Congenital Defects, Genetic and Chromosomal Disorders

Flashcards about congenital defects, genetic and chromosomal disorders

What are Congenital Defects?

Abnormalities of body structure, function, or metabolism present at birth, affecting over 185,000 infants in the US annually and are the leading cause of infant death.

What are the causes of Congenital Defects?

Genetic factors (single-gene, multifactorial inheritance, chromosomal aberrations) or environmental factors during embryonic or fetal development (maternal disease, infections, drugs).

What causes most Genetic Disorders?

Changes in the DNA sequence that alter the synthesis of a single-gene product, chromosomal aberrations, or abnormal chromosome number.

What is a Phenotype?

The observable expression of a genotype in terms of physical or biochemical traits.

What is a Gene Mutation?

A biochemical event, such as nucleotide changes, deletion, or insertion, that produces a new allele for a particular gene.

What are Single-Gene Disorders?

Caused by a defective or mutant allele at a single-gene locus and follow Mendelian patterns of inheritance; transmission patterns are autosomal dominant, autosomal recessive, or X-linked.

How do Single-Gene Disorders manifest?

Virtually all single-gene disorders lead to the formation of an abnormal protein or the decreased production of a gene product, resulting in systemic alterations.

Significance of Huntington Chorea

Neurodegenerative disorder

Significance of Marfan Syndrome

Connective tissue disorder with abnormalities in the skeletal, ocular, cardiovascular systems

Significance of Von Willebrand disease

Bleeding Disorder

Significance of Cystic Fibrosis

Disorder of membrane transport of chloride ions in exocrine glands causing lung and pancreatic disease

Significance of Oculocutaneous Albinism

Hypopigmentation of skin, hair, eyes as a result of inability to synthesize melanin

Significance of Sickle Cell Disease

Red blood cell defect

Significance of Fragile X syndrome

Intellectual disability

What are Autosomal Dominant Disorders?

A single mutant allele from an affected parent is transmitted to offspring regardless of sex; affected parent has a 50% chance of transmitting the disorder.

What is Reduced Penetrance?

When a person inherits a dominant mutant allele but fails to exhibit the associated phenotype.

What is Variable Expressivity?

Autosomal dominant disorders can display variable expressivity, meaning they can be expressed differently in people that carry the mutant gene.

What is Marfan Syndrome?

An autosomal dominant disorder of the connective tissue affecting fibrillin I, coded by the FBNI gene on chromosome 15q21, with a prevalence of 1 per 5,000.

What characterizes Type 1 Neurofibromatosis (NF1)?

Cutaneous and subcutaneous neurofibromas, pigmented nodules of the iris (Lisch nodules), and large, flat cutaneous pigmentations known as café au lait spots.

What characterizes Type 2 Neurofibromatosis (NF2)?

Characterized by tumors of the acoustic nerve, often asymptomatic for the first 15 years of life, with symptoms including headaches, hearing loss, and tinnitus.

What are Autosomal Recessive Disorders?

Both alleles of the gene pair are affected (homozygous); both parents are unaffected carriers. Each pregnancy has risks of one in four for an affected child, two in four for a carrier child, and one in four for a normal child.

What causes autosomal recessive disorders?

Characteristically caused by loss-of-function mutations that impair or eliminate the function of an enzyme.

What is Phenylketonuria (PKU)?

Deficiency of the liver enzyme phenylalanine hydroxylase, leading to toxic levels of phenylalanine in tissues and blood.

What is Tay-Sachs Disease?

A variant of lysosomal storage diseases (gangliosidoses) where there is a failure to break down GM2 gangliosides of cell membranes.

What are X-Linked Recessive Disorders?

Almost always associated with the X chromosome and predominantly recessive. Females (XX) are carriers, while males (XY) are typically affected, with a 50% chance of transmission from carrier mother to sons.

What are some examples of X-Linked Recessive Disorders?

Include color blindness, glucose-6-phosphate dehydrogenase deficiency, hemophilia A, and X-linked agammaglobulinemia.

What characterizes X-Linked Dominant Disorders?

The disease will affect both males and females that inherit a copy of the mutated X chromosome. Affected females transmit the disorder to 50% of offspring regardless of sex; affected males have 100% affected daughters and 100% normal sons.

What is Fragile X Syndrome?

