ATI Engage: Genetics and Genomics in Pediatric Nursing

what are genes?

a unit of heredity passed down from parent to child and used to determine some trait of the offspring

what is a genome?

the complete set of genes for a person

what are congenital anomalies?

irregularities that can affect the structure or function of the body and occur during pregnancy

what are some congenital anomalies?

-spina bifida

-tetralogy of fallot

-trisomy 21

what are chromosomal anomalies?

disorders that have irregularities in the shape or number of a single chromosome or multiple chromosomes

what can chromosomal anomalies result from?

an error when cells are dividing, during preimplantation, during pregnancy, or after birth

what is numerical anomaly?

this occurs when a chromosome pair is either missing one of the chromosomes or has more than the normal two

what is aneuploidy?

an imbalanced chromosomal complement caused by one or more extra or missing chromosomes

what is monosomy?

the absence of one chromosome from a pair of chromosomes

what is trisomy?

a syndrome in which there is an extra copy of a chromosome in the cell nucleus, resulting in developmental problems

what are autosomes?

any 22 of the 23 pairs of human chromosomes that do not determine male or female sex

what is a karyotype?

a complete set of chromosomes of an individual, arranged from smallest to largest

what is a homolog?

a pair of chromosomes that separates from each other during meiotic division

what is meiosis?

cell division in which the number of chromosomes is decreased in the sex cells (egg or sperm)

what is chromosome deletion?

part of the chromosome is missing or deleted

what is chromosome duplication?

part of the chromosome is duplicated

what is chromosome translocation?

part of one chromosome is moved to another chromosome

what is robertsonian?

the whole chromosome has attached to another one at the centromere

what is chromosome reciprocal?

portions from two different chromosomes have been switched

what is chromosome inversion?

part of the chromosome is broken off, inverted, and reconnected

what is a ring chromosome anomaly?

part of the chromosome is broken off and created a circle

what is cell free fetal DNA?

fetal DNA that is found in the pregnant parent's blood

what is karyