Human Abnormal Development

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Contents

Introduction

How and why do things go wrong in development?

Mother with child, face and body showing smallpox scars.

These notes cover abnormalities that can occur during development often described as congenital defects or birth defects. There are many different ways that developmental abnormalities can occur the 3 major types are Genetic (inherited), Environmental (maternal) and Unknown (not determined) derived abnormalities. The environmental factors that cause or lead to any of these abnormalities are described as Teratogens.

Note that genetic an environmental effects can also interact and it is this and the group now classified as "unknown causes" that require further research to place them in one of the two other real categories.


Please note that abnormal development pages may contain clinical images not suitable for children.


Abnormality Links: Introduction | Genetic | Environmental | Unknown | Teratogens | Cardiovascular | Coelomic Cavity | Endocrine | Gastrointestinal Tract | Genital | Head | Integumentary | Musculoskeletal | Limb | Neural | Neural Crest | Renal | Respiratory | Placenta | Sensory | Twinning | Developmental Origins of Health and Disease | ICD-10

Prenatal Diagnosis

Prenatal diagnosis are the clinical tools used to determine both normal and abnormal development. There are a growing number of new diagnostic techniques that are being applied to human embryonic development. Tests that occur after birth are described in Neonatal Diagnosis.

Diagnosis Links: Prenatal Diagnosis | Pregnancy Test | Amniocentesis | Chorionic villus sampling | Ultrasound | Alpha-Fetoprotein | Pregnancy-associated plasma protein-A | Fetal Blood Sampling | Magnetic Resonance Imaging | Computed Tomography | Preimplantation Genetic Screening | Comparative Genomic Hybridization | Genome Sequencing | Neonatal Diagnosis | Category:Prenatal Diagnosis | Fetal Surgery | Classification of Diseases | Category:Neonatal Diagnosis | 2013 BGD Tutorial - Applied Embryology and Teratology

Genetic

Genetic Links: Introduction | Genetic risk maternal age | Trisomy 21 | Trisomy 18 | Trisomy X | Fragile X | Williams | Philadelphia chromosome | Prenatal Diagnosis | Neonatal Diagnosis | International Classification of Diseases | Molecular Development - Genetics | Cell Division - Meiosis | Cell Division - Mitosis

Environmental

While genetic abnormalities will have well-defined impacts upon development, environmentally derived effects can be harder to define and often variable depending on many different factors (timing, exposure level, and the combination effects with other factors). This combination effect can also be seen between genetic and environmental interacting to give an even broader spectrum of both major and minor abnormalities.

Environmental Links: Introduction | Low Folic Acid | Iodine Deficiency | Nutrition | Drugs | Australian Drug Categories | USA Drug Categories | Thalidomide | Herbal Drugs | Illegal Drugs | Smoking | Fetal Alcohol Syndrome | TORCH Infections | Viral Infection | Bacterial Infection | Zoonotic Infection | Toxoplasmosis | Malaria | Iodine Deficiency | Maternal Diabetes | Maternal Hyperthermia | Maternal Inflammation | Biological Toxins | Chemicals | Heavy Metals | Radiation | Prenatal Diagnosis | Neonatal Diagnosis | International Classification of Diseases | Fetal Origins Hypothesis


Often not considered, is that pregnancy itself can also expose abnormalities in the mother (congenital heart disease, diabetes, reproductive disorders) that until then had gone undetected. This section of notes also includes links to prenatal diagnosis techniques, twinning and statistical information relating to abnormalities at birth from several different countries.

Undergraduate Science Projects

The links below are to Science student group projects prepared on the topics of prenatal diagnosis (2010) and abnormal development (2011).


2011 Student Projects: Turner Syndrome | DiGeorge Syndrome | Klinefelter's Syndrome | Huntington's Disease | Fragile X Syndrome | Tetralogy of Fallot | Angelman Syndrome | Friedreich's Ataxia | Williams-Beuren Syndrome | Duchenne Muscular Dystrolphy | Cleft Palate and Lip


2010 Student Projects: Ultrasound | Chorionic villus sampling | Amniocentesis | Percutaneous Umbilical Cord Blood Sampling | Fetal Fibronectin | Maternal serum alpha-fetoprotein

Statistics

Australia - Top 10

Australian Data 1981-92

The ten most frequently reported birth defects in Victoria between 2003-2004.

