Down Syndrome PDF

Down Syndrome Disease summary ○ Definition: Down syndrome (DS), also commonly known s trisomy 21, is a chromosome disorder characterized by low intelligence quotient (IQ), dysmorphic facial features, delays in physical development, and a broad array of other mu...

Down Syndrome Disease summary ○ Definition: Down syndrome (DS), also commonly known s trisomy 21, is a chromosome disorder characterized by low intelligence quotient (IQ), dysmorphic facial features, delays in physical development, and a broad array of other multisystem anomalies. ○ All abnormalities are apparently caused by overexpression of specific genes from chromosome 21. ○ The condition may vary in severity from mild to severe. ○ Down syndrome was named after the 19th century English physician John Langdon Down, who described the condition in 1866. Significance: ○ Trisomy 21 is the most common chromosomal abnormality that affects autosomes (i.e., chromosomes that are not sex chromosomes; chromosomes 1–22). ○ The chromosomal aberration also represents the single most common cause of birth defects and is a major cause of mental retardation today. ○ Down syndrome accounts for approximately one third of all moderate and severe mental handicaps in school-aged children. ○ A significant number of adults with DS cannot lead totally independent lives due to a low IQ. ○ IQ typically spans a range of 20–85 with a mean value of approximately 50. Advanced maternal age remains the only well-established risk factor for DS. ○ The frequency of DS increases with advancing maternal age ○ It has long been recognized and strongly emphasized that the risk for giving birth to a child with DS increases markedly at maternal age 35 years and beyond. ○ However, it is worth noting here that the majority of children with DS (80%) are born to women younger than 35 years of age because most pregnancies occur in this age group. ○ In 95% of cases of trisomy 21, the extra chromosome 21 has a maternal origin; however, some studies have reported a correlation with advanced paternal age Pathophysiology: ○ Three specific cytogenetic abnormalities cause Down syndrome: trisomy 21, chromosomal translocation, and mosaicism. ○ Trisomy 21 results from a pathophysiologic process known as non-disjunction in which faulty cell division occurs and chromosomes fail to separate during oogenesis or spermatogenesis. ○ Non-disjunction gives rise to germ cells with an even number of chromosomes (either 22 or 24). ○ The products of conception that result from fusion of an abnormal germ cell with a normal one have an uneven number of chromosomes, either 45 or 47. ○ The extra chromosome 21 is replicated with every cell division as the embryo and fetus grows. ○ When nondisjunction occurs during oogenesis, it occurs three times more frequently during the first stage of meiosis (i.e., meiosis I) than during meiosis II. ○ It is not clearly known why advanced maternal age is associated with nondisjunction.  ○ However, the dramatic increase in risk for trisomy 21 in the fourth decade of life may be the result of the age of maternal egg cells, which are held in an arrested state of prophase I from the time that they are formed in the female embryo until they are extruded from the ovaries during ovulation Diagnosis Clinical Manifestations and Laboratory Tests. ○ Down syndrome is usually identified at birth or shortly thereafter. ○ Initially, the diagnosis is based on physical characteristics that are common to babies with DS. ○ Individually these features may be subtle, but together they comprise a syndrome that permits diagnosis. ○ Not all children with DS have the same characteristics and abnormalities may range from mild to severe, but some anomalies are common. ○ These include: poor muscle tone (i.e., hypotonia) with decreased response to normal stimuli a single crease across the palm of the hand (i.e., simian crease) a slightly flattened facial profile an upward slanting of the eyes ○ The forehead may be sloping, the nasal bridge is broad and flat, and the inner corner of the eyes may have a rounded fold of skin (i.e., epicanthal fold) rather than coming to a point. ○ Interocular distance may be increased (i.e., hypertelorism). ○ An unusual ring of tiny white spots around the iris of the eye and known as Brushfield spots is common. ○ The head may be smaller than normal (i.e., microcephaly) and abnormally shaped. ○ The occiput (i.e., back of the head) is often flat rather than rounded. ○ The mouth is usually small and open and the tongue is large (i.e., macroglossia) and furrowed with a tendency to protrude. ○ Ears are typically small, low-set on the head, and malformed. ○ The hands are broad with relatively short fingers (i.e., brachydactyly) and the finger joints are hyperextensible ○ Hearing tests are also appropriate, as two of three children with DS have some degree of abnormal hearing. ○ A definitive diagnosis is only established by a chromosome study known as karyotyping. ○ A karyotype is a visual display of the patient’s chromosomes organized by size, number, and distinct banding patterns. ○ The majority of patients will have simple trisomy 21. ○ However, newborns with a translocation involving chromosome 21 may have inherited the cytogenetic pattern from a parent, in which case there is a substantial recurrence risk for DS in subsequent offspring. ○ Two types of procedures are available to pregnant women for detecting DS: screening tests and diagnostic tests. ○ Screening tests help to determine the probability that a baby has DS. ○ Diagnostic tests determine whether or not the baby definitively has DS.  ○ Three diagnostic tests are currently available for gathering cells upon which chromosome studies can be performed. ○ With chorionic villus sampling (CVS), cells taken from the mother’s placenta can be used to analyze fetal chromosomes. ○ CVS is typically conducted between 10–13 weeks of gestation, carries a risk for miscarriage up to 1 in 100, and has an accuracy greater than 95%. ○ Amniocentesis is the criterion standard of invasive diagnostic tests for DS. ○ With amniocentesis, a sample of the amniotic fluid surrounding the fetus is withdrawn with a needle inserted into the mother’s uterus. Prompt treatment of respiratory tract and middle ear infections is also necessary. ○ Timely surgery of cardiac malformations, which frequently present during the first 6 months of life, may be required to prevent serious complications. ○ Prompt surgical repair of gastrointestinal anomalies, such as duodenal atresia, is imperative. ○ Surgical removal of enlarged adenoids may be performed when the patient demonstrates obstructive sleep apnea. ○ When spinal cord compression occurs, surgical intervention may be necessary to stabilize the spine. ○ Congenital cataracts must be removed soon after birth to permit light to reach the retina. ○ Subsequently, appropriate correction with glasses or contact lenses often assures adequate vision. ○ Early intervention programs for infants aged 0–3 years are designed to comprehensively monitor and enrich development. ○ Such programs focus on feeding, gross and fine motor development, and development of language, personal, and social skills. ○ Social quotient may also be improved through early intervention. ○ Positive developmental changes are possible, particularly in terms of the patient’s independence, ability to function in the community, and quality of life. ○ Since babies with DS do not have good muscle tone,a physical therapist may help infants learn to roll over, sit up, and walk. ○ Since parents of a child with DS are at increased risk for having another child with the condition, genetic counseling is recommended. ○ If a couple has a child with trisomy 21, the recurrence risk is approximately 1%. ○ De novo translocations carry a recurrence risk of 2–3%. ○ Approximately 12% of the progeny of translocation carrier mothers and 3% of translocation carrier fathers are born with DS. ○ In the rare case that a carrier parent has a 21q21q translocation, recurrence risk is 100%