Pediatrics Chapter 32: Genetic disorders

Sex chromosome abnormalities occur when there is a:

-A missing or extra sex chromosome. -Abnormalities in sexual development, fertility, and growth and deficits in behavior and learning are common. -These disorders include Turner syndrome and Klinefelter syndrome.

Genetic testing:

-A series of tests conducted during pregnancy that assess for genetic changes, or mutations, in the fetus indicative of a genetic disorder.

Mosaic Down syndrome:

-A variant of this condition, is also not inherited and occurs because of a random event during cell division, resulting in some of the body's cells having two copies of chromosome 21 and others having three copies of chromosome 21.

Evaluation:

-Although there is no cure for PKU, the prognosis is good as long as the child complies with a diet low in phenylalanine and maintains blood levels of phenylalanine in the therapeutic range.

Evaluation:

-Although there is no cure for Turner syndrome, the prognosis is good, and care focuses on managing the health issues that may occur with the syndrome.

Evaluation:

-Although there is no cure for fragile X syndrome, the prognosis is good, with a normal life span expected.

Fragile X syndrome:

-An inherited, genetic condition that is caused by a mutation in the X chromosome and that is the most common known cause of intellectual disability.

- Complications include:

-Apnea -Deafness -Feeding problems -Heart failure, seizures -Vision problems -Intellectual disability -Developmental delays -Increased risk for cancers

Care for these children involve:

-Are often involves the assessment and treatment of multiple organ systems. -Genetic disorders do not have specific treatments or cures. -Treatment focuses on symptomatic care, supportive care, and prevention of complications related to the disorder.

Multifactorial inheritance disorders:

-Are thought to be caused by multiple gene and environmental factors. -Many common congenital malformations such as cleft lip, cleft palate, clubfoot, and cardiac defects are attributed to multifactorial inheritance.

Spinal problems:

-Atlantoaxial instability of the first and second cervical vertebrae -Risk of serious injury to the spinal cord from overextension of the neck -Cervical X-rays

Immune disorders:

-Autoimmune disorders, some forms of cancer (leukemia), infectious diseases (pneumonia), recurrent or chronic respiratory infections, otitis media -Laboratory values

Examples of these disorders include:

-Carnitine deficiency -Kearns-Sayre syndrome (a multisystem disorder) -Leukodystrophy (a neurological disorder).

Clinical Presentation:

-Cleft lip and palate and extra digits -Clenched hands (with outer fingers on top of inner fingers) -Close-set eyes, hernias -Low-set ears -Scalp defects (such as missing skin) -A single palmar crease -Limb abnormalities -Microcephaly -Micrognathia (small lower jaw) -Undescended testicles

Heart defects:

-Congenital heart defects (atrioventricular canal defect is common in trisomy 21) -Echocardiogram

Genetic counseling:

-Counseling provided to women who would like to conceive and their partners regarding genetic disorders, associated risk factors, and genetic testing.

Foods to avoid with PKU:

-Dairy products, eggs, meat and poultry, fish, nuts, beans, and foods that contain aspartame

Chromosomal abnormalities:

-Do not follow a straightforward pattern of inheritance. -Most chromosomal abnormalities occur due to an error in the sperm or egg, often during the process of cell division, leaving the sperm or egg with too few or too many chromosomes. -Abnormalities can occur in the number or structure of autosomal chromosomes or in sex chromosomes.

Nontraditional inheritance disorders:

-Do not follow the typical patterns of dominant, recessive, X-linked, or multifactorial disorders. -One type, mitochondrial disorders, is usually passed from the mother to the offspring because mitochondrial genes are inherited almost exclusively from the mother. -With nontraditional inheritance disorders, abnormalities are often seen in one or more organs, such as the brain, skeletal muscle, or eyes. -These disorders have a variable age of onset, from infancy to adulthood, and can have extreme variability in symptoms even within a family.

Congenital heart disease occurs more frequently in children with:

-Down syndrome

Most infants with the condition do not survive past the:

-First month of life, and complications are common for those who do survive longer.