  1. Hypospadias
  2. Obstructive Defects of the Renal Pelvis or Obstructive Genitourinary Defects
  3. Ventricular Septal Defect
  4. Congenital Dislocated Hip
  5. Trisomy 21 or Down syndrome
  6. Hydrocephalus
  7. Cleft Palate
  8. Trisomy 18 or Edward Syndrome - multiple abnormalities of the heart, diaphragm, lungs, kidneys, ureters and palate 86% discontinued.
  9. Renal Agenesis/Dysgenesis - reduction in neonatal death and stillbirth since 1993 may be due to the more severe cases being identified in utero and being represented amongst the increased proportion of terminations (approximately 31%).
  10. Cleft Lip and Palate - occur with another defect in 33.7% of cases.


Links: ACAMS | Australian Statistics

USA - Selected


Links: USA Monitoring Programmes | USA Statistics

Neural Tube Defects

Neural tube defects that were just outside the top ten most common birth defects but are widely known.

Spina Bifida - (73%) of parents choose to discontinue a pregnancy affected by spina bifida.
Anencephaly - (94%) of parents choose to discontinue a pregnancy affected by anencephaly.
Data: from the Victorian Perinatal Data Collection Unit

Links: Folic Acid | Neural System - Abnormalities

Genetic (inherited)

Genetic Links: Introduction | Genetic risk maternal age | Trisomy 21 | Trisomy 18 | Trisomy X | Fragile X | Williams | Philadelphia chromosome | Prenatal Diagnosis | Neonatal Diagnosis | International Classification of Diseases | Molecular Development - Genetics


Environmental (maternal)

Environmental Links: Introduction | Low Folic Acid | Iodine Deficiency | Nutrition | Drugs | Australian Drug Categories | USA Drug Categories | Thalidomide | Herbal Drugs | Illegal Drugs | Smoking | Fetal Alcohol Syndrome | TORCH Infections | Viral Infection | Bacterial Infection | Zoonotic Infection | Toxoplasmosis | Malaria | Iodine Deficiency | Maternal Diabetes | Maternal Hyperthermia | Maternal Inflammation | Biological Toxins | Chemicals | Heavy Metals | Radiation | Prenatal Diagnosis | Neonatal Diagnosis | International Classification of Diseases | Fetal Origins Hypothesis


Critical Periods

The table below identifies approximate windows of time, "critical periods", that following exposure to teratogens can lead to developmental abnormalities (anomalies, congenital). In general, the effects for each system are more severe (major anomalies) in the embryonic period during organogenesis in the first trimester. Later teratogen exposure are less severe (minor anomalies) in the fetal period during continued growth and differentiation in the second and third trimester.

Conceptus Embryonic development (weeks) Fetal period (weeks)
1
2
3
4
5
6
7
8
9
16
20-36
38
Early zygote.jpg Week2 001 icon.jpg Stage9 sem4c.jpg Stage13 sem1c.jpg Stage15 bf1c.jpg Stage17 bf1c.jpg Stage19 bf1c.jpg Stage23 bf1c.jpg
Neural
Stage2.jpg Heart
Upper limbs
Lower limbs
Ear
Eye
CSt3.jpg Palate
Teeth
Week2 001 icon.jpg External genitalia
Loss Major abnormalities Functional and Minor abnormalities

Teratology

Now consider how different environmental effects during pregnancy may influence developmental outcomes. The terms listed below are often used to describe these environmental effects

  • Teratogen (Greek, teraton = monster) any agent that causes a structural abnormality (congenital abnormalities) following fetal exposure during pregnancy. The overall effect depends on dosage and time of exposure. (More? Critical Periods of Development)
  • Absolute risk the rate of occurrence of an abnormal phenotype among individuals exposed to the agent. (e.g. fetal alcohol syndrome)
  • Relative risk the ratio of the rate of the condition among the exposed and the nonexposed. (e.g. smokers risk of having a low birth weight baby compared to non-smokers) A high relative risk may indicate a low absolute risk if the condition is rare.
  • Mutagen a chemical or agent that can cause permanent damage to the deoxyribonucleic acid (DNA) in a cell. DNA damage in the human egg or sperm may lead to reduced fertility, spontaneous abortion (miscarriage), birth defects and heritable diseases.
  • Fetotoxicant is a chemical that adversely affects the developing fetus, resulting in low birth weight, symptoms of poisoning at birth or stillbirth (fetus dies before it is born).
  • Synergism when the combined effect of exposure to more than one chemical at one time, or to a chemical in combination with other hazards (heat, radiation, infection) results in effects of such exposure to be greater than the sum of the individual effects of each hazard by itself.
  • Toxicogenomics the interaction between the genome, chemicals in the environment, and disease. Cells exposed to a stress, drug or toxicant respond by altering the pattern of expression of genes within their chromosomes. Based on new genetic and microarray technologies.


