Autosomal Dominant:

 

Autosomal DominantAutosomal dominant or dominance is a pattern of genetic inheritance that occurs within autosomes (non-sex chromosomes). Their appearance and function are mostly the results of the dominance of one parental gene over the other. From a medical point of view, autosomal dominant disorders represent disorders caused by a single copy of a mutated gene.  Scientists refer to a mutated gene as an allele.  Alleles are carried by both parents and affect both male and female offspring. One copy of the mutation from one parent can cause an autosomal dominant inherited disorder.

Autosomal Dominant vs. Recessive

For a geneticist, the concept of autosomal dominant vs autosomal recessive gene inheritance can easily be understood. The likelihood that a gene will be expressed defines whether a gene is recessive or dominant. A gene is only located on the non-sex chromosomes when it is autosomal. The millions of alleles that make up human DNA’s twenty-two autosomal chromosomal pairs can mutate everywhere. Our chromosomes come paired and we inherit one set from our biological father and one set from our biological mother.

This combination, in which some portions of the genetic code from one parent take priority over the identical genetic information from the other, determines how we appear and how we behave. Our genotype, or genetic makeup, appears incredibly intricate. For instance, there are many distinct alleles involved in determining eye color rather than just one. Our dominant genes, which are typically the outcome of smaller dominant alleles, determine whether the genetic information from our mother or father is expressed. Even if they don’t have a direct impact while dominant alleles exist, recessive alleles can impact subsequent generations.

Fully Dominant vs. Partially Dominant Disorders

Autosomal dominant disorders can be divided into two types: fully dominant and partially dominant. In fully dominant disorders, the mutated gene completely masks the normal gene, causing all individuals carrying the mutated gene to display the characteristics of the disease. This means every carrier exhibits the illness without exception.

In contrast, incomplete dominance, or partially dominant disorders, involves a degree of interaction between the mutated gene and the normal gene. As a result, individuals carrying the mutated gene display varying degrees or types of disease characteristics. This variance can lead to different symptoms or severity levels in individuals, making it a more complex pattern of inheritance.

The Definitions to Fully Understand

Let’s quickly examine the distinctions between a gene, an allele, and a chromosome to make autosomal dominance more understandable. Chromosomes contain an organism’s entire genetic blueprint, made up of information shared by parents. We have exact copies of our parents’ DNA and our DNA contains a mixture of them.

A gene is a length of DNA that determines a genetic trait, such as a propensity to develop a particular type of cancer. We were born with these traits, or damage to our DNA can cause certain traits to form over time. Our genotype is responsible for the characteristics of our DNA. Dominant and recessive genes determine whether these traits are pronounced. The expressed genes (usually dominant genes) give rise to phenotypes (functional or visual traits).

Allele

An extremely particular portion of a gene or chromosome that is located at the same position is known as an allele. Every gene has 2 alleles, one from each parent. While an eye color gene may exist, different alleles will determine the precise color. The alleles determine the blood type you have if one of your genes has the blood type characteristic. Given that several alleles make up a single gene in the case of autosomal dominance, we should really speak of dominant alleles. It has the ability to impact the entire gene, even if just one of tens of thousands of alleles appears damaged.

The afflicted gene is frequently the name of an autosomal dominant (or recessive) ailment. As such, the gene’s related alleles cause the condition. One allele has prevailed over another, according to the definition of the word dominant. A phenotype can occur by a gene with only one copy from one biological parent. But a recessive mutation must pass by both parents. When up against a dominant allele, a recessive allele cannot prevail. The dominant gene in your dark hair originates from your father if both of your parents have brown hair. The brown hair allele is also dominant over a blonde allele in your DNA.

If the male does not have a dominant gene for brown hair, and the female is blond then the children will have blonde hair. When both parents carry the recessive gene, the child will also have blonde hair. This child will have brown hair if it receives a dominant and recessive gene or a group of alleles. Since so many distinct alleles may impact hair color, scientists can rarely anticipate the precise shade of brown.

Carriers

An adult can carry a recessive gene, but it will not result in an identifiable trait (phenotype). Two recessive exact genes will result in the related phenotype when combined with a recessive gene from the other parent. The recessive gene is suppressed when a dominant gene is present. Blonde hair is recessive and dominant in the autosomal dominance scenario from above. Blonde hair gene expression is prevented by the presence of a dominant dark hair gene.

Temporary concealment of an autosomal dominant disease is possible in some circumstances. This means that before we learned about genetic fingerprinting, we believed that some diseases were not genetically caused but rather brought on by the environment. For instance, Huntington’s disease is a progressive autosomal dominant brain condition that impairs cognition, emotion, and movement.  However, only when the gene undergoes a certain stage of mutation. Because Huntington’s gene has not reached the threshold that triggered the symptoms, a parent can pass on the gene without ever having been officially diagnosed with the condition.

