Genetic Disorders

A genetic disorder is a genetic problem caused by one or more abnormalities formed in the genome. Most genetic disorders are quite rare and affect one person in every several thousands or millions. Genetic disorders may be hereditary, meaning that they are passed down from the parents’ genes. In other genetic disorders, defects may be caused by new mutations or changes to the DNA. In such cases, the defect will only be passed down if it occurs in the germ-line.

Gene related disorders Autosomal dominant disorders

Autosomal Dominant – A pattern of inheritance in which an affected individual has one copy of a mutant gene and one normal gene on a pair of autosomal chromosomes. (In contrast, autosomal recessive diseases require that the individual have two copies of the mutant gene.)

Types:-

Chondrodystropic dwarfism– A congenital dwarfism in which the disturbed development of the cartilage of the long bones arrests the growth of long bones, resulting in extremely shortened extremities. People with chondrodystrophy have a normal-sized trunk and abnormally short limbs and extremities (dwarfism). Those affected with the disorder often call themselves dwarfs, little people or short-statured persons. Over 100 specific skeletal dysplasias have been identified. Chondrodystrophy is found in all races and in both females and male and occurs in around one of every 25,000 children.

Myotonic muscular dystrophy– Myotonic dystrophy (DM) is a form of muscular dystrophy that affects muscles and many other organs in the body. The term “muscular dystrophy” means progressive muscle degeneration, with weakness and shrinkage of the muscle tissue. DM is divided into two types;

  • Type 1 DM (DM1), long known as Steinert disease, occurs when a gene on chromosome 19 called DMPK contains an abnormally expanded section located close to the regulation region of another gene, SIX5.
  • Type 2 DM (DM2), recognized in 1994 as a milder version of DM1, is caused by an abnormally expanded section in a gene on chromosome 3 called ZNF9. DM2 was originally called PROMM, for proximal myotonic myopathy, a term that has remained in use but is somewhat less common than the term DM2.

Huntington’s disease– An inherited condition in which nerve cells in the brain break down over time.It typically starts in a person’s 30s or 40s. Usually, Huntington’s disease results in progressive movement, thinking (cognitive) and psychiatric symptoms.No cure exists, but drugs, physiotherapy and talk therapy can help manage some symptoms.

Neurofibromatosis– A condition that causes tumors to form in the brain, spinal cord and nerves. Neurofibromatosis is usually non-cancerous. There are three types of this condition.

  • Type 1 usually appears in childhood, while Types 2 and 3 appear in early adulthood.
  • Type 1 can cause bone deformities, learning disabilities and high blood pressure.
  • Type 2 can cause hearing loss, vision loss and difficulty with balance.
  • Type 3 can cause chronic pain throughout the body.
  • Some cases may not require treatment other than careful observation. Other cases may require chemotherapy, radiation therapy or surgery.

Hypercholesterolemia– High amounts of cholesterol in the blood. High cholesterol can limit blood flow, increasing the risk of a heart attack or stroke. It’s detected by a blood test. High cholesterol has no symptoms. Treatments include medication, a healthy diet and exercise.

Retinoblastoma- An eye cancer that begins in the back of the eye (retina), most commonly in children. It may occur in one or both eyes. It has few, if any, symptoms at first. It may be noticed if a pupil appears white when light is shone into the eye, sometimes with flash photography. Eyes may appear to be looking in different directions. Treatments include chemotherapy, radiation and laser therapy.

Autosomal recessive disorders – To have an autosomal recessive disorder, you inherit two mutated genes, one from each parent. These disorders are usually passed on by two carriers. Their health is rarely affected, but they have one mutated gene (recessive gene) and one normal gene (dominant gene) for the condition.

Types:

Cystic Fibrosis – An inherited life-threatening disorder that damages the lungs and digestive system.It affects the cells that produce mucus, sweat and digestive juices. It causes these fluids to become thick and sticky. They then plug up tubes, ducts and passageways. Symptoms vary and can include cough, repeated lung infections, inability to gain weight and fatty stools.
Treatments may ease symptoms and reduce complications. Newborn screening helps with early diagnosis.

Sickle cell disease – A group of disorders that cause red blood cells to become misshapen and break down. With sickle cell disease, an inherited group of disorders, red blood cells contort into a sickle shape. The cells die early, leaving a shortage of healthy red blood cells (sickle cell anaemia) and can block blood flow causing pain (sickle cell crisis). Infections, pain and fatigue are symptoms of sickle cell disease.Treatments include medication, blood transfusions and rarely a bone-marrow transplant.

Thalassaemia – A blood disorder involving lower-than-normal amounts of an oxygen-carrying protein. Thalassemia is an inherited blood disorder characterized by less oxygen-carrying protein (haemoglobin) and fewer red blood cells in the body than normal.
Symptoms include fatigue, weakness, paleness and slow growth. Mild forms may not need treatment. Severe forms may require blood transfusions or a donor stem-cell transplant.

Alkaptonuria (black urine disease) – Alkaptonuria, or “black urine disease”, is a very rare inherited disorder that prevents the body fully breaking down two protein building blocks (amino acids) called tyrosine and phenylalanine. It results in a build-up of a chemical called homogentisic acid in the body.

Phenylketonuria – A birth defect that causes an amino acid called phenylalanine to build up in the body. Newborns should be screened for PKU. Untreated phenylketonuria can lead to brain damage, intellectual disabilities, behavioral symptoms or seizures. Treatment includes a strict diet with limited protein.

Albinism – Albinism is a rare group of genetic disorders that cause the skin, hair, or eyes to have little or no color. Albinism is also associated with vision problems. According to the National Organization for Albinism and Hypopigmentation, about 1 in 18,000 to 20,000 people in the United States have a form of albinism.

Tay-Sachs Disease – A rare, inherited disorder that destroys nerve cells in the brain and spinal cord. Tay-Sachs disease is typically found in people with certain ancestry, such as Eastern European Jews. A fatty substance in the brain destroys nerve cells. Symptoms of slowed development usually appear around six months of age. Symptoms progress until they lead to death, often around age four. There is no cure for Tay-Sachs disease, but research is ongoing.

Gaucher,s disease – Gaucher disease is an inherited condition (passed down through families). It is a lysosomal storage disorder, a type of disease that causes fatty substances to build up in the bone marrow, liver and spleen. The fatty substances (sphingolipids) weaken bones and enlarge the organs, so they can’t work like they should.

Galactosemia – Galactosemia is a rare, hereditary disorder of carbohydrate metabolism that affects the body’s ability to convert galactose (a sugar contained in milk, including human mother’s milk) to glucose (a different type of sugar).

Sex linked dominant disorders – Sex-linked dominant is a rare way that a trait or disorder can be passed down through families. One abnormal gene on the X chromosome can cause a sex-linked dominant disease.

Types:

Fragile X-syndrome – A genetic condition causing intellectual disability. Fragile X syndrome causes mild to severe intellectual disability. It affects both males and females, but females usually have milder symptoms. Symptoms include delays in talking, anxiety and hyperactive behaviour. Some people have seizures. Physical features might include large ears, a long face, a prominent jaw and forehead and flat feet. Therapy can be used to treat learning disabilities. Medication may be used to treat anxiety and mood disorders.

Vitamin-D resistant rickets – Hypophosphatemic rickets (previously called vitamin D-resistant rickets) is a disorder in which the bones become painfully soft and bend easily, due to low levels of phosphate in the blood. Symptoms usually begin in early childhood and can range in severity

Sex linked recessive disorders

Types:

Haemophilia (Bleeder’s Disease) – Hemophilia is usually an inherited bleeding disorder in which the blood does not clot properly. This can lead to spontaneous bleeding as well as bleeding following injuries or surgery. Blood contains many proteins called clotting factors that can help to stop bleeding.