Australian Congenital Anomalies Monitoring System

The following text is from AIHW National Perinatal Epidemiology and Statistics Unit Australian Congenital Anomalies Monitoring System (ACAMS)

"The Australian Congenital Anomalies Monitoring System (ACAMS) contains data based on notifications of major congenital anomalies to birth defects registers in New South Wales, Victoria, Western Australia and South Australia and on data collected on congenital anomalies in Queensland, Tasmania and the Australian Capital Territory. The Northern Territory is currently unable to provide data in a format enabling it to be compiled with data from the other states and territories. Some summary data have been provided by the Northern Territory for inclusion in the ACAS. Congenital anomalies are mainly notified from data collected as part of perinatal collections. Other sources of data include perinatal death certificates, cytogenetic or pathology reports, admitted patient data, maternal and child health nurses and medical officers.
Information is included on live births and stillbirths of 20 weeks gestational age or more or 400 grams birthweight or more (including induced abortions) with a congenital anomaly for all states and the Australian Capital Territory. Information on induced abortions of less than 20 weeks gestational age and less than 400 grams weight with a congenital anomaly is only available for four states and is included for: New South Wales, Victoria, Western Australia and South Australia. Births included in the ACAS are also included in the National Perinatal Data Collection.
The period of notification varies among the state and territory collections and ranges from prenatal diagnosis to notification up to 15 years of age. For New South Wales, the data include births with congenital anomalies notified up to 1 year of age. The data for Victoria, Western Australia and South Australia include births with congenital anomalies notified up to 15 years, 6 years and 5 years of age respectively. The data for Queensland, Tasmania, and the Australia Capital Territory include births with congenital anomalies notified in the perinatal period.
Data items relating to the woman, including demographic characteristics and factors relating to the birth, and data items relating to the baby, including, birthweight, gestational age and sex, are included. Congenital anomalies are coded using the British Paediatric Association Classification of Diseases (ICD-9-BPA), which is based on the International Classification of Diseases, 9th Revision (ICD-9).
ACAS supersedes the National Congenital Malformations and Birth Defects Data Collection (NCM&BD), which commenced in 1981 in response to claims of increased incidence of congenital anomalies in small areas of Australia. Data were provided by four jurisdictions in 1998–1985 and all states and territories provided data from 1986. Data are included up to and including the 1997 birth cohort. The NCM&BD data collection was reviewed in 2004 and the development of the ACAS was a recommendation of the review."


Links: Australian Congenital Anomalies Monitoring System (ACAMS) | Australian Institute of Health and Welfare (AIHW)

New Zealand

New Zealand Birth Defects Monitoring Programme (NZBDMP)

  • monitoring the occurrence of birth defects among livebirths and fetal deaths in New Zealand.
  • provide data on the prevalence of birth defects for ad hoc.
  • provide annual data to the Ministry of Health and International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR)
  • investigate clusters of birth defects
  • provide expert technical assistance and advice on the epidemiology of birth defects

USA Monitoring Programmes

Centers for Disease Control (CDC) conducted two birth defects surveillance systems[1] and each state also maintain their own programs (see External Links).

  • Metropolitan Atlanta Congenital Defects Programme (MACDP)
  • Birth Defects Monitoring Programme (BDMP)
    • a nationwide surveillance system that monitors 1 million births per year.


USA Selected - CDC National estimates for 21 selected major birth defects (2004–2006).