Although it is now feasible to detect the presence of a gene long before symptoms show, it is still impossible to forecast whether a person would experience the symptoms or the ailment. We now understand that Huntington’s is a unique form of autosomal dominant illness. One diseased parent will pass on a faulty gene to the affected child, although this parent may not have manifested any symptoms of the illness. Parents cannot carry an autosomal dominant gene.

Symptoms don’t begin to manifest until a specific number of mutations occur. A condition can occur by our surroundings just as much as by the existence of a dominant gene.

Autosomal Dominant Examples

Examples of autosomal dominance can relate to genetic behaviors. For example, it relates to skin, hair, and eye color, the risk of developing certain diseases, and even neurological traits. It shows the odds or odds of inheriting brown, blue, or green eyes from either parent. However, eye color results because of a myriad of alleles and does not always become predictable. As an example, we recommend focusing on individual mutant alleles. This aids in the ability to eliminate the influence of other genetic factors.

Autosomal dominant disorders encompass a wide array of diseases, categorized broadly into several types:

  • Neurological Diseases: These include conditions such as Huntington’s disease, which is discussed in detail below.
  • Musculoskeletal Diseases: Examples include Spondylocostal Dysostosis and Spondyloepiphyseal Dysplasia.
  • Metabolic Diseases: Disorders like metabolic syndrome, which can have genetic components.
  • Tumor Syndromes: Conditions such as Neurofibromatosis Tumors and Marfan Syndrome.

Huntington’s Disease

The huntington protein gene (HTT gene), which appears on chromosome 4, has between 10 and 35 instances of a particular section of code called the CAG trinucleotide repeat. These repeats take place 40 or more times in people with Huntington’s disease. Although it has recently been revealed that repeat expansions can fluctuate in size over the course of one or more generations, this may be inherited. Huntington’s disease does not automatically occur in those who carry the HTT gene.

It has previously been noted that this condition appears as an autosomal dominant disorder with a twist; if the cause of greater repeat expansions is identified, researchers will treat or even eradicate the diseases linked to it. Multiple genetic abnormalities are brought on by repeat expansions. Being an autosomal dominant condition, all it takes for a characteristic to pass along to the next generation is for one parent to have it.

An uppercase letter H in the above figure stands in for the mother’s huntingtin gene. The unshaded squares show that there is no HTT gene (hh) mutation, whereas the gray-shaded boxes signify HTT gene mutation (Hh). The parent with the mutant HTT may not exhibit Huntington’s symptoms and have fewer CAG trinucleotide repeats. This gene is dynamic, so greater repetitions might develop later in life or over the lifetime of any children this parent has.

What causes Huntington’s Disease

Huntington’s disease is a progressive autosomal dominant brain condition that impairs cognition, emotion, and movement. However, only when the gene undergoes a certain stage of mutation. Because Huntington’s gene has not reached the threshold that triggered the symptoms, a parent can pass on the gene without ever having been officially diagnosed with the condition.

Causes of Huntington’s Disease

Huntington’s disease is caused by a mutation in the HTT gene located on chromosome 4. This mutation results in an elongated sequence of the huntingtin protein. Over time, these abnormal proteins accumulate inside nerve cells, disrupting their normal function and eventually leading to cell death through a process called apoptosis.

Symptoms of Huntington’s Disease

The symptoms of Huntington’s disease usually appear in middle age and progressively worsen. They can be broadly categorized into motor, cognitive, and emotional symptoms:

Motor Symptoms:

  • Chorea: Involuntary, dance-like movements involving rapid and unpredictable motions of the fingers, extremities, face, or trunk.
  • Stiffness and Tremors: Known as catalepsy and tremor, these symptoms can significantly impact movement.
  • Coordination Issues: Problems with balance, coordination, and muscle control can make daily activities challenging.
  • Difficulty Swallowing and Speaking: As the disease progresses, these symptoms become more pronounced.

Cognitive Symptoms:

  • Decreased Concentration and Impaired Judgment: These issues can interfere with daily tasks and decision-making.
  • Memory Loss and Learning Difficulties: Affected individuals may struggle with retaining information and learning new skills.
  • Dementia: Severe cognitive impairment can lead to an inability to function independently, drive, or take care of oneself.

Emotional and Behavioral Symptoms:

  • Mood Swings and Personality Changes: These can include impulsiveness, compulsive behavior, anxiety, and depression.
  • Lack of Motivation and Initiative: Individuals may show decreased personal hygiene and empathy.
  • Aggressive and Irritable Behavior: Such changes can strain relationships and social interactions.

Huntington’s disease remains a challenging condition, as symptoms intensify over time, profoundly affecting both the individual and their loved ones. Understanding both its genetic basis and symptomatic progression is crucial for managing the disease effectively.

Polycystic Kidney Disease

It is obvious that half of a Hh and hh parent’s kids are susceptible to the mutant characteristic (Hh). Punnet squares and pedigree charts are terms used to describe diagrams that display hereditary qualities. Another common example of autosomal dominance is polycystic kidney disease. In this disorder, multiple cysts develop in the kidneys and reduce their ability to filter waste products from the blood.