Red green Colour blindness – Red-green color blindness is the most common type of color deficiency. Also known as deuteranopia, this is most likely a congenital condition, meaning that you’re born with it. If you have this type of color blindness, you may have difficulty seeing different shades of red, green, and yellow.

X linked Ichthyosis (XLI) – X-linked ichthyosis (abbreviated XLI) is a skin condition caused by the hereditary deficiency of the steroid sulfatase (STS) enzyme that affects 1 in 2000 to 1 in 6000 males. XLI manifests with dry, scaly skin and is due to deletions or mutations in the STS gene.

Chromosome disorder – An abnormal condition due to something unusual in an individual’s chromosomes. For example, Down syndrome is a chromosome disorder caused by the presence of an extra copy of chromosome 21, and Turner syndrome is most often due to the presence of only a single sex chromosome: one X chromosome.

Autosomal Trisomy in Human beings

Types:-

Down syndrome (trisomy of 21st chromosomes) – A genetic chromosome 21 disorder causing developmental and intellectual delays. Down’s syndrome is a genetic disorder caused when abnormal cell division results in extra genetic material from chromosome 21. Down’s syndrome causes a distinct facial appearance, intellectual disability and developmental delays. It may be associated with thyroid or heart disease. Early intervention programmes with a team of therapists and special educators who can treat each child’s specific situation are helpful in managing Down’s syndrome.

Edward Syndrome (trisomy of 18th chromosomes) – A condition that causes severe developmental delays due to an extra chromosome 18. A first-trimester screening that includes a blood test and ultrasound offers early information about a baby’s risk of having it. A second trimester blood test called a quad screen can also detect it. Symptoms include low birth weight, small abnormally shaped head and birth defects in organs that are often life threatening. Edwards’ syndrome has no treatment and is usually fatal before birth or within the first year of life.

Patau syndrome (trisomy of 13th chromosomes) – A condition in which a person has an extra chromosome 13. Prenatal testing can detect Patau syndrome during pregnancy. Patau syndrome causes severe intellectual disability and physical defects. Most infants with this condition don’t live past their first week of life. Treatment varies from child to child and focuses on relieving symptoms and managing complications.

Deletion in Chromosomes – In genetics, a deletion (also called gene deletion, deficiency, or deletion mutation) (sign: Δ) is a mutation (a genetic aberration) in which a part of a chromosome or a sequence of DNA is lost during DNA replication. Any number of nucleotides can be deleted, from a single base to an entire piece of chromosome.

Types:-

Cri-Du-chat Syndrome Cri du chat syndrome is a rare genetic disorder due to a partial chromosome deletion on chromosome 5. Its name is a French term (“cat-cry” or “call of the cat”) referring to the characteristic cat-like cry of affected children.

Wolf-Hirschhorn Syndrome(WHS) – Wolf-Hirschhorn syndrome (WHS) is a genetic disorder that affects many parts of the body. The major features include a characteristic facial appearance, delayed growth and development, intellectual disability , low muscle tone ( hypotonia ), and seizures.

Translocation in chromosomes – In genetics, chromosome translocation is a phenomenon that results in unusual rearrangement of chromosomes. This includes balanced and unbalanced translocation, with two main types: reciprocal-, and Robertson Ian translocation.

Types:-

Chronic myelogenous Leukemia (CML Ttanslocation between 9th and 22nd chromosomes) – A slowly progressing and uncommon type of blood-cell cancer that begins in the bone marrow. Chronic myeloid leukaemia typically affects older adults. It’s caused by a chromosome mutation that occurs spontaneously. Doctors aren’t sure what causes the mutation.Many people don’t develop symptoms until later stages and the diagnosis is only made through routine blood work. When symptoms do occur, they include bleeding easily, feeling run down or tired, weight loss, pale skin and night sweats. Treatments include targeted drugs, stem-cell transplant, chemotherapy and biological therapy.

