Glostrup. Most developmental disabilities begin before a baby is born, but some can happen after birth because of injury, infection, or other factors. In addition to the disorders with known genetic cause that are associated with intellectual disability, autism and ADHD, an increasing number of novel recurrent structural variants are identified in association with these developmental disorders. Thalidomide, which is an inhibitor of tumor necrosis factor-α, is still a drug of choice in the treatment of leprosy and multiple myeloma. Another is amelia, in which a limb is entirely missing. Purpose of review: Developmental disorders, including intellectual disability, autism and attention deficit hyperactivity disorder (ADHD), are neuropsychiatric disorders that manifest in early childhood as deviations from the normal development. Numerical errors of chromosomes result in aneuploidy, defined as a total number of chromosomes other than the normal 46. Epub 2020 Apr 1. Fiksinski AM, Schneider M, Murphy CM, Armando M, Vicari S, Canyelles JM, Gothelf D, Eliez S, Breetvelt EJ, Arango C, Vorstman JAS. Some of the common classes of malformations are listed in Table 8.1. A classic example of the last is the incidence of severely malformed infants as a result of exposure to thalidomide. The factors underlying developmental disorders are complex. Some influences cause anomalies if the embryo is exposed to them early in development, but they are innocuous at later periods of pregnancy. Fjorden Hospital. One example is phocomelia (which means “seal limb”), a condition in which the hands and feet seem to arise almost directly from the shoulder and hip (Fig. Glostrup Hospital. Despite much effort, however, the causes of most congenital malformations are still unknown. According to most studies, approximately 2% to 3% of all living newborns show at least one recognizable congenital malformation. 8.8). Lin BD, Colas F, Nijman IJ, Medic J, Brands W, Parr JR, van Eijk KR, Klauck SM, Chiocchetti AG, Freitag CM, Maestrini E, Bacchelli E, Coon H, Vicente A, Oliveira G, Pagnamenta AT, Gallagher L, Ennis S, Anney R, Bourgeron T, Luykx JJ, Vorstman J. Transl Psychiatry. A good example is the increased occurrence of extra digits among some families within the Amish community in the United States. Anomalies arising from the third to the ninth month of pregnancy tend to be functional (e.g., mental retardation) or involve disturbances in the growth of already formed body parts. This fetus had not been exposed to thalidomide. This continuum includes defects that constitute abnormal structure, function, metabolism, and behavior. The incidence of cleft palate among whites is twice as high as it is among blacks and twice as high among Korean, Chinese, and Japanese persons as among whites. Am J Med Genet B Neuropsychiatr Genet. Cleft lip and cleft palate are common. Periods and degrees of susceptibility of embryonic organs to teratogens. Each person has many thousands of genetic variations that can interact to influence how the brain develops. When seen in humans or animals, malformations were often interpreted as omens of good or evil. The most narrow concept is used in the category Specific Disorders of Psychological Development in the ICD-10. The opinions expressed are those of the authors and do not necessarily represent the views of the Editor or IACAPAP. Developmental and behavioral disorders are often treated as chronic health conditions. One possibility is that a single teratogen acted on the primordia of several organs during susceptible periods of development. Noting that learning disabilities and developmental disorders are more prevalent in boys than girls, Dr Jaclyn Schwarz and her team at the Department of Psychological and Brain Sciences, University of Delaware are investigating the underlying causes. October 2005; Trends in Cognitive Sciences 9(10) :465-466; DOI: 10.1016/j.tics.2005.08.003. About 20 years later, the effects of thalidomide sensitized the medical community to the potential danger of certain drugs and other environmental teratogens (agents that produce birth defects) to the developing embryo. Scientists call this polygenic riskbecause it’s the combined effect of many genes. Al-Mubarak BR, Omar A, Baz B, Al-Abdulaziz B, Magrashi AI, Al-Yemni E, Jabaan A, Monies D, Abouelhoda M, Abebe D, Ghaziuddin M, Al-Tassan NA. The primary disorders are Autism/Autistic Disorder, Asperger's Syndrome and Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS). Am J Med Genet A. We've made it easy to understand developmental disorders with this user-friendly and engaging chapter. Eur J Hum Genet. Although medical embryology textbooks traditionally cover principally structural defects—congenital malformations—there is a continuum between purely biochemical abnormalities and defects that are manifested as abnormal structures. If parents have enough of these DNA changes affecting parts of the brain that are important for language, the child may have DLD. Epub 2018 Sep 8. Some individuals with monosomy of the sex chromosomes (45XO genotype) can survive, however (Fig. DEVELOPMENTAL DISORDERS Chapter C.1 Xiaoyan Ke & Jing Liu INTELLECTUAL DISABILITY This publication is intended for professionals training or practicing in mental health and not for the general public. 