3.4: Genetic and Chromosomal Abnormalities

Before we explore development, let's begin with a consideration of the abnormalities that can be present within the directions for development - conditions that arise from the presence of a specific gene or genes and conditions that are due to differences at the level of the chromosome. Genetic conditions are those caused by the expression of a gene. We can describe genetic conditions based on how they are inherited or their inheritance patterns. Because genetic conditions involve a specific gene or genes, their effects are more specific, more isolated. In contrast, chromosomal conditions are those that involve an entire chromosome or a large chunk of chromosome.

Genetic Inheritance Patterns

Genes reside on chromosomes and, ultimately, provide the directions for making proteins that direct development. Genetic conditions - and genetic traits more generally - exhibit three different types of inheritance patterns.

Recessive

Recessive conditions are caused by a gene that is typically only expressed if the gene is received from both parents. In other words, you'd have to inherit the gene from both parents in order for the trait to be evident in your phenotype. 

• "Recessive is a quality found in the relationship between two versions of a gene. Individuals receive one version of a gene, called an allele, from each parent. If the alleles are different, the dominant allele will be expressed, while the effect of the other allele, called recessive, is masked. In the case of a recessive genetic disorder, an individual must inherit two copies of the mutated allele in order for the disease to be present." (from the National Human Genome Research Institute)
• As you may suspect, recessive traits and conditions are less commonly expressed as they must be received from both parents in order to impact the phenotype. And the expression of such things increases when members of a species are closely related.
• Examples of recessive disorders - sickle cell, Tay-Sachs, cystic fibrosis.

Dominant

Dominant conditions are those that require only one gene for you to express them. In other words, if you inherit the gene, you inherit the condition. As noted previously, Huntington's Disease in an example of a dominant condition.

• "Autosomal dominance is a pattern of inheritance characteristic of some genetic diseases. "Autosomal" means that the gene in question is located on one of the numbered, or non-sex, chromosomes. 'Dominant' means that a single copy of the disease-associated mutation is enough to cause the disease. This is in contrast to a recessive disorder, where two copies of the mutation are needed to cause the disease. Huntington's disease is a common example of an autosomal dominant genetic disorder." (from the National Human Genome Research Institute)

Sex-linked Genetic

These are, again, conditions caused by a gene - but they are unique in that the gene resides on one of the 23rd chromosomes - the X or the Y. Most sex-linked genetic conditions are on the X chromosome, so we refer to them as "X-linked". Hemophilia is one example of an X-linked recessive condition. This means it is preferentially seen in males as the gene for the condition resides on the X chromosome and genetic males don't have a 2nd X chromosome that could carry the dominant non-hemophilia gene to over-ride the recessive gene for hemophilia.

• "Sex linked is a trait in which a gene is located on a sex chromosome. In humans, the term generally refers to traits that are influenced by genes on the X chromosome. This is because the X chromosome is large and contains many more genes than the smaller Y chromosome. In a sex-linked disease, it is usually males who are affected because they have a single copy of X chromosome that carries the mutation. In females, the effect of the mutation may be masked by the second healthy copy of the X chromosome." (from the National Human Genome Research Institute)
• The most common form of "color-blindness" is a sex-linked genetic condition - X-linked and recessive. Consequently, it is rare for a female to be color-blind.

Chromosomal Disorders

Conditions can be causes by a gene or a select group of genes - and they can be a consequence of missing genes. We also have conditions that are due to an error at the level of the whole chromosome - which means many genes are involved. And we have conditions that involve a loss of some part of a chromosome. As the nature of conditions that are due to some element of a chromosome being impacted is very diverse, we're going to focus on conditions that involve the whole chromosome. And here we will make two distinctions - those that involve the twenty-two non-sex chromosomes and those that involve the 23rd chromosomes, X or Y. We'll focus on three conditions as a means of introducing these sorts of disorders, Down syndrome, Turner syndrome, and Klinefelter syndrome. Tyler and Edman (2004), offer this overview:

Down syndrome, Turner syndrome, and Klinefelter syndrome constitute the most common chromosomal abnormalities encountered by primary care physicians. Down syndrome typically is recognized at birth, Turner syndrome often is not recognized until adolescence, and many men with Klinefelter syndrome are never diagnosed. Although each syndrome is caused by an abnormal number of chromosomes, or aneuploidy, they are distinct syndromes with learning disabilities and a predisposition toward autoimmune diseases, endocrinologic disorders, and cancers. Optimal health care requires a thorough knowledge of the unique health risks, psychoeducational needs, functional capabilities, and phenotypic variation associated with each condition.

