UNSW Embryology

Abnormal Development

© Dr Mark Hill (2008)

Acknowledgements

Introduction

These notes cover abnormalities that can occur during development often described as congenital defects. There are many different ways that developmental abnormalities can occur the 2 major types are Genetic (inherited) and Environmental (maternal) derived abnormalities.

Human Chromosomes	Young child with smallpox scars (Image CDC)

While genetic abnormalites will have well-defined impacts upon development, maternally derived effects can be harder to define and variable depending on many different factors (for example: time, exposure, and combination with other factors).

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. In addition, these two major causes can also interact giving a broad spectrum of both major and minor abnormalities. This section of notes also includes, twinning and statistical information relating to abnormalities at birth from several different countries.

Page Links: Introduction | Some Recent Findings | Genetic Abnormalities | Environmental Abnormalities | Abnormalities by System | Statistics | Finally | Glossary

Some Recent Findings

Sharkey FH, Maher E, FitzPatrick DR.   [See Related Articles] Chromosome analysis: what and when to request. Arch Dis Child. 2005 Dec;90(12):1264-9. Review.

"Chromosome abnormalities have long been recognised as an important cause of learning disability and multiple malformation syndromes; 0.8% of live born infants have numerical or structural chromosomal anomalies resulting in an abnormal phenotype."

Lammer EJ, Shaw GM, Iovannisci DM, Finnell RH.    [See Related Articles] Maternal smoking, genetic variation of glutathione s-transferases, and risk for orofacial clefts. Epidemiology. 2005 Sep;16(5):698-701.

Malone FD, Canick JA, Ball RH, Nyberg DA, Comstock CH, Bukowski R, Berkowitz RL, Gross SJ, Dugoff L, Craigo SD, Timor-Tritsch IE, Carr SR, Wolfe HM, Dukes K, Bianchi DW, Rudnicka AR, Hackshaw AK, Lambert-Messerlian G, Wald NJ, D'Alton ME    [See Related Articles] First- and Second-Trimester Evaluation of Risk (FASTER) Research Consortium. First-trimester or second-trimester screening, or both, for Down's syndrome. N Engl J Med. 2005 Nov 10;353(19):2001-11.

"First-trimester combined screening at 11 weeks of gestation is better than second-trimester quadruple screening but at 13 weeks has results similar to second-trimester quadruple screening.

Genetic Abnormalities

Embryos with major genetic abnormalities, that impact on developmental processes, in general fail to develop and are spontaneously aborted. In other embryos, there are several known genetic abnormalities (on the basis of maternal age or family history) that can now be screened for with prenatal testing. (More? Genetic Abnormalities).

In terms of maternal/paternal family history, some ethnic backgrounds have been shown to have disease-associated genetic variants, though most common genetic diseases are consistent across ethnic boundaries. For example: Caucasians of northern European ancestry and cystic fibrosis (CTFR gene), Mediterranean, Asian and Far Eastern ancestry with beta-thalassaemia. (More? Genetic Abnormalities)

Many genetic developmental abnormalities involve only small DNA mutations affecting individual or a few genes, exceptions to this are those that involve abnormal segregation of chromosomes giving an abnormal chromosome complement to the developing embryo.

The most common trisomy (the number indicates the affected chromosome) is Down syndrome (or trisomy 21) and then Edwards syndrome (trisomy 18, there is also less commonly trisomy 9, 13, 15). Note that the occurance of chromosomal abnormalities also increases with increasing maternal age.

There are many pamphlets providing information about prenatal diagnosis (see NSW State Health Publication Checking your baby's health before birth).

Environmental Abnormalities

Environmental abnormalities (often called maternal derived) relate to lifestyle, infection, maternal health and nutrition. The following list of topics is in no specific order and links to more detailed pages. (More? Maternal Abnormalities)

Infections, collectively grouped under the acronym TORCH for Toxoplasmosis, Other organisms (parvovirus, HIV, Epstein-Barr, herpes 6 and 8, varicella, syphilis, enterovirus) , Rubella, Cytomegalovirus and Hepatitis. See also a page on bacterial infections and viral infections.

