Genetic Disorders

Achondroplasia

Mode of Inheritance: Autosomal Dominant

Common name- short limbed dwarfism Symptoms

Incidence:
Occurs equally in males and females and in all races 1/25,000 children

Cri Du Chat

Symptoms
high-pitched cry sounds like a cat (for which the syndrome was named) low birth weight and slow growth small head (microcephaly) wide-set eyes (hypertelorism) downward slant to the eyes (palpebral fissures) small jaw (micrognathia) low-set ears (may be malformed) partial webbing or fusing of fingers or toes single line in the palm of the hand (simian crease) mental retardation slow or incomplete development of motor skills

Mode of Inheritance - Spontaneous deletion of segment of chromosome 5 Incidence: between 1/20000 and 1/50000 babies Prognosis: dependent on the severity of mental retardation

Cystic Fibrosis

Symptoms: Chronic lung problems Digestive disorders Lungs are covered with a thick sticky mucus which is hard to remove. This promotes bacterial infections. The reason the mucus is thick, is that the body is unable to transport water and salt across the cell membrane

Mode of Inheritance: Autosomal recessive for CFTR gene Most common in Europeans

Diagnosis

People with cystic fibrosis have 2-5 times the normal amount of salt in their sweat. Doctors use a sweat test to measure the amount of salt in a person's sweat. Sweat is collected from the arm or leg and taken to a laboratory to be analyzed. In newborns, doctors measure the amount of a protein called trypsinogen in the blood. The level is higher in people with CF. Finally, genetic tests can identify a faulty CFTR gene using a sample of the patient's blood. There is no cure for cystic fibrosis. Common treatments are: Chest physical therapy, in which the patient is repeatedly clapped on the back to free up mucous in the chest Inhaled antibiotics to kill the bacteria that cause lung infections Bronchodilators (also used by people with asthma) that help keep the airways open Pancreatic enzyme replacement therapy to allow proper food digestion Gene therapy (a treatment currently in clinical trials), in which the healthy CFTR gene is inserted into the lung cells of a patient to correct the defective gene.

Treatment

Duchene Muscular Dystrophy

Symptoms:

Gradual wasting away of skeletal muscle Progressive and increased weakness and loss of muscle mass and function Noticed before age 5 Pelvic and trunk muscles are affected 1st
This results in spinal deformaties and a waddling gate Death usually occurs because of respiratory weakness and wasting away of the heart muscle

Mode of Inheritance - X linked recessive, boys are mostly affected Treatment: Treatment may include physical therapy, respiratory therapy, speech therapy, orthopedic appliances used for support, and corrective orthopedic surgery. Drug therapy can slow muscle degeneration, control seizures and some muscle activity, delay some damage to dying muscle cells, and fight respiratory infections. Some patients may need assisted ventilation to treat respiratory muscle weakness and a pacemaker for cardiac abnormalities. Prognosis: The prognosis for people with MD varies according to the type and progression of the disorder. Some cases may be mild and progress very slowly over a normal lifespan, while others produce severe muscle weakness, functional disability, and loss of the ability to walk. Some children with MD die in infancy while others live into adulthood with only moderate disability.

Fibrodysplasia ossificans progressiva

rare genetic disease that causes muscle to be turned into bone. Mode of Inheritance: autosomal dominant, but most cases are sporadic. Symptoms: any small injury to connective tissue (muscles, ligaments, and tendons) can result in the formation of hard bone around the damaged site. Children are born with a characteristic malformation of the great toes and begin to develop heterotopic (extra) bone formation during early childhood.

Fragile X syndrome
Symptoms: Intellectual difficulties; mental retardation; patients have a long, narrow face; prominent ears, jaw and forehead, loose joints; patients usually avoid eye contact; Emotional and behavioral problems are common such hand-biting, and hand flapping is common Common inherited cause of mental retardation The name comes from the broken appearance of the X chromosome in people with the disease.

Mode of Inheritance: X linked recessive results in a break or weakness on the long arm of the X chromosome Treatment: There is no cure for fragile X syndrome. special education, speech and language therapy, occupational therapy and behavioral therapies are helpful in addressing many of the behavioral, and cognitive issues in fragile X syndrome. medications can be helpful for aggression, anxiety, hyperactivity and poor attention span. Testing The Southern Blot analysis -this determines if the gene has a full mutation and its approximate size, if the gene has been methylated and if there is mosaicism (a mixture of different cell types). The polymerase chain reaction (PCR) analysis can determine the actual number of repeats in individuals with a normal size gene or with a premutation. It is not the test of choice to diagnose a full mutation, but is quite accurate in determining premutation and normal gene repeat numbers.