All three conditions share one common feature - an abnormal chromosomal number.

Autosomal (Non-sex) Chromosomal Disorders

Down syndrome, trisomy 21, is a relatively common chromosomal disorder. Individuals with this condition have three copies (trisomy) of the 21st chromosome. "Autosomal" chromosomal disorders involve abnormal numbers of the non-sex chromosomes, chromosomes 1-22. The following information about Down syndrome consists of excerpts from a National Institutes of Health (NIH) website.

Down syndrome is a chromosomal condition that is associated with intellectual disability, a characteristic facial appearance, and weak muscle tone (hypotonia) in infancy. All affected individuals experience cognitive delays, but the intellectual disability is usually mild to moderate.

People with Down syndrome often have a characteristic facial appearance that includes a flattened appearance to the face, outside corners of the eyes that point upward (Elements of Morphology, National Human Genome Research InstituteUse of illustrations and other content" data-remote="/art/large/upslanting-palpebral-fissures.jpeg" data-source-href="https://elementsofmorphology.nih.gov...03f00fcb26b7c4" data-title="Upslanting palpebral fissures" data-toggle="lightbox" href="https://ghr.nlm.nih.gov/art/large/up...-fissures.jpeg" target="_blank" title="Image">upslanting palpebral fissures), small ears, Credit: Elements of Morphology, National Human Genome Research InstituteUse of illustrations and other content" data-remote="/art/large/short-neck.jpeg" data-source-href="https://elementsofmorphology.nih.gov/index.cgi?tid=c75e63fd749ec7a8" data-title="Short neck" data-toggle="lightbox" href="https://ghr.nlm.nih.gov/art/large/short-neck.jpeg" target="_blank" title="Image">a short neck, and a tongue that tends to stick out of the mouth. Affected individuals may have a variety of birth defects. Many people with Down syndrome have small hands and feet and Use of illustrations and other content" data-remote="/art/large/single-transverse-palmar-crease.jpeg" data-title="Single transverse palmar crease" data-toggle="lightbox" href="https://ghr.nlm.nih.gov/art/large/single-transverse-palmar-crease.jpeg" target="_blank" title="Image">a single crease across the palms of the hands. About half of all affected children are born with a heart defect. Digestive abnormalities, such as a blockage of the intestine, are less common.

Down syndrome occurs in about 1 in 700 newborns. About 5,300 babies with Down syndrome are born in the United States each year, and approximately 200,000 people in this country have the condition. Although women of any age can have a child with Down syndrome, the chance of having a child with this condition increases as a woman gets older.

Most cases of Down syndrome result from Use of illustrations and other content" data-remote="/art/large/trisomy.jpeg" data-title="Trisomy (Down syndrome)" data-toggle="lightbox" href="https://ghr.nlm.nih.gov/art/large/trisomy.jpeg" target="_blank" title="Image">trisomy 21, which means each cell in the body has three copies of chromosome 21 instead of the usual two copies.

Sex Chromosome Disorders

Sex chromosome (or chromosomal) disorders involve an extra or missing sex chromosome (X or Y). As they involve a sex chromosome, endocrinologic (hormonal) disorders are commonly seen. Turner syndrome (XO) and Klinefelter syndrome (XXY) are sex chromosome disorders. The information that follows is excerpted from the NIH site. 

Turner Syndrome (X0)

Turner syndrome is a chromosomal condition that affects development in females. The most common feature of Turner syndrome is short stature, which becomes evident by about age 5. An early loss of ovarian function (ovarian hypofunction or premature ovarian failure) is also very common. The ovaries develop normally at first, but egg cells (oocytes) usually die prematurely and most ovarian tissue degenerates before birth. Many affected girls do not undergo puberty unless they receive hormone therapy, and most are unable to conceive (infertile). A small percentage of females with Turner syndrome retain normal ovarian function through young adulthood.

This condition occurs in about 1 in 2,500 newborn girls worldwide, but it is much more common among pregnancies that do not survive to term (miscarriages and stillbirths).

Turner syndrome is related to the X chromosome, which is one of the two Credit: Darryl Leja, NHGRIUse of illustrations and other content" data-remote="/art/large/sex-chromosomes-x-and-y.jpeg" data-title="Sex chromosomes (X and Y)" data-toggle="lightbox" href="https://ghr.nlm.nih.gov/art/large/sex-chromosomes-x-and-y.jpeg" target="_blank" title="Image">sex chromosomes. People typically have two sex chromosomes in each cell: females have two X chromosomes, while males have one X chromosome and one Y chromosome. Turner syndrome results when one normal X chromosome is present in a female's cells and the other sex chromosome is missing or structurally altered. The missing genetic material affects development before and after birth.