Etiology and Pathophysiology:

-Follows an X-linked dominant inheritance pattern. -Fragile X syndrome has some unique features of inheritance. -For instance, unaffected males who carry the gene in premutation form may not have any symptoms themselves. -A protein called FMRP is responsible for regulating the production of other proteins and plays a role in developing synapses. -A gene called FMR1 provides instructions for making this protein, and mutations in this gene are the cause of fragile X syndrome. -In individuals with a full mutation, the FMR1 gene "shuts down".

Etiology and Pathophysiology:

-Follows an autosomal recessive inheritance pattern. -PKU results from a deficiency of a liver enzyme, leading to the inability of the body to process the essential amino acid phenylalanine. -Elevated levels of phenylalanine in the bloodstream can result in irreversible brain damage unless PKU is detected and treated.

GI defects:

-GI abnormalities of the intestines, esophagus, trachea, anus -Can cause GI blockage, gastroesophageal reflux, celiac disease -Ultrasound to assess for GI malformations

Prevent and manage complications:

-Have an increased risk of health complications such as cardiac, gastrointestinal, respiratory, immune, or musculoskeletal problems. -Update to dental, immunizations, well-child visits. -Hearing and vision problems are common in many genetic disorders. -Wear braces or orthotics for musckoskeletal disorders. -Wash hands to reduce the risk for infection

Individuals with Down syndrome can have a variety of complications:

-Heart defects -Gastrointestinal anomalies -Immune disorders -Obesity -Dental issues -Hearing and vision problems.

Complications include:

-Heart defects -Abnormalities of other organs

Endocrine problems:

-Hypothyroidism -Thyroid hormone level

Etiology and Pathophysiology:

-Individuals with Turner syndrome have either monosomy X, with only one copy of the X chromosome -Or X chromosome mosaicism, with chromosomal change in only some of their cells

Clinical Presentation:

-Intrauterine growth retardation and a low birth weight -Small, abnormally shaped head -A small jaw and mouth -Low-set ears -Short eyelid fissures -Clenched, overlapping digits -Prominent occiput -Severe hypotonia -Hypoplasia of the fingernails -Narrow hips with limited abduction -Short sternum

Trisomy 18, also called Edwards syndrome:

-Is a chromosomal condition that, in most cases, is not inherited. -Occurs in about 1 in 5,000 live-born infants, with the prevalence increasing with maternal age

Trisomy 21, also called Down syndrome:

-Is a chromosomal condition that, in most cases, is not inherited. -Occurs in about 1 in 700 newborns (~6,000 babies are born with the condition in the United States each year) -With the prevalence increasing with maternal age

Genetic disorders:

-Is a disease caused by an abnormality in an individual's genetic material.

Trisomy 13, also called Patau syndrome:

-Is a noninherited chromosomal condition. -Trisomy 13 occurs in about 1 in 16,000 newborns, with the prevalence increasing with maternal age.

Phenylketonuria (PKU):

-Is a rare, inherited, metabolic disorder. -It is an inborn error of metabolism and is detected during the first few days of life by newborn screening -Approximately 10,000 to 15,000 babies are born with PKU yearly. -This disorder affects males and females equally and occurs in all ethnic groups. -Although it is more common in individuals who are Native American or Northern European.

A special diet may be necessary for some genetic disorders; for example, a child with Down syndrome is more likely to:

-Is more likely to have celiac disease or other gastrointestinal disorders.

Clincal presentation:

-Is usually subtle during childhood, with minor dysmorphic features and developmental delay. -In adolescence, boys may present with features such as a large head, long face, and prominent ears, chin, and forehead, as well as flexible joints, flat feet, and enlarged testicles. -Children may present with a range of cognitive deficits, such as trouble with learning, solving problems, and speaking, as well as behavioral problems, such as biting, hand flapping, short attention span, and trouble making eye contact.

Children with Turner syndrome are more prone to:

-Kidney -Thyroid complications -Skeletal disorders

Before birth:

-Large fluid collection on the back of the neck or other abnormal fluid collections (edema) -Heart abnormalities -Abnormal kidneys

Assessment and diagnosis:

-Many times, the first signs include problems with sensation and people touching them, being anxious around crowds and in new situations, and behavior problems. -A delay in meeting developmental milestones may be the first assessment finding. -Diagnosis is confirmed with genetic testing.