Similar to Huntington’s disease, autosomal dominant polycystic kidney disease (ADPKD) is the product of transmission of the disease from one parent. In this case, a single mutated copy of the PKD1 or PKD2 gene causes disease. PKD1 appears on chromosome 16. PDK2 on chromosome 4. A relatively newly discovered gene on chromosome 11 can cause combined polycystic kidney disease and liver disease. Similar to HD, some cases of ADPKD result in new mutations. Contrary to Huntington’s disease, polycystic kidney disease can also classify as autosomal recessive (ARPKD).

Additional Autosomal Dominant Conditions include:

  • Spondylothoracic Dysostosis
  • Goldenhar Syndrome
  • Cleidocranial Dysplasia
  • Charcot-Marie-Tooth Disease

What Causes Polycystic Kidney Disease

Another common example of autosomal dominance is polycystic kidney disease. In this disorder, multiple cysts develop in the kidneys and reduce their ability to filter waste products from the blood. Similar to Huntington’s Disease, autosomal dominant polycystic kidney disease (ADPKD) is the product of transmission of the disease from one parent. In this case, a single mutated copy of the PKD1 or PKD2 gene causes disease. PKD1 appears on chromosome 16. PDK2 on chromosome 4. A relatively newly discovered gene on chromosome 11 can cause combined polycystic kidney disease and liver disease. Similar to HD, some cases of ADPKD result in new mutations. Contrary to Huntington’s Disease, polycystic kidney disease can also classify as autosomal recessive (ARPKD).

Understanding the Genetic Basis

Polycystic kidney disease (PKD) arises from mutations in one or more genes, notably PKD1, PKD2, and PKHD1. These mutations lead to an abnormal sequence encoding polycystin, a crucial component for maintaining the structure and function of renal tubules. When gene mutations occur, polycystin may be defective or insufficient, impairing normal renal tubule development and operation.

Types and Diagnosis

There are two primary types of PKD:

  • Autosomal Dominant PKD (ADPKD): Typically diagnosed in adulthood.
  • Autosomal Recessive PKD (ARPKD): Can be diagnosed in utero or during infancy.

Symptoms and Complications

The disease is characterized by the growth of numerous fluid-filled cysts on the kidneys. If these cysts become too large or numerous, they can damage the kidneys, reducing their function and potentially leading to kidney failure. PKD can also cause:

  • High Blood Pressure: A common complication.
  • Liver Cysts: Additional cyst formations can occur.
  • Vascular Issues: Problems may arise in the brain and heart.

This extensive impact on the body underscores the importance of understanding both the genetic and symptomatic aspects of PKD.

How is Polycystic Kidney Disease Treated and Managed?

Polycystic Kidney Disease (PKD) management encompasses several key treatment strategies. Each approach focuses on alleviating symptoms, preventing complications, and improving quality of life.

Drug Therapy

One of the primary objectives is to manage high blood pressure, as it exacerbates kidney damage. Medications such as ACE inhibitors and ARBs are often prescribed to maintain blood pressure levels and manage infections when they occur.

Surgical Interventions

Surgical procedures may become necessary to address larger cysts, which can impair kidney function or impact appearance. Additionally, surgery might be required to deal with malignant tumors or to repair aneurysms and dissections. The timing for surgery is typically determined by the cyst’s size, location, and overall impact.

Dialysis and Kidney Transplantation

For patients whose kidney function has declined significantly, dialysis serves as an essential treatment to remove excess water and waste from the bloodstream, effectively acting as an artificial kidney. Kidney transplantation is another option, providing a more permanent solution by replacing the failing kidney. Both treatments necessitate ongoing monitoring and the use of medications to prevent infection or rejection.

Gene Therapy

Gene therapy is an innovative approach under clinical evaluation. It aims to correct the underlying genetic mutations associated with PKD, thereby restoring normal kidney function. This therapy focuses on altering or replacing defective genes to regulate the development and function of renal tubules effectively.

In conclusion, managing PKD involves a comprehensive approach tailored to individual patient needs, utilizing medical, surgical, and potentially groundbreaking genetic therapies to enhance patient outcomes. Regular check-ups and adherence to treatment regimens play a crucial role in effectively managing this condition.

Why choose the Medical City Children’s Orthopedics and Spine Specialists

Medical City Children’s Orthopedics and Spine Specialists with offices in Dallas, Arlington, Frisco, and McKinney, Texas are experts in the management of Autosomal Dominant conditions. We can help patients with Autosomal Dominant conditions because we have the greatest medical professionals and cutting-edge facilities. Get in touch with Medical City Children’s Orthopedics and Spine Specialists as soon as you can and make an appointment for your child.

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National Human Genome Research Institute: Autosomal Dominant Inheritance

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