Psychiatric Illness and Regression in Individuals with Phelan- Mcdermid Syndrome
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A Brazilian Cohort of Individuals with Phelan-Mcdermid Syndrome
Samogy-Costa et al. Journal of Neurodevelopmental Disorders (2019) 11:13 https://doi.org/10.1186/s11689-019-9273-1 RESEARCH Open Access A Brazilian cohort of individuals with Phelan-McDermid syndrome: genotype- phenotype correlation and identification of an atypical case Claudia Ismania Samogy-Costa1†, Elisa Varella-Branco1†, Frederico Monfardini1, Helen Ferraz2, Rodrigo Ambrósio Fock3, Ricardo Henrique Almeida Barbosa3, André Luiz Santos Pessoa4,5, Ana Beatriz Alvarez Perez3, Naila Lourenço1, Maria Vibranovski1, Ana Krepischi1, Carla Rosenberg1 and Maria Rita Passos-Bueno1* Abstract Background: Phelan-McDermid syndrome (PMS) is a rare genetic disorder characterized by global developmental delay, intellectual disability (ID), autism spectrum disorder (ASD), and mild dysmorphisms associated with several comorbidities caused by SHANK3 loss-of-function mutations. Although SHANK3 haploinsufficiency has been associated with the major neurological symptoms of PMS, it cannot explain the clinical variability seen among individuals. Our goals were to characterize a Brazilian cohort of PMS individuals, explore the genotype-phenotype correlation underlying this syndrome, and describe an atypical individual with mild phenotype. Methodology: A total of 34 PMS individuals were clinically and genetically evaluated. Data were obtained by a questionnaire answered by parents, and dysmorphic features were assessed via photographic evaluation. We analyzed 22q13.3 deletions and other potentially pathogenic copy number variants (CNVs) and also performed genotype-phenotype correlation analysis to determine whether comorbidities, speech status, and ASD correlate to deletion size. Finally, a Brazilian cohort of 829 ASD individuals and another independent cohort of 2297 ID individuals was used to determine the frequency of PMS in these disorders. Results: Our data showed that 21% (6/29) of the PMS individuals presented an additional rare CNV, which may contribute to clinical variability in PMS. -
Klinefelter, Turner & Down Syndrome
Klinefelter, Turner & Down Syndrome A brief discussion of gamete forma2on, Mitosis and Meiosis: h7ps://www.youtube.com/watch?v=zGVBAHAsjJM Non-disjunction in Meiosis: • Nondisjunction "not coming apart" is the failure of a chromosome pair to separate properly during meiosis 1, or of two chromatids of a chromosome to separate properly during meiosis 2 or mitosis. • Can effect each pair. • Not a rare event. • As a result, one daughter cell has two chromosomes or two chromatids and the other has none • The result of this error is ANEUPLOIDY. 4 haploid gametes 2 gametes with diploid 2 gametes with haploid number of x and 2 lacking number of X chromosome, 1 x chromosome gamete with diploid number of X chromosome, and 1 gamete lacking X chromosome MEIOSIS MITOSIS Nondisjunc2on at meiosis 1 = All gametes will be abnormal Nondisjunc2on at meiosis 2 = Half of the gametes are normal (%50 normal and %50 abnormal) Down’s Syndrome • Karyotype: 47, XY, +21 Three copies of chromosome 21 (21 trisomy) • The incidence of trisomy 21 rises sharply with increasing maternal age (above 37), but Down syndrome can also be the result of nondisjunction of the father's chromosome 21 (%15 of cases) • A small proportion of cases is mosaic* and probably arise from a non-disjunction event in early zygotic division. *“Mosaicism, used to describe the presence of more than one type of cells in a person. For example, when a baby is born with Down syndrome, the doctor will take a blood sample to perform a chromosome study. Typically, 20 different cells are analyzed. -
A Randomized Controlled Trial of Intranasal Oxytocin in Phelan-Mcdermid Syndrome