About half of individuals with Turner syndrome have Use of illustrations and other content" data-remote="/art/large/turner-syndrome-karyotype.jpeg" data-title="Turner syndrome karyotype" data-toggle="lightbox" href="https://ghr.nlm.nih.gov/art/large/turner-syndrome-karyotype.jpeg" target="_blank" title="Image">monosomy X, which means each cell in the individual's body has only one copy of the X chromosome instead of the usual two sex chromosomes.

Most cases of Turner syndrome are not inherited. When this condition results from Use of illustrations and other content" data-remote="/art/large/turner-syndrome-karyotype.jpeg" data-title="Turner syndrome karyotype" data-toggle="lightbox" href="https://ghr.nlm.nih.gov/art/large/turner-syndrome-karyotype.jpeg" target="_blank" title="Image">monosomy X, the chromosomal abnormality occurs as a random event during the formation of reproductive cells (eggs and sperm) in the affected person's parent.

Klinefelter Syndrome (XXY)

Klinefelter syndrome is a chromosomal condition in boys and men that can affect physical and intellectual development. Most commonly, affected individuals are taller than average are unable to father biological children (infertile); however the signs and symptoms of Klinefelter syndrome vary among boys and men with this condition. In some cases, the features of the condition are so mild that the condition is not diagnosed until puberty or adulthood, and researchers believe that up to 75 percent of affected men and boys are never diagnosed.

Boys and men with Klinefelter syndrome typically have small testes that produce a reduced amount of testosterone (primary testicular insufficiency). Testosterone is the hormone that directs male sexual development before birth and during puberty. Without treatment, the shortage of testosterone can lead to delayed or incomplete puberty, breast enlargement (gynecomastia), decreased muscle mass, decreased bone density, and a reduced amount of facial and body hair. As a result of the small testes and decreased hormone production, affected males are infertile but may benefit from assisted reproductive technologies.

Klinefelter syndrome affects about 1 in 650 newborn boys. It is among the most common sex chromosome disorders, which are conditions caused by changes in the number of Credit: Darryl Leja, NHGRIUse of illustrations and other content" data-remote="/art/large/sex-chromosomes-x-and-y.jpeg" data-title="Sex chromosomes (X and Y)" data-toggle="lightbox" href="https://ghr.nlm.nih.gov/art/large/sex-chromosomes-x-and-y.jpeg" target="_blank" title="Image">sex chromosomes (the X chromosome and the Y chromosome).

Klinefelter syndrome is a Credit: Darryl Leja, NHGRIUse of illustrations and other content" data-remote="/art/large/sex-chromosomes-x-and-y.jpeg" data-title="Sex chromosomes (X and Y)" data-toggle="lightbox" href="https://ghr.nlm.nih.gov/art/large/sex-chromosomes-x-and-y.jpeg" target="_blank" title="Image">sex chromosome disorder in boys and men that results from the presence of an extra X chromosome in cells. People typically have National Cancer InstituteUse of illustrations and other content" data-remote="/art/large/normal-human-male-karyotype.jpeg" data-source-href="https://visualsonline.cancer.gov/det...m?imageid=2721" data-title="Normal human male karyotype" data-toggle="lightbox" href="https://ghr.nlm.nih.gov/art/large/no...karyotype.jpeg" target="_blank" title="Image">46 chromosomes in each cell, two of which are the sex chromosomes. Females have two X chromosomes (46,XX), and males have one X and one Y chromosome (46,XY). Most often, boys and men with Klinefelter syndrome have the usual X and Y chromosomes, plus one extra X chromosome, for a total of 47 chromosomes (47,XXY).

Klinefelter syndrome is not inherited; the addition of an extra X chromosome occurs during the formation of reproductive cells (eggs or sperm) in one of an affected person's parents. During Use of illustrations and other content" data-remote="/art/large/mitosismeiosis.jpeg" data-title="Mitosis and meiosis: cell division" data-toggle="lightbox" href="https://ghr.nlm.nih.gov/art/large/mitosismeiosis.jpeg" target="_blank" title="Image">cell division, an error called nondisjunction prevents X chromosomes from being distributed normally among reproductive cells as they form.

This page last updated October 19, 2022.