A single-gene disorder causing intellectual disability, characterized by amplification of a CGG repeat at Xq27 on the fragile site, FXTR1.

In autosomal recessive disorders, when is the phenotype seen?

The phenotype is only seen in the homozygous recessive genotype.

What are Multifactorial Disorders?

Multiple genes along with environmental factors; don't follow single-gene inheritance patterns. Risk of recurrence in future pregnancies is high for the same or a similar defect.

What is Cleft Lip and Cleft Palate?

Developmentally originates around the 35th day of gestation when the frontal prominences fuse with the maxillary process; may be caused by teratogens or chromosomal abnormalities.

How do chromosomes replicate in human cells?

During mitosis, somatic cells receive 46 chromosomes in 23 pairs, but germ cells undergoing meiosis receive 23 individual chromosomes.

How do structural chromosomal abnormalities occur?

They result from breakage in one or more chromosomes during meiosis, followed by rearrangement or deletion of chromosome parts, caused by radiation, chemicals, or viral infections.

What is Monosomy?

The presence of only one member of a chromosome pair; severe defects that often cause miscarriage.

What is Polysomy?

More than two chromosomes to a set; Trisomy 21 (Down syndrome) being the most common.

What is Down Syndrome (Trisomy 21)?

Caused by nondisjunction during meiosis, resulting in a trisomy of chromosome 21; risk increases with maternal age.

What is Turner Syndrome?

An absence of all (45, X/0) or part of the X chromosome, affecting 1 in 2,500 live births in females; characterized by short stature and loss of oocytes before birth.

What is Klinefelter Syndrome?

Testicular dysgenesis accompanied by one or more extra X chromosomes (47, XXY) due to nondisjunction during meiotic division; phenotypic changes include enlarged breasts, sparse facial hair, and small testes.

How are Mitochondrial Gene Disorders inherited?

Passed from the biological mother to all her children due to mutations in mitochondrial DNA (mtDNA); clinical expression depends on the content of mitochondrial genes and the proportion that is mutant.

How do environmental factors influence the fetus?

Maternal smoking is associated with lower than normal neonatal weight, maternal use of alcohol is known to cause fetal abnormalities, various drugs can cause early miscarriage, infectious agents cause congenital malformations, and radiation can cause chromosomal and genetic defects.

What is the period of organogenesis?

The time when differentiation and development of organs take place, extending from day 15 to day 60 after conception.

What is a Teratogenic Agent?

A chemical, physical, or biologic agent that produces abnormalities during embryonic or fetal development.

What are some examples of Environmental Chemicals and Drugs that are teratogenic?

Organic mercurials, drugs used in cancer treatment, warfarin, anticonvulsant drugs, ethyl alcohol, and cocaine.

What is fetal alcohol syndrome, and why does it occur?

Leads to physical, behavioral and cognitive fetal abnormalities due to alcohol consumption during pregnancy. The concentrations of alcohol in the fetus are at least as high as in the biological mother.

What infectious agents are frequently implicated in fetal anomalies?

Agents frequently implicated in fetal anomalies: toxoplasmosis, other, rubella, cytomegalovirus, and herpes.

What are effects of Folic Acid Deficiency?

Birth defects related to exposure to a teratogenic agent, deficiencies of nutrients and vitamins also may be a factor. Leads to the development of neural tube defects (NTDs) (e.g., anencephaly, spina bifida, encephalocele).

What are the goals of genetic assessment and counseling?

To determine whether the defect was inherited and the risk of recurrence. Prenatal diagnosis provides a means of determining whether an unborn child has certain types of abnormalities.

What does genetic counseling involve?

Help the family to understand the problem and can support educated decisions about whether or not to have more children.

What are some methods used for prenatal diagnosis?

Ultrasonography, maternal serum (blood) screening tests, amniocentesis, chorionic villus sampling, and percutaneous umbilical fetal blood sampling

What is AFP (Alpha-Fetoprotein)?

AFP is a major fetal plasma protein and has a structure similar to the albumin found in postnatal life. Fetal plasma levels of AFP peak at approximately 10 to 13 weeks’ gestation and decrease until the third trimester when the level peaks again.

What is the genetic component in geriatric considerations for Parkinson disease and Alzheimer disease?

Genetic component mutations in certain genes Parkinson disease and Alzheimer disease.