A Randomized Controlled Trial of Intranasal Oxytocin in Phelan-McDermid Syndrome Jarrett Fastman Icahn School of Medicine at Mount Sinai Jennifer Foss-Feig Icahn School of Medicine at Mount Sinai Yitzchak Frank Icahn School of Medicine at Mount Sinai Danielle Halpern Icahn School of Medicine at Mount Sinai Hala Harony-Nicolas Icahn School of Medicine at Mount Sinai Christina Layton Icahn School of Medicine at Mount Sinai Sven Sandin Icahn School of Medicine at Mount Sinai Paige Siper Icahn School of Medicine at Mount Sinai Lara Tang Icahn School of Medicine at Mount Sinai Pilar Trelles Icahn School of Medicine at Mount Sinai Jessica Zweifach Icahn School of Medicine at Mount Sinai Joseph D. Buxbaum Icahn School of Medicine at Mount Sinai Alexander Kolevzon ( [email protected] ) Icahn School of Medicine at Mount Sinai https://orcid.org/0000-0001-8129-2671 Research Article Keywords: Phelan-McDermid syndrome, PMS, shank3, autism spectrum disorder, ASD, oxytocin Posted Date: March 5th, 2021 Page 1/24 DOI: https://doi.org/10.21203/rs.3.rs-268151/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 2/24 Abstract Background Phelan-McDermid syndrome (PMS) is a rare neurodevelopmental disorder caused by haploinsuciency of the SHANK3 gene and characterized by global developmental delays, decits in speech and motor function, and autism spectrum disorder (ASD). Monogenic causes of ASD such as PMS are well suited to investigations with novel therapeutics, as interventions can be targeted based on established genetic etiology. While preclinical studies have demonstrated that the neuropeptide oxytocin can reverse electrophysiological, attentional, and social recognition memory decits in Shank3-decient rats, there have been no trials in individuals with PMS. -
22Q13.3 Deletion Syndrome
22q13.3 deletion syndrome Description 22q13.3 deletion syndrome, which is also known as Phelan-McDermid syndrome, is a disorder caused by the loss of a small piece of chromosome 22. The deletion occurs near the end of the chromosome at a location designated q13.3. The features of 22q13.3 deletion syndrome vary widely and involve many parts of the body. Characteristic signs and symptoms include developmental delay, moderate to profound intellectual disability, decreased muscle tone (hypotonia), and absent or delayed speech. Some people with this condition have autism or autistic-like behavior that affects communication and social interaction, such as poor eye contact, sensitivity to touch, and aggressive behaviors. They may also chew on non-food items such as clothing. Less frequently, people with this condition have seizures or lose skills they had already acquired (developmental regression). Individuals with 22q13.3 deletion syndrome tend to have a decreased sensitivity to pain. Many also have a reduced ability to sweat, which can lead to a greater risk of overheating and dehydration. Some people with this condition have episodes of frequent vomiting and nausea (cyclic vomiting) and backflow of stomach acids into the esophagus (gastroesophageal reflux). People with 22q13.3 deletion syndrome typically have distinctive facial features, including a long, narrow head; prominent ears; a pointed chin; droopy eyelids (ptosis); and deep-set eyes. Other physical features seen with this condition include large and fleshy hands and/or feet, a fusion of the second and third toes (syndactyly), and small or abnormal toenails. Some affected individuals have rapid (accelerated) growth. -
Dr. Fern Tsien, Dept. of Genetics, LSUHSC, NO, LA Down Syndrome
COMMON TYPES OF CHROMOSOME ABNORMALITIES Dr. Fern Tsien, Dept. of Genetics, LSUHSC, NO, LA A. Trisomy: instead of having the normal two copies of each chromosome, an individual has three of a particular chromosome. Which chromosome is trisomic determines the type and severity of the disorder. Down syndrome or Trisomy 21, is the most common trisomy, occurring in 1 per 800 births (about 3,400) a year in the United States. It is one of the most common genetic birth defects. According to the National Down Syndrome Society, there are more than 400,000 individuals with Down syndrome in the United States. Patients with Down syndrome have three copies of their 21 chromosomes instead of the normal two. The major clinical features of Down syndrome patients include low muscle tone, small stature, an upward slant to the eyes, a single deep crease across the center of the palm, mental retardation, and physical abnormalities, including heart and intestinal defects, and increased risk of leukemia. Every person with Down syndrome is a unique individual and may possess these characteristics to different degrees. Down syndrome patients Karyotype of a male patient with trisomy 21 What are the causes of Down syndrome? • 95% of all Down syndrome patients have a trisomy due to nondisjunction before fertilization • 1-2% have a mosaic karyotype due to nondisjunction after fertilization • 3-4% are due to a translocation 1. Nondisjunction refers to the failure of chromosomes to separate during cell division in the formation of the egg, sperm, or the fetus, causing an abnormal number of chromosomes. As a result, the baby may have an extra chromosome (trisomy). -