Promote nutrition:

-May have trouble swallowing, sucking, or feeding because of a lack of muscle tone or lack of coordination of reflexes needed to suck and swallow. -Some may have an abnormally developed oral cavity, which can lead to feeding difficulties. -Some children with genetic disorders may need a gastrostomy tube or jejunostomy tube to be safely fed and achieve an adequate caloric intake.

Genetic disorders can be categorized into (4):

-Monogenic (Mendelian) -Multifactorial -Nontraditional inheritance -Chromosomal disorders:

Clinical Presentation:

-Most individuals with trisomy 21 have mild-to-moderate cognitive impairment with developmental delays and short- and long-term memory effects - Not all individuals with trisomy 21 have the same features. -Some common characteristics include: -Facial features, such as a flattened bridge of the nose and almond-shaped eyes that slant up -Cardiac defects, hearing and vision impairment, and increased mobility of the cervical spine

Inborn errors of metabolism: (Define)

-Mutations (or alterations) in the genes that direct our cells on how to make the enzymes and cofactors necessary for metabolism -such as phenylketonuria (PKU), require a special diet.

Assessment and Diagnosis:

-Newborn screening for PKU is required for all infants in the United States, and testing is completed 24 to 48 hours after protein feeding. -The infant needs to ingest enough formula or breast milk to raise the phenylalanine levels for the screening test to identify PKU accurately. -This is completed with a heel stick in the hospital -If the screening results aren't normal, a diagnostic test is required to determine whether the infant has PKU.

Therapeutic interventions:

-Nursing management should focus on developmental therapies such as those for children with intellectual disabilities.

Therapeutic Interventions:

-Nursing management should focus on health issues that arise because of the condition. -Medical concerns can include chronic middle ear infections, hearing loss, autoimmune disorders, and heart, liver, and kidney abnormalities. -Individuals with Turner syndrome may also experience difficulty with nonverbal communication skills, spatial relationships, and executive functions. -The primary treatments required for almost all girls and women with Turner syndrome include growth hormone and estrogen therapy.

Therapeutic interventions:

-Nursing management should focus on meal plans low in phenylalanine (low protein). -Formulas that are low in phenylalanine are available, and infants can have some breast milk. -Testing for phenylamine levels is part of the lifetime treatment of an individual with PKU. -As an infant, testing may need to be done once a week or more often. -Through childhood, testing may be done once or twice a month

Assessment and Diagnosis:

-Observation for the characteristic anomalies. -Prenatal testing or screening for the condition is available, and thus it can be diagnosed prenatally. -If not diagnosed prenatally, it is usually diagnosed in the first few days of life depending on the physical anomalies. -Trisomy 13 involves multiple abnormalities, many of which are life-threatening.

Assessment and Diagnosis:

-Observation for the characteristic anomalies. Prenatal testing or screening is available for the condition, and thus it can be diagnosed prenatally. -If not diagnosed prenatally, it is usually diagnosed in the first few days of life based on the physical anomalies. Trisomy 18 involves multiple abnormalities, many that are life-threatening. -Most infants with the condition do not survive past the first month of life, and complications are common for those who do survive longer. - Five to ten percent live past the first year but often have a severe intellectual disability.

Monogenic disorders:

-Occur when a single gene is defective. -Monogenic disorders may be autosomal dominant -Autosomal recessive -X-linked dominant -X-linked recessive.

Boys vs girls (Fragile X)

-Occurs in approximately 1 in 4,000 boys and 1 in 6,000 to 8,000 girls. -With boys experiencing more severe symptoms due to having only one X chromosome.

Promote growth and development:

-Often at risk for delayed growth and development related to cognitive deficits, physical disabilities, and activity restrictions secondary to their genetic disorder. -Screening for developmental capabilities to determine a child's current level of functioning is important. -Regular monitoring of height and weight is essential to identify growth patterns and deviations from growth trends. -Encourage parents to participate in early intervention programs available for their children. -Offer children age-appropriate toys and activities to encourage development. -Praise the child.