Infections (as well as other environmental conditions) can also lead to increases in maternal core body temperature, Maternal Hyperthermia, which has also been shown in animal models to be a potent teratogen.

Maternal drugs effects either alcohol (fetal alcohol syndrome), smoking, prescription drugs (therapeutic chemicals/agents, thalidomide limb development), non-prescription drugs (smoking, herbal), and illegal drugs (Cannabis/Marijuana, Methamphetamine/Amphetamine, Cocaine, Heroin, Lysergic Acid Diethylamide)

Environment, for example smoking, chemical, heavy metals. Other maternal maternal effects include changes in endocrine function (maternal diabetes, thyroid development).

In addition to these obvious environmentally derived abnormalities, there is growing evidence that the interuterine environment has a strong influence on later postnatal health and neurological development. This theory is based on the early statistical analysis of disease/longevity in babies with low birth weights in England by Barker, and was initially called the "Barker Hypothesis" and now called the Fetal Origins Hypothesis.

(More? Environmental)

Abnormalities by Week

The links below take you to the developmental abnormalities associated with the first 3 weeks of development. Additional pages relating to specific abnormalities will be linked from these introductory pages.

Week 1 | Week 2 | Week 3

Abnormalities by System

The links below take you to the related systems abnormality page in each section of Notes. Additional pages relating to specific abnormalities will also be linked from these introductory pages.

Neural Development | Heart / Cardiovascular | Musculoskeletal | Musculoskeletal - Limb | Gastrointestinal Tract | Head and Neck | Coelomic cavity Respiratory | Neural Crest | Senses - General Eye, Ear, Nose | Senses - Ear | Senses - Eye | Urogenital | Genital | Endocrine | Endocrine - Adrenal | Integumentary

Statistics

A better understanding of abnormal development can also be gained from looking at normal birth statistics. Statistics on prenatal diagnosis, birth and prenatal/postnatal development (growth, neural development) not only give us normal values for the population, but also identify health trends and potential genetic/environmental influences on development.

This site contains several resources for statistical data and Australian statistical data that has been derived from the Australian Institute of Health and Welfare National Perinatal Statistics Unit, UNSW (More? NPSU) which publishes "Congenital Malformations Australia" every 2 years. Be aware that some congenital abnormalities, by their nature, affect multiple systems.

In the USA, the Center for Disease Control (CDC) keeps and publishes relevant statistical information.

Finally

While in general many twins develop normally, the process of twinning is an abnormality that is covered in this section of notes.

Also note that each section of the notes covering normal early development and specific systems (top lefthand menu) contain references to specific abnormalities (on Page 2 of each notes section, see quick links below).

Abnormal Development - Other Pages: Autism | Fragile X

Where to Next?

To understand the impact of abnormal development, you need to understand normal development. Development Notes 1 Development Notes 2

Alternatively, go on to look at Systematic Development of organs and tissues.

Glossary of Terms

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

Quick Links

The quick link below is to Page 2 (abnormal development) of each system.

System Notes ----------------- Heart/Cardiovascular Respiratory Coelomic cavity Gastrointestinal Tract Head and Neck Neural Neural Crest Eye Ear Nose Endocrine Urogenital Musculoskeletal Integumentary

The quick links below are to the earlier stages of development.

Development Notes ----------------- Menstrual Cycle Week 1 Week 2 Week 3 Week 4 Placenta Serial Images Genes/DNA Molecular Dev Abnormal Dev Postnatal Dev Notes Index

Finally

For those wanting to see dynamic processes of development (and have a reasonably quick connection) then the Movies pages are good for watching changes occur.

Movies ----------------- Embryo Growth Carnegie Stages Ultrasound Images Stage 13/14 Embryo Stage 22 Embryo Heart Septation Neural Neural Crest Other Embryos Larsen Movies

Other Embryos

The study of human development has relied extensively on studying the process in other model animals. For those wanting to see the process of development in other species then the other embryos pages are a good start.

Other Embryos ----------------- Chicken Fly Frog Mouse Rabbit Rat Worm Zebrafish Guinea Pig

UNSW Embryology ISBN: 978 0 7334 2609 4

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