Rare Double Aneuploidy in Down Syndrome (Down- Klinefelter Syndrome)
Research Article Journal of Molecular and Genetic Volume 14:2, 2020 DOI: 10.37421/jmgm.2020.14.444 Medicine ISSN: 1747-0862 Open Access Rare Double Aneuploidy in Down Syndrome (Down- Klinefelter Syndrome) Al-Buali Majed J1*, Al-Nahwi Fawatim A2, Al-Nowaiser Naziha A2, Al-Ali Rhaya A2, Al-Khamis Abdullah H2 and Al-Bahrani Hassan M2 1Deputy Chairman of Medical Genetic Unite, Pediatrics Department, Maternity Children Hospital Al-hassa, Hofuf, Saudi Arabia 2Pediatrics Resident, Pediatrics Department, Maternity Children Hospital Alhassa, Hofuf, Saudi Arabia Abstract Background: The chromosomal aneuploidy described as Cytogenetic condition characterized by abnormality in numbers of the chromosome. Aneuploid patient either trisomy or monosomy, can occur in both sex chromosomes as well as autosome chromosomes. However, double aneuploidies involving both sex and autosome chromosomes relatively a rare phenomenon. In present study, we reported a double aneuploidy (Down-Klinefelter syndrome) in infant from Saudi Arabia. Materials and Methods: In the present investigation, chromosomal analysis (standard chromosomal karyotyping) and fluorescence in situ hybridization (FISH) were performed according to the standard protocols. Results: Here, we report a single affected individual (boy) having Saudi origin, suffering from double chromosomal aneuploidy. The main presenting complaint is the obvious dysmorphic features suggesting Down syndrome. Chromosomal analysis and FISH revealed 48,XXY,+21, show the presence of three copies of chromosome 21, two copies of X chromosome and one copy of Y chromosome chromosomes. Conclusion: Patients with Down syndrome must be tested for other associated sex chromosome aneuploidies. Hence, proper diagnosis is needed for proper management and the cytogenetic tests should be performed as the first diagnostic approach. -
Down-Syndrome.Pdf
Down syndrome Description Down syndrome is a chromosomal condition that is associated with intellectual disability, a characteristic facial appearance, and weak muscle tone (hypotonia) in infancy. All affected individuals experience cognitive delays, but the intellectual disability is usually mild to moderate. People with Down syndrome often have a characteristic facial appearance that includes a flattened appearance to the face, outside corners of the eyes that point upward ( upslanting palpebral fissures), small ears, a short neck, and a tongue that tends to stick out of the mouth. Affected individuals may have a variety of birth defects. Many people with Down syndrome have small hands and feet and a single crease across the palms of the hands. About half of all affected children are born with a heart defect. Digestive abnormalities, such as a blockage of the intestine, are less common. Individuals with Down syndrome have an increased risk of developing several medical conditions. These include gastroesophageal reflux, which is a backflow of acidic stomach contents into the esophagus, and celiac disease, which is an intolerance of a wheat protein called gluten. About 15 percent of people with Down syndrome have an underactive thyroid gland (hypothyroidism). The thyroid gland is a butterfly-shaped organ in the lower neck that produces hormones. Individuals with Down syndrome also have an increased risk of hearing and vision problems. Additionally, a small percentage of children with Down syndrome develop cancer of blood-forming cells (leukemia). Delayed development and behavioral problems are often reported in children with Down syndrome. Affected individuals can have growth problems and their speech and language develop later and more slowly than in children without Down syndrome. -