Therapeutic Interventions:

-Owing to the poor prognosis, nursing management should focus on symptomatic care for the infant and supportive care for the family.

Early intervention services may include:

-Physical therapy, occupational therapy, speech therapy, and special education.

Chromosome structure abnormalities occur when a:

-Portion of one or more chromosomes breaks and, during repair, the chromosomes are rejoined incorrectly, leading to too much or too little genetic material. -Parts of chromosomes can be missing (deletions) or have extra segments or components (duplications).

Assessment and Diagnosis:

-Prenatal screening tests can indicate the chances of a baby having trisomy 21. -They often include a blood test and an ultrasound, conducted to assess for fluid behind the baby's neck. -Diagnostic tests, including chorionic villus sampling, amniocentesis, and percutaneous umbilical blood sampling, are used after a screening test to confirm a diagnosis of trisomy 21. -If not diagnosed prenatally, trisomy 21 is usually diagnosed within the first few days of life depending on the physical characteristics associated with the syndrome. -Upon assessment, the infant may have poor muscle tone and loose joints, with a floppy appearance. -Developmental screening is also important for the child with trisomy 21.

Etiology and Pathophysiology:

-Results from random events that occur during the formation of eggs and sperm causing an error in cell division, leading to an abnormal number of chromosomes—in this case, three copies of the chromosome 13 in each cell. -Trisomy 13 can also occur with two normal copies of chromosome 13 and one extra copy of chromosome 13 attached to another chromosome in the cells.

Etiology and Pathophysiology:

-Results from random events that occur during the formation of eggs and sperm causing an error in cell division, leading to an abnormal number of chromosomes—in this case, three copies of the chromosome 18 in each cell. -Trisomy 18 can also occur with two normal copies of chromosome 18 and one extra copy of chromosome 18 attached to another chromosome in the cells. -Partial trisomy 18 can be inherited and involves an unaffected person carrying a rearrangement of genetic material between chromosome 18 and another chromosome. -Such a person does not have signs of trisomy 18 but is at an increased risk of having children with the syndrome.

Etiology and Pathophysiology:

-Results from random events that occur during the formation of reproductive cells (usually the egg cells) causing an error in cell division, leading to an abnormal number of chromosomes—in this case, three copies of the chromosome 21 in each cell. -The most common genetic chromosomal disorder and cause of intellectual disabilities in children. -The degree of intellectual disability and the degree of developmental delays vary in severity depending on the person.

Newborn screening:

-Routine screening performed on every infant born in the United States shortly after birth using heel-stick blood spots to detect a variety of congenital conditions.

Caregivers receive genetic counseling. Discharge Planning and Teaching:

-SOFT is a support organization for families who have a child with a chromosome abnormality.

Discharge Planning and Teaching:

-SOFT is a support organization for families who have a child with a chromosome abnormality.

Clinical manifestations of down syndrome:

-Short stature •Small head •Flat occiput •Flat face, including a flat nasal bridge and a small nose •Almond-shaped eyes, with an upward slant and epicanthal folds (small skin folds in the inner corners of the eyes) •Tiny white spots on the iris of the eye •Small, abnormally shaped, and low-set ears •A small mouth with an arched palate and a large, protruding tongue •A short neck, with abundant skin at the nape •Small hands with broad, short fingers; pinky fingers tend to curve toward the thumb •A single deep crease on the palm of each hand (palmar crease) •Congenital heart defect •Small feet, with excessive space between the large toe and the second toe •Lack of muscle tone •Excessively flexible and loose joints

Clinical Presentation:

-Signs and symptoms vary among girls and women with Turner syndrome. -Signs may first appear before birth, at birth, during infancy, or later in childhood, the teens, or in adulthood.