Birth Defects Cases per Births (1 in ...) Estimated Annual Number of Cases
Anencephaly 4,859 859
Spina bifida without anencephaly 2,858 1,460
Encephalocele 12,235 341
Anophthalmia/microphthalmia 5,349 780
Common truncus 13,876 301
Transposition of great arteries 3,333 1,252
Tetralogy of Fallot 2,518 1,657
Atrioventricular septal defect 2,122 1,966
Hypoplastic left heart syndrome 4,344 960
Cleft palate without cleft lip 1,574 2,651
Cleft lip with and without cleft palate 940 4,437
Esophageal atresia/tracheoesophageal fistula 4,608 905
Rectal and large intestinal atresia/stenosis 2,138 1,952
Reduction deformity, upper limbs 2,869 1,454
Reduction deformity, lower limbs 5,949 701
Gastroschisis 2,229 1,871
Omphalocele 5,386 775
Diaphragmatic hernia 3,836 1,088
Trisomy 13 7,906 528
Trisomy 21 (Down syndrome) 691 6,037
Trisomy 18 3,762 1,109
Links: Human Abnormal Development | CDC Birth Defects - Data & Statistics

International Classification of Diseases

The International Classification of Diseases (ICD) is the standard diagnostic tool for epidemiology, health management and clinical purposes. This includes the analysis of the general health situation of population groups. It is used to monitor the incidence and prevalence of diseases and other health problems.

International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) Version for 2010

Chapter XVII Congenital malformations, deformations and chromosomal abnormalities (Q00-Q99) Excl.: inborn errors of metabolism (E70-E90)

  • Congenital malformations of the nervous system.
  • Congenital malformations of eye, ear, face and neck.
  • Congenital malformations of the circulatory system.
  • Congenital malformations of the respiratory system.
  • Cleft lip and cleft palate.
  • Other congenital malformations of the digestive system.
  • Congenital malformations of genital organs.
  • Congenital malformations of the urinary system.
  • Congenital malformations and deformations of the musculoskeletal system.
  • Other congenital malformations.
  • Chromosomal abnormalities, not elsewhere classified.


Links: International Classification of Diseases

Terms

  • abnormal - term describing development that is different from normal or not typical, usual, or regular.
  • association - term referring to a nonrandom occurrence in two or more individuals of multiple defects not known to be a polytopic field defect, sequence, or syndrome.
  • Australian Congenital Anomalies Monitoring System - (ACAMS) contains data based on notifications of major congenital anomalies to birth defects registers in Australian states and territories, except the Northern Territory. Information is included on live births and stillbirths of 20 weeks gestational age or more or 400 grams birthweight or more (including induced abortions) with a congenital anomaly. ACAMS replaces the National Congenital Malformations and Birth Defects Data Collection that began in 1981. (More? Australian Statistics | AIHW National Perinatal Epidemiology and Statistics Unit)
  • congenital - (Latin, congenitus = born together) refers to developmental disorder that is present at birth (or during the neonatal period) due to genetic, environmental or a combination of known and unknown factors.
  • dysmorphology - term referring to the study of birth defects.
  • environmental - term used to describe effects due to the physical and biological factors resulting in abnormal development.
  • genetic - term used to describe effects due to embryo genes, their mutation, altered expression or epigenetic effects resulting in abnormal development.
  • International Classification of Diseases - (ICD) is the standard diagnostic tool for epidemiology, health management and clinical purposes. This classification has been developed by the World Health Organization (WHO). ICD-10 came into use in 1994, ICD-11 revision has begun and will continue until 2015. (More? International Classification of Diseases | WHO - ICD)
  • polytopic field defect - term describing developmental defects that are all concentrated in one particular area of the body (developmental field).
  • sequence - clinical term for a pattern of multiple defects derived from a single known or presumed structural defect or mechanical factor.
  • syndrome - clinical term for a pattern of multiple defects related pathogenetically though not known to represent a single sequence or a polytopic field defect.
  • unknown - term used to describe abnormal development due to single or multiple genetic and or environmental effects that have not yet been completely identified or described.

External Links

External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name.


Glossary Links

A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols


Cite this page: Hill, M.A. (2014) Embryology Human Abnormal Development. Retrieved April 18, 2014, from http://embryology.med.unsw.edu.au/embryology/index.php?title=Human_Abnormal_Development

What Links Here?
Dr Mark Hill 2014, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G
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