Three-Dimensional Fluorescence in Situ Hybridization in Mouse
Three-Dimensional Fluorescence In Situ Hybridization in Mouse Embryos Using Repetitive Probe Sequences Walid Maalouf, Tiphaine Aguirre-Lavin, Laetitia Herzog, Isabelle Bataillon, Pascale Debey, Nathalie Beaujean To cite this version: Walid Maalouf, Tiphaine Aguirre-Lavin, Laetitia Herzog, Isabelle Bataillon, Pascale Debey, et al.. Three-Dimensional Fluorescence In Situ Hybridization in Mouse Embryos Using Repetitive Probe Sequences. Fluorescence in situ Hybridization (FISH), 659 (4), Springer, pp.401-408, 2010, Methods in Molecular Biology, 10.1007/978-1-60761-789-1_31. hal-02610638 HAL Id: hal-02610638 https://hal.archives-ouvertes.fr/hal-02610638 Submitted on 17 May 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. 1 Three-Dimensional Fluorescent In Situ Hybridisation in Mouse Embryos Walid E. Maalouf1,2, Tiphaine Aguirre-Lavin1, Laetitia Herzog1, Isabelle Bataillon1, Pascale Debey1 and Nathalie Beaujean1 1INRA, UMR 1198 Biologie du Développement et Reproduction, F-78350 Jouy en Josas, France 32 Present Address: QMRI, 47 Little France Crescent, University of Edinburgh, Edinburgh, UK Contact : Dr Walid Maalouf <[email protected]>, Tel. +33 (0)1 34 65 29 03 / Fax: 29 09 Abstract A common problem in research laboratories that study the mammalian embryo is the limited supply of live material. -
Double Aneuploidy in Down Syndrome
Chapter 6 Double Aneuploidy in Down Syndrome Fatma Soylemez Additional information is available at the end of the chapter http://dx.doi.org/10.5772/60438 Abstract Aneuploidy is the second most important category of chromosome mutations relat‐ ing to abnormal chromosome number. It generally arises by nondisjunction at ei‐ ther the first or second meiotic division. However, the existence of two chromosomal abnormalities involving both autosomal and sex chromosomes in the same individual is relatively a rare phenomenon. The underlying mechanism in‐ volved in the formation of double aneuploidy is not well understood. Parental ori‐ gin is studied only in a small number of cases and both nondisjunctions occurring in a single parent is an extremely rare event. This chapter reviews the characteristics of double aneuploidies in Down syndrome have been discussed in the light of the published reports. Keywords: Double aneuploidy, Down Syndrome, Klinefelter Syndrome, Chromo‐ some abnormalities 1. Introduction With the discovery in 1956 that the correct chromosome number in humans is 46, the new area of clinical cytogenetic began its rapid growth. Several major chromosomal syndromes with altered numbers of chromosomes were reported, such as Down syndrome (trisomy 21), Turner syndrome (45,X) and Klinefelter syndrome (47,XXY). Since then it has been well established that chromosome abnormalities contribute significantly to genetic disease resulting in reproductive loss, infertility, stillbirths, congenital anomalies, abnormal sexual development, mental retardation and pathogenesis of malignancy [1]. Clinical features of patients with common autosomal or sex chromosome aneuploidy is shown in Table 1. © 2015 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. -
Your Baby and Down Syndrome
• • I thought my pregnancy was What will the future hold for my normal. What happened? baby with Down syndrome? About 80% of children with Down People with Down syndrome have some level of Welcoming syndrome are born to mothers under intellectual disability, which can be anywhere your son or age 35. Mothers over 35 have a from mild to severe. Most are somewhere in daughter into higher chance of having a between. No one can look at any infant and the world will baby with Down syndrome. know how intelligent, successful or independent bring joy to you It’s not certain how or why he or she will be in the future. and your family. this happens. Without Your baby will be just specific medical tests, it like other babies in most is impossible to tell if an Today, people with Down unborn child might have ways. He or she will play, enjoy life and like syndrome are achieving more Down syndrome. to learn new things. Like any parent, you with advances in health care and may have some questions about your baby. increased opportunities in education. With support, many can: This brochure is a starting point for learning • move out of the family home about Down syndrome, resources and • take care of themselves support groups. • hold regular jobs • participate in leisure activities congratulations • live rich and full lives answers How might Down syndrome to questions you might have affect my baby’s health? Babies with Down syndrome might be affected What is Down syndrome? What if I want to have another baby? by any of the following health conditions: There are about 350,000 people in the United If you are planning to have more children, ask your • difficulty breastfeeding States with Down syndrome, the most common doctor about your chances for having another child • low muscle tone genetic disorder. -
Advances in Autism Genetics: on the Threshold of a New Neurobiology
REVIEWS Advances in autism genetics: on the threshold of a new neurobiology Brett S. Abrahams and Daniel H. Geschwind Abstract | Autism is a heterogeneous syndrome defined by impairments in three core domains: social interaction, language and range of interests. Recent work has led to the identification of several autism susceptibility genes and an increased appreciation of the contribution of de novo and inherited copy number variation. Promising strategies are also being applied to identify common genetic risk variants. Systems biology approaches, including array-based expression profiling, are poised to provide additional insights into this group of disorders, in which heterogeneity, both genetic and phenotypic, is emerging as a dominant theme. Gene association studies Autistic disorder is the most severe end of a group of into the ASDs. This work, in concert with important A set of methods that is used neurodevelopmental disorders referred to as autism technical advances, made it possible to carry out the to determine the correlation spectrum disorders (ASDs), all of which share the com- first candidate gene association studies and resequenc- (positive or negative) between mon feature of dysfunctional reciprocal social interac- ing efforts in the late 1990s. Whole-genome linkage a defined genetic variant and a studies phenotype of interest. tion. A meta-analysis of ASD prevalence rates suggests followed, and were used to identify additional that approximately 37 in 10,000 individuals are affected1. loci of potential interest. Although -
Aggression, Rage and Dyscontrol in Neurological Diseases of Children
Journal of Pediatric Neurology 2003; 1(1): 9-14 www.jpneurology.org REVIEW ARTICLE Aggression, rage and dyscontrol in neurological diseases of children Jayaprakash A. Gosalakkal University Hospitals of Leicester, Leicestershire and Warwick Medical School, Leicester, U.K. Abstract that aggression has a neuroanatomic and chemical basis, that developmental and acquired brain Behavioral neurology has been bridging disorders contribute to recurrent interpersonal the gap between neurology and psychiatry in violence, that both biologic and sociologic factors children. There are several neuropsychiatric are involved, and that to ignore either is to invite disorders of children in which aggression is a error (2). dominant symptom. Both global disorders like There are several neuropsychiatric disorders attention deficit hyperactivity disorder as well of children in which aggression is a dominant as localized dysfunction of the brain may lead symptom e.g. Lesch-Nyhan syndrome, Prader-Willi to aggression. A number of neurometabolic syndrome etc (Tables 1 and 2). Self-mutilation has disorders as well as post-epileptic and post- been seen in 15% of institutionalized mentally surgical states may present with aggression retarded patients (3). Physical and verbal aggression in children. Drugs are sometimes effective may also be a symptom of frontal lobe epilepsy in especially in combination with a multimode children in association with other psychological approach. In this review some of the more deficits (4). Rage outbursts and increased aggression common causes for aggression in neurologically have been noted to occur in higher rates in children impaired children, the associated co-morbidities with temporal lobe epilepsy (5). and treatment are discussed. (J Pediatr Neurol Aggression can be seen both in previously 2003; 1(1): 9-14).