2015 Mar;56(3):251-73. doi: 10.1111/jcpp.12374. Well-known correlations exist between parental age and the incidence of certain malformations. Another is that a genetic or chromosomal defect spanned genes affecting a variety of structures, or that a single metabolic defect affected different developing structures in different ways. Pervasive developmental disorders (PDDs) are a set of behavioral disorders that are present since early childhood. Because thalidomide was not approved by the Food and Drug Administration, the United States was spared from this epidemic of birth defects. One example is. 8.3). J Child Psychol Psychiatry. The high incidence of this anomaly in pregnancies beginning in the early spring may relate to nutritional deficiencies of mothers during the late winter months. Despite considerable research since the 1960s, the cause of at least 50% of human congenital malformations remains unknown (Fig. Psychopathology. Despite the high number of causative or contributing genes, functional studies of these genes indicate a large degree of convergence into a smaller number of neurobiological pathways. Annual research review: impact of advances in genetics in understanding developmental psychopathology. Another classic example of the influence of country as a factor in the incidence of malformations is seen in neural tube defects (Table 8.2). Among the factors associated with increased incidences of congenital malformations are (1) parental age, (2) season of the year, (3) country of residence, (4) race, and (5) familial tendencies. Causes and Risk Factors. In light of the recognition of the importance of folic acid in the prevention of neural tube defects, it is possible that the high incidence of anencephaly in Ireland resulted from poor nutrition in pregnant women during the winter. Prevalence and architecture of de novo mutations in developmental disorders. Am J Med Genet B Neuropsychiatr Genet. The present incidence in Ireland is much decreased. NIH At certain critical periods during pregnancy, embryos are more susceptible to agents or factors causing abnormal development than at other times. As far back as the classical Greek period, people speculated that maternal impressions during pregnancy (e.g., being frightened by an animal) caused development to go awry. ; RICH (B.) A classic correlation is the increased incidence of Down syndrome (Fig. Click to share on Twitter (Opens in new window), Click to share on Facebook (Opens in new window), Click to share on Google+ (Opens in new window), Presurgical Functional MappingAndrew C. Papanicolaou, Roozbeh Rezaie, Shalini Narayana, Marina Kilintari, Asim F. Choudhri, Frederick A. Boop, and James W. Wheless, the Child With SeizureDon K. Mathew and Lawrence D. Morton, and Pharmacologic Consequences of SeizuresShilpa D. Kadam and Michael V. Johnston, Self-Limited EpilepsiesDouglas R. Nordli, Jr., Colin D. Ferrie, and Chrysostomos P. Panayiotopoulos, in Epilepsy: A Network and Neurodevelopmental PerspectiveRaman Sankar and Edward C. Cooper, Hematology, Oncology and Palliative Medicine, Early representations of some malformed infants are remarkable in their anatomical accuracy, and it is often possible to diagnose specific conditions or syndromes from the ancient art (, In the early nineteenth century, Etienne Geoffroy de St. Hilaire coined the term, The first of two major milestones in human teratology occurred in 1941, when Gregg in Australia recognized that the, Thalidomide is a very effective sedative that was widely used in West Germany, Australia, and other countries during the late 1950s. Studies on mice have shown that defective function of many genes leads to some sort of developmental disturbance. In the case of genetically based malformations or anomalies based on chromosomal aberrations, the defect is intrinsic and is commonly expressed even in a normal environment. Anencephaly (Fig. Soon, physicians began to see infants born with extremely rare birth defects. Major causes of congenital malformations. Costain G, Walker S, Argiropoulos B, Baribeau DA, Bassett AS, Boot E, Devriendt K, Kellam B, Marshall CR, Prasad A, Serrano MA, Stavropoulos DJ, Twede H, Vermeesch JR, Vorstman JAS, Scherer SW. J Neurodev Disord. Before the critical period, exposure to a known teratogen has little influence on development.  |  Because thalidomide was not approved by the Food and Drug Administration, the United States was spared from this epidemic of birth defects. Source AUTISM, Vol 3, N° 1, 1999, pages 7-16, réf. NLM Bispebjerg Hospital. Recognizing that the primary factors leading to anencephaly occur during the first month of embryonic life, researchers must seek the potential environmental causes that are more prevalent in April. The relationship between the country of residence and an increased incidence of specific malformations can be related to various factors, including racial tendencies, local environmental factors, and even governmental policies. Race is a factor in many congenital malformations and a variety of diseases. Certain other influences (e.g., intrauterine diseases, toxins) may result in the destruction of all or parts of structures that have already been formed. Genetically based malformations can be caused by abnormalities of chromosomal division or by mutations of genes. So, just as a single change in the bases of your DNA code can cause rare developmental disorders, so too can transposons,” says Gardner. The period of maximal susceptibility to abnormal development occurs between weeks 3 and 8, which is the period when most of the major organs and body regions are first being established. 8.7). 8.6). Pathogenic variants in over 1,000 genes are already known to cause diverse developmental disorders (DDs) as a result of perturbed embryonic and fetal development, and yet the high prevalence of undiagnosed patients suggests that many more genetic causes … The role of rare compound heterozygous events in autism spectrum disorder. Monosomy (the lack of one member of a chromosome pair) and trisomy (a triplet instead of the normal chromosome pair) are typically the result of nondisjunction during meiosis (see Fig. Some of the possible causes of Developmental Disorders or similar disorders may include: Absence of septum pellucidum (learning disabilities) Adrenoleukodystrophy (learning disabilities) Adult ADHD (developmental disorder) Aicardi Syndrome (developmental abnormalities) Alcohol Abuse (developmental disorders) Andersen-Tawil syndrome (developmental abnormalities) Anemia … Developmental disabilities begin anytime during the developmental period and usually last throughout a person’s lifetime. In other cases, environment and genetics interact. By the Middle Ages, however, representations of malformations were much more imaginative, with hybrids of humans and other animals often represented (Fig. Typically, a developing organ has a curve of susceptibility to teratogenic influences similar to that illustrated in Figure 8.5. J Child Psychol Psychiatry. Recent findings: Neurodevelopmental disorders are neurologically based conditions that can interfere with the acquisition, retention, or application of specific skills or sets of information. Congenital malformations have attracted attention since the dawn of human history. Plotting the causes of developmental disorders. A greater than threefold decrease in the incidence of neural tube defects in Ireland from 1980 to 1994 may be related to both better nutrition and folic acid supplementation by a certain percentage of pregnant women. Such a simplified view of susceptible periods does not take into account, however, the possibility that a teratogen or some other harmful influence may be applied at an early stage of development, but not be expressed as a developmental disturbance until later during embryogenesis. Summary: Among the factors associated with increased incidences of congenital, Well-known correlations exist between parental age and the incidence of certain malformations. The prevalence and incidence of developmental stuttering vary significantly per year according to country and region. These cases were concentrated in West Germany and Australia because the drug was commonly sold in these locations. With the intense investigations that followed the thalidomide disaster, modern teratology came of age. At present, in the majority of cases a cause cannot be found.  |  However, in the past 5 years major advances have been made in the identification of specific genetic … Individuals with Down syndrome are typically mentally retarded and have a characteristic broad face with a flat nasal bridge, wide-set eyes, and prominent epicanthic folds. Research into the causes of developmental disorders has identified 285 genes linked to these conditions, including 28 newly-associated genes. The results of many investigations have allowed the following generalization: Insults to the embryo during the first 3 weeks of embryogenesis (the early period before organogenesis begins) are unlikely to result in defective development because they either kill the embryo or are compensated for by the powerful regulatory properties of the early embryo. Many of the disease risk variants display incomplete penetrance, indicating that additional genetic, and possibly nongenetic, factors are relevant. Not all teratogenic influences act in the same developmental periods (, Despite considerable research since the 1960s, the cause of at least 50% of human congenital malformations remains unknown (. In other cultures, women who gave birth to malformed infants were assumed to have had dealings with the devil or other evil spirits. Some of these defects are purely mutational, residing in the structure of the DNA itself, whereas others result from interference in transcription or translation or from regulatory elements of the gene. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. Whole exome sequencing in ADHD trios from single and multi-incident families implicates new candidate genes and highlights polygenic transmission. Organs that form the earliest (e.g., heart) tend to be sensitive to the effects of teratogens earlier than organs that form later (e.g., external genitalia). Roughly 18% of malformations can be attributed to genetic causes (chromosomal defects or mutations based on mendelian genetics), and 7% of malformations are caused by environmental factors, such as physical or chemical teratogens. A classic example of the last is the incidence of severely malformed infants as a result of exposure to thalidomide. Some types of anomalies have a higher incidence among infants born at certain seasons of the year. Generalized susceptibility curve to teratogenic influences by a single organ. After the flowering of experimental embryology and genetics in the early twentieth century, laboratory researchers began to produce specific recognizable congenital anomalies by means of defined experimental genetic or laboratory manipulations on laboratory animals. Loss of SMPD4 Causes a Developmental Disorder Characterized by Microcephaly and Congenital Arthrogryposis Sphingomyelinases generate ceramide from sphingomyelin as a second messenger in intracellular signaling pathways involved in cell proliferation, differentiation, or apoptosis. Table 8.4 summarizes some of the various types of deletions and duplications of the sex chromosomes. Causes of pervasive developmental disorder. A good example is the increased occurrence of extra digits among some families within the Amish community in the United States. Learning disabilities are diagnosed when the children are young and just beginning school. At present, they are understood more at the level of statistical associations than as points of interference with specific developmental controls, but they are important clues to why development can go wrong. 8.2). Extensive studies in the past 30 years have established that cyclin-dependent kinases (CDKs) exert many diverse, important functions in a number of molecular and cellular processes that are at play during development. Many of these causes are likely to result from some environmental factor influencing the expression of a developmentally critical gene. The best known is trisomy 21, also called Down syndrome. Thalidomide is a very effective sedative that was widely used in West Germany, Australia, and other countries during the late 1950s. malformations are (1) parental age, (2) season of the year, (3) country of residence, (4) race, and (5) familial tendencies. The basic information is encoded in the genes, but as the genetic instructions unfold, the developing structures or organs are subjected to microenvironmental or macroenvironmental influences that either are compatible with or interfere with normal development. Faily S, Perveen R, Urquhart J, Chandler K, Clayton-Smith J. 8.1B). Some of the common classes of malformations are listed in, Several factors are associated with various types of congenital malformations. Developmental stuttering is the most common form of stuttering. Congenital defects range from enzyme deficiencies caused by single nucleotide substitutions in the DNA molecule to very complex associations of gross anatomical abnormalities. In most cases, polyploid embryos abort spontaneously early in pregnancy. (Data from Persaud TVN, Chudley AE, Skalko RG, eds: Abnormal numbers of the sex chromosomes are relatively common and can be detected by examination of the sex chromatin (X chromosome) or the fluorescence reactions of the Y chromosomes.