Childhood, teens, and adulthood:

-Slowed growth -No growth spurts at expected times in childhood -Adult height significantly less than might be expected for a female member of the family -Failure to begin sexual changes expected during puberty -Sexual development that "stalls" during teenage years -Early end to menstrual cycles not due to pregnancy -For most women with Turner syndrome, inability to conceive a child without fertility treatment

Sleep apnea:

-Soft-tissue and skeletal changes, leading to obstruction of the airway -Sleep apnea test, polysomnogram

Example, Children with Down syndrome:

-Tend to have small mouths and a flat, smooth, large tongue, in addition to lack of muscle tone. -These characteristics lead to difficulty sucking, swallowing, and feeding. -Adaptive devices, such as special nipples and eating utensils, are often used. -Special positioning, such as supporting the head, chin, and throat when feeding, is often necessary.

Evaluation:

-The average lifespan of an individual with trisomy 21 is approximately 60 years, and the prognosis has dramatically improved over the past few decades.

Outcomes:

-The child complies with a diet low in phenylalanine. -The child complies with phenylalanine level testing. -Phenylamine levels remain in the therapeutic range. -The child receives referrals for appropriate developmental therapies as needed. -Caregivers receive education and support for managing the condition.

Expected outcomes for a child with Turner syndrome include the following:

-The child is monitored closely for growth and development. -The child receives referrals for appropriate developmental therapies. -The child sees specialists as needed for health concerns that arise due to the syndrome. -Caregivers receive education and support for managing the condition.

Expected outcomes for a child with trisomy 13 include the following:

-The child receives comfort care. -The child receives symptomatic care as needed. -Caregivers receive supportive care. -Caregivers receive genetic counseling.

Expected outcomes for a child with trisomy 18 include the following:

-The child receives comfort care. -The child receives symptomatic care as needed. -Caregivers receive supportive care. -Caregivers receive genetic counseling.

Outcomes:

-The child receives routine vision and hearing tests. -The child receives regular medical care. -The child receives referrals for appropriate developmental therapies. -Caregivers receive education and support for managing the condition. -The child and caregivers receive supportive measures. -The child's growth and development are promoted. -The child is free of complications. -The child receives sufficient nutrition.

Expected outcomes for a child with fragile X syndrome include the following:

-The child remains free from injury to self. -The child receives referrals for appropriate developmental therapies. -Caregivers receive education and support for managing the condition.

Therapeutic Interventions:

-The prognosis for children with trisomy 21 has been improving in recent decades, and nursing management should focus on supportive care and preventing complications. -Refer children to these services, which include speech, occupational, and physical therapy, early on.

Evaluation:

-The prognosis is generally poor for children with trisomy 13.

In trisomies:

-There are three copies of a chromosome instead of the usual two.

Examples of abnormalities in the chromosome number include:

-Trisomy 21 (Down syndrome) -Trisomy 18 (Edwards syndrome) -Trisomy 13 (Patau syndrome)

Assessment and Diagnosis:

-Turner syndrome may be suspected prenatally if fetal edema on the back of the neck, heart abnormalities, or abnormal kidneys are seen on ultrasound. -If not suspected prenatally, the first indication is usually short stature and/or slow growth during infancy or childhood. -Diagnosis is confirmed using genetic testing.

Clinical Presentation:

-Usually, there are no symptoms at birth. -If PKU is undetected and untreated, infants can soon begin to show signs. -Initial signs and symptoms may include irritability, vomiting of protein feedings, musty body smell, increased reflex action, and seizures. -If left untreated or with dietary noncompliance, symptoms may include skin rashes, microcephaly, developmental delays, intellectual disabilities, and behavior problems such as hyperactivity

Foods you can eat with PKU:

-Vegetables, fruits, some grains, and other foods that are low in phenylalanine.

Turners syndrome:

-Which affects only females, is a chromosomal condition caused by the complete or partial absence of the second sex chromosome in some or all of the cells of the body. -It occurs in approximately one out of every 2,000 to 4,000 female live births. -Although it is much more common in pregnancies that do not survive to term.

At birth or during infancy:

-Wide or weblike neck -Low-set ears -Broad chest with widely spaced nipples -High, narrow roof of the mouth (palate) -Arms that turn outward at the elbows -Fingernails and toenails that are narrow and turned upward -Swelling of the hands and feet, especially at birth -Slightly smaller than average height at birth -Slowed growth -Cardiac defects -Low hairline at the back of the head -Receding or small lower jaw -Short fingers and toes