Birth Defects

What is mosaicism?

The ability to find normal alleles within a mutated person due to recombination. So in a male with XXY disorder, you can find normal XY sperm in his testicles and even though he is sterile due to his condition, these sperm can be injected a normal oocyte and he can father a child this way.

What are the factors associated with increased incidence of Birth Defects?

Parental age Season of the year Country of residence Race Familial tendencies

As a physician, how would you explain the following to a young couple expecting their first child and who are having concerns that something may go wrong? -Factors which are associated with increased incidence of anomalies? There are 5 of them.

Parental age - advanced maternal age is a risk for Down Syndrome. Advanced paternal age is a risk for Apert's syndrome and achondroplasia. Season of the year - in Ireland, there is increased anencephaly in infants born in the Spring. Country of residence of parents - Celtic populations have higher risks of anencephaly. Could be linked with thalidomide. Race - cleft plate is 2x more common in Caucasians than African Americans. Familial tendencies - Polydactyly is more common in the Amish population.

How would you explain the following to a couple having a child with one of them? Sequence?

Pattern or cascade of secondary anomalies stemming from a SINGLE PRIMARY anomaly or initiating factor. I.e. Potter's - a bunch of facial deformities due to the reduction of amniotic fluid during pregnancy.

How would you explain the following to a couple having a child with one of them? Field effect?

Polytophic Field Effect - a pattern of anomalies affecting a single developmental field. I.e. a whole organ or portion of the body missing.

How would you explain the following to a couple having a child with one of them? Normal morphological variation of a particular sequence?

Predictable variants of the average morphological pattern that are usually not (but can be) clinically significant. Very common. Use this term with patients above others due to sensitivity.

Match the timing of the following developmental disorder with the following periods: Defects? A) Embryonic Period B) Embryonic Period and for some of the Fetal Period C) Embryonic to Fetal Period D) Late in Fetal Period

A

How would you explain the following to a couple having a child with one of them? Association?

A NONRANDOM occurrence of events that take place with NO KNOWN CAUSE by CHANCE alone. Thus, the changes occur in groups.

How would you explain the following to a couple having a child with one of them? Defects where terms ending in -plasia or -trophy are used as modifiers?

-plasia = related to cell division -trophy - related to cell growth

What are the chances of having a major birth defect given the # of minor defects found in a baby? 1 2 3 >3

1 -> 1% (cue to look for major defects) 2 -> 3% 3 -> 10% >3 -> 90%

The incidence of children who have a clinically significant birth defect.

2-3% of all children born in the US.

The incidence of birth defects that cause infant mortality.

20%

How would you explain the following to a couple having a child with one of them? Deformation?

A deformation is an abnormal form, shape, or position caused by nondisruptive mechanical forces. They can be reversed or corrected after birth.

How would you explain the following to a couple having a child with one of them? Syndrome?

A group of primary anomalies that are seen together and are related by a common cause. Thus, the cause MUST be known. I.e. FAS - fetal alcohol syndrome- there are well recognized deformities and abnormalities associated with FAS and the COMMON CAUSE is alcohol ingestion during pregnancy amongst other biological factors.

What are teratogens?

Any agent that can produce or increase the incidence of an anomaly between fertilization and birth. They must also produce morphological anomalies and be extrinsic to the embryo. They are most effective during the Sensitive or Critical period of development = Weeks 3-8. Remember, the benefits of treatment for the mother MUST be weighed against the risks of the developing embryo/fetus.

Match the timing of the following developmental disorder with the following choices: Dysplasias? A) Embryonic Period B) Embryonic Period and for some of the Fetal Period C) Embryonic to Fetal Period D) Late in Fetal Period

B

As a physician, how would you explain the following to a young couple expecting their first child and who are having concerns that something may go wrong? - The nature of birth defects? -Congenital Anomalies? -Congenital Malformations?

Birth defects, congenital anomalies, and congenital malformations (defects) are all used interchangeably to describe the consequences of abnormal development. A birth defect is any defect present at birth regardless of whether it was detected at the time of birth.

Match the timing of the following developmental disorder with the following choices: Disruptions? A) Embryonic Period B) Embryonic Period and for some of the Fetal Period C) Embryonic to Fetal Period D) Late in Fetal Period

C

Match the timing of the following developmental disorder with the following choices: Deformations? A) Embryonic Period B) Embryonic Period and for some of the Fetal Period C) Embryonic to Fetal Period D) Late in Fetal Period

D

How would you explain the following to a couple having a child with one of them? Dysplasia?

Disorders that affect tissue structure and organization. Cell shape or size altered.

How would you explain the following to a couple having a child with one of them? Disruption? / Multifactorial effect?

Disruption is a breakdown of a normal development or process causing a malformation. They are extrinsic and not inherited. Examples are vascular accidents or amniotic bands. When an inherited defect causes an influence on a disruption, then it is a multifactorial effect.

How would you explain the following to a couple having a child with one of them? Dominant / recessive / sex-linked inheritance?

Dominant - when a mutation is expressed in the phenotype Recessive - when a mutation is transferred but not expressed (carrier) unless dominant recessive. Sex-linked - when a mutation is tied to either X or Y chromosome inheritance. Truly only Y because it is the only TRUE sex chromosome but there are X-linked disorders.

What are the major trisomies?

Edwards -Trisomy 18 Pau - Trisomy 13 Down - Trisomy 21

How would you explain the following to a couple having a child with one of them? Defect?

Malformations caused by abnormal development mechanisms and processes. They are intrinsic and inheritable. They manifest as partial organs or altered formation of organs/body regions.

What are the major categories or classes of environmental agents which cause abnormal development? Give significant examples of each type of agent.

Maternal infections Ionizing radiation / Physical agents Drugs / chemicals Hypoxia Heavy Metals Imbalance of essential metabolites or hormones - hyper or hypo production. Maternal factors - diabetes, uterine anomalies, smoking Paternal factors - chemical agents, radiation, advanced age.

As a physician, how would you explain the following to a young couple expecting their first child and who are having concerns that something may go wrong? -The incidence of major and minor anomalies?

Minor Defects - have no significant medical or social burden and are found in 14% of children. Major Defects - more common in Early Embryos and if the defect occurs in the first two weeks of embryonic development, then it often leads to a spontaneous abortion. The incidence of major defects can be predicted by calculation from the number of known minor defects in the fetus.

As a physician, how would you explain the following to a young couple expecting their first child and who are having concerns that something may go wrong? -The major causes of birth defects?

Unknown!

What is the major cause of Aneuploidy?

When the chromosome number is NOT an exact multiple of the haploid number. Lethal

What is polyploidy?

When the chromosome number is an EXACT multiple of the haploid number that is GREATER than 2. Lethal

What is the only human monosomic condition known to be compatible with life?

X in an XX person because typically one of the two X's is inactivated anyway. But if it was XY then this would be lethal if the X was not present because a person cannot exist as just a Y.