Prader-Willi syndrome is a disabling condition associated with GH deficiency and hypogonadism. More active treatment of these endocrine disorders is likely to benefit affected individuals.

GENETIC DISORDER OF THE ENDOCRINE GLANDS, by David L. Rimoin, M.D., Ph.D., R. Neil Schimke, M.D. St. Louis: The C. V. Mosby Company, 1971, 383 pp., $32.50

PEDIATRICS ◽  
1972 ◽  
Vol 49 (5) ◽  
pp. 798-798
Author(s):  
S. Douglas Frasier
Keyword(s):  
Genetic Disorders ◽  
Genetic Disorder ◽  
Endocrine Glands

The authors present this book as an attempt to catalogue the known genetic disorders of the endocrine glands. They have succeeded admirably. Each chapter begins with a brief description of the embryology and physiology of the gland under discussion. If there are weaknesses in this presentation, they are excusable in the light of the authors' main purpose. Embryology and physiology are followed by a catalogue of genetic disorders which are associated with altered function of that gland.

Learning Disabilities and Reading: Instructional Recommendations from Current Research

1983 ◽  
Vol 50 (3) ◽  
pp. 230-240 ◽  
Author(s):  
Rena B. Lewis
Keyword(s):  
Learning Disabilities ◽  
Instructional Strategies ◽  
Teacher Effectiveness ◽  
Direct Instruction ◽  
Learning Disabled ◽  
Cognitive Resources ◽  
Students With Learning Disabilities ◽  
Teaching Of Reading ◽  
Education Of Students

This review of research addresses the teaching of reading, one of the most common concerns in the education of students with learning disabilities. First, past conceptualizations of the condition of learning disabilities are considered, then rejected in favor of the notion that learning disabled individuals are characterized by a failure to deploy cognitive resources effectively. Next, recent research on teacher effectiveness and the technology of direct instruction is examined in relation to current understandings of the nature and treatment of learning disabilities. Finally, empirically based instructional strategies for the teaching of reading to the learning disabled are suggested.

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