Klinefelters Syndrome
Symptoms: have internal male ducts and genitalia; but underdeveloped testes that fail to produce sperm; feminine sexual development is not suppressed, so these men have slightly developed breasts Mode of Inheritance: Trisomy of sex chromosome XXY Remember these result due to nondisjunction during meiosis

Diagnosis:
diagnosed in adulthood using a karyotype, an analysis of the patient's chromosomes taken from a blood sample. also be diagnosed during a woman's pregnancy. Doctors can look for the chromosome abnormality in cells taken from the amniotic fluid that surrounds the fetus (amniocentesis), or from the placenta (chorionic villus sampling (CVS)).

Treatment

Hormone replacement therapy is the best way to treat this disorder. Teenagers are typically given testosterone injections to replace the hormone that would normally be produced by the testes. Synthetic testosterone works like natural testosterone - it builds muscle and increases hair growth.

Symptoms A connective tissue disorder involving collagen; may affect the heart, blood vessels, lungs, eyes, bones, and ligaments. Patients are tall slender, loose jointed have sclerosis, and the breastbone is usually caved in. The face is long and narrow and the roof of the mouth is high, and the teeth are crowded. The heart frequently murmurs, the aorta is weak, and nearsightedness is very common Mode of Inheritance Autosomal daominant It is thought that Abraham Lincoln had Marfan Syndrom Treatment - no cure for the Marfan syndrome. Medication Beta-blocker medications have been shown to slow enlargement of the aorta and delay aortic surgery. Heart surgery Lifestyle changes Lifestyle changes, such as avoiding strenuous exercise and contact sports, can help contribute to living with Marfan syndrome.

Marfan Syndrome

Neurofibromatosis

NF1 affects the peripheral nervous system and NF2 affects the central nervous system Mode of inheritance: NF1 is caused by a mutation on chromosome 17 and NF2 is caused by a mutation on chromosome 22 Symptoms NF2- Growth around the vestibular nerve of the ear which causes deafness and in central nervouse system, brain, and spinal cord NF1- Pigmented spots on skin and bone abnormalities Treatments- surgeries to remove growths

Osteogenisus Imperfecta

genetic disorder characterized by bones that break easily, often from little or no apparent cause. caused by a genetic defect that affects the bodys production of type I collagen. Collagen is the major protein of the bodys connective tissue and can be likened to the framework around which a building is constructed. It is often, though not always, possible to diagnose OI based solely on clinical features. Clinical geneticists can also perform biochemical (collagen) or molecular (DNA) tests that can help confirm a diagnosis of OI in some situations. These tests generally require several weeks before results are known. Both the collagen biopsy test and DNA test are thought to detect almost 90% of all type I collagen mutations. A positive type I collagen study confirms the diagnosis of OI, but a negative result leaves open the possibility that either a collagen type 1 mutation is present but was not detected or the patient has a form of the disorder that is not associated with collagen type 1 mutations. Therefore, a negative type I collagen study does not rule out OI.

Phenylketonuria PKU
Phenylketonuria is a rare metabolic disorder that affects the way the body breaks down protein. If not treated shortly after birth, PKU can be destructive to the nervous system, causing mental retardation. PKU is caused by a mutation in a gene on chromosome 12. The gene codes for a protein called PAH (phenylalanine hydroxylase), an enzyme in the liver. This enzyme breaks down the amino acid phenylalanine into other products the body needs. When this gene is mutated, the shape of the PAH enzyme changes and it is unable to properly break down phenylalanine. Phenylalanine builds up in the blood and poisons nerve cells (neurons) in the brain. Mode of Inheritance Autosomal recessive

Diagnosis

Because PKU must be treated early, babies in every U.S. state are routinely tested for the disease. A small blood sample is taken from the baby's heel or arm and checked in a laboratory for high levels of phenylalanine. People who have PKU must eat a protein-free diet, because nearly all proteins contain phenylalanine. Infants are given a special formula without phenylalanine. Older children and adults have to avoid protein-rich foods such as meat, eggs, cheese, and nuts. They must also avoid artificial sweeteners with aspertame, which contains phenylalanine.

Treatments:

Prader-Willi Syndrome

complex genetic disorder that typically causes low muscle tone, short stature, incomplete sexual development, cognitive disabilities, problem behaviors, and a chronic feeling of hunger that can lead to excessive eating and life-threatening obesity. due to lack of several genes on one of an individuals two chromosome 15s the one normally contributed by the father. In the majority of cases, there is a deletionthe critical genes are somehow lost from the chromosome. In most of the remaining cases, the entire chromosome from the father is missing and there are instead two chromosome 15s from the mother (uniparental disomy). Mode of Inheritance: spontaneous genetic mutation

Sickle Cell Anemia

A red blood cell disorder where cells become hard and sticky; they appear to look like sickles. They clog the flow of blood and often break apart , causing severe pain, damage, and low blood count (anemia). The cells sickle because there is a change in the hemoglobin to form long rods when oxygen is given up. Mode of Inheritance autosomal recessive

Diagnosis: tests can show if the newborn infant has sickle cell anemia or carries the sickle cell trait. If the test shows that the sickle-shaped hemoglobin is present, a second blood test is done to confirm the diagnosis. sample of amniotic fluid or tissue taken from the placenta. This test can be done as early as the first few months of pregnancy.

Treatments:

A bone marrow transplant is the only cure The drug hydroxyurea lessens complications Blood transfusions Narcotics for pain

Tay Sachs

Symptoms: Mental retardation, infants become weak and have a difficult time eating, loss of motor function; a delay in learning to sit or stand; a typical cherry red spot on the retina; at 12 months there is a decrease in mental and motor functions , onset of blindness, deafness, rigidity and brain enlargement; death usually occurs by age 3 by pneumonia or lung infection Mode of Inheitance autosomal recessive Prevalent in Jews of Eastern-European descent Treatments

No cure Treatment of the late onset form of Tay-Sachs with a ganglioside synthesis inhibitor

Trisomy 21 Down Syndrome

Symptoms

Small stature Mild to moderate mental retardation Delayed mental and motor development Smaller ears and mouth Smaller hands and feet Decreased muscle tone Gap between 1st and 2nd toes

Mode of Inheritance

95% have trisomy 21 Remember: this means that the individual has 47 chromosomes in each cell rather than 46. 3-4% have a translocation or an extra chromosome attached to another chromosome typically 14,21, or 22.

Trisomy 18 Edwards Syndrome

Symptoms
Infants are small with elongated skulls ears are set low and are malformed webbed neck congenital dislocation of hips receding chin

Prognosis: Survival time is normally less than 4 months. Death usually occurs from pneumonia or heart failure. Mode of Inheritance: Trisomy 18 Incidence: 1/11,000, 80% are females

Trisomy 13 Patau Syndrome

Symptoms: Infants are not mentally alert; thought to be deaf; tend to have a hairlip; cleft palates are also common; polydactly; congenital malformation of most organ systems Most embryos with trisomy 13 do not survive gestation and are spontaneously aborted. Of those surviving to term gestation, approximately 82-85% do not survive past 1 month , and 85-90% do not survive past 1 year of age. Of those infants that survive past 1 year, most have few major malformations, but the prognosis remains poor. There have been 5 cases reported in the medical history of patients living beyond 10 years of age.

Turner Syndrome
Symptoms: females are short in stature , infertile; there is no connection with mental retardation, only learning difficulties; skeletal abnormalities, heart and kidney abnormalities; thyroid disfunction; the external genitalia are female, but the ovaries are rudimentary Mode of Inheritance Monosomy; nondisjunction of sex chromosomes during meiosis Complete are partial absence of two X chromosomes (XO); mostly resulting in missing genetic material on the X chromosome;

Diagnosis

blood sample can be used to make a karyotype (a chromosome analysis) and the diagnosis can be confirmed. during pregnancy with a chorionic villus sampling (CVS) or amniocentesis. Alternatively, an ultrasound (a machine that uses sound waves to look inside a mother's uterus) can identify the disorder by its physical symptoms before the baby is born. Hormone replacement therapy is the best way to treat this disorder. Teenagers are treated with growth hormone to help them reach a normal height. They may also be given low doses of androgens (male hormones which females also produce in small quantities) to increase height and encourage normal hair and muscle growth. Some patients may take the female hormone estrogen to promote normal sexual development.

Treatment