Burkitt’s Lymphoma (Translocation between 8th and 14th chromosomes) – Burkitt lymphoma (BL) is a very fast-growing type of cancer. It is a form of B-cell non-Hodgkin’s lymphoma. Signs and symptoms may differ depending on the form of BL and the organs or body systems involved. When it spreads, weakness and fatigue often develop. Lymphoma cells may build up in the lymph nodes and other organs, causing swelling.

Sex chromosomes linked Disorders – It can be either an autosomal chromosome or a sex chromosome. Sex-linked diseases are inherited through one of the sex chromosomes, which are the X and Y chromosomes. Dominant inheritance occurs when an abnormal gene from one parent can cause a disease, even though a matching gene from the other parent is normal.

Types:-

Turner syndrome( X – monosomy = 44+ XO) – A chromosomal disorder in which a female is born with only one X chromosome
Turner syndrome results from a missing or incomplete sex chromosome. Symptoms include short stature, delayed puberty, infertility, heart defects and certain learning disabilities. Treatment involves hormone therapy. Fertility treatment may be necessary for women who want to become pregnant.

Klinefelter Syndrome (extra X- chromosomes along with Y- chromosomes) – 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.

Jacobs syndrome ( XYY- with Extra Y- chromosomes) – Males with XYY syndrome have 47 chromosomes because of the extra Y chromosome. This condition is also sometimes called Jacob’s syndrome, XYY karyotype, or YY syndrome. According to the National Institutes of Health, XYY syndrome occurs in 1 out of every 1,000 boys.

Poly X females or Triplo X (with Extra X- chromosomes) – An abnormality resulting in an extra X chromosome in some females.Triple X syndrome is usually caused by malformation of an egg or sperm cell or by an error early in embryo development.
Many women have few or no symptoms. In most cases, no treatment is required. Those who experience developmental delays and learning disabilities may require intervention, such as counselling.

Diagnosis

Due to the wide range of genetic disorders that are known, diagnosis is widely varied and dependent of the disorder. The basic aspects of a genetic disorder rests on the inheritance of genetic material. With an in depth family history, it is possible to anticipate possible disorders in children which direct medical professionals to specific tests depending on the disorder and allow parents the chance to prepare for potential lifestyle changes, anticipate the possibility of stillbirth, or contemplate termination Prenatal diagnosis can detect the presence of characteristic abnormalities in foetal development through ultrasound, or detect the presence of characteristic substances via invasive procedures which involve inserting probes or needles into the uterus such as in amniocentesis.

Prognosis

Not all genetic disorders directly result in death; however, there are no known cures for genetic disorders. Many genetic disorders affect stages of development, such as Down syndrome, while others result in purely physical symptoms such as muscular dystrophy. Other disorders, such as Huntington’s disease, show no signs until adulthood. During the active time of a genetic disorder, patients mostly rely on maintaining or slowing the degradation of quality of life and maintain patient autonomy. This includes physical therapy, pain management, and may include a selection of alternative medicine programs.

Treatment

The treatment of genetic disorders is an ongoing battle with over 1800 gene therapy clinical trials having been completed, are ongoing, or have been approved worldwide. Despite this, most treatment options revolve around treating the symptoms of the disorders in an attempt to improve patient quality of life. Gene therapy refers to a form of treatment where a healthy gene is introduced to a patient. This should alleviate the defect caused by a faulty gene or slow the progression of disease. A major obstacle has been the delivery of genes to the appropriate cell, tissue, and organ affected by the disorder. How does one introduce a gene into the potentially trillions of cells which carry the defective copy? This question has been the roadblock between understanding the genetic disorder and correcting the genetic disorder.

Conclusion

Genetic disorders are a topic in biology that cannot be avoided. The fact is that genetic disorders can happen in humans, plants or animal. No one and nothing is safe from a genetic disorder. A genetic disorder can appear in the first years off life, or can appear much later in life when least expected. A basic principal of biology states that the behaviour of chromosomes during the meiosis process can account for genetic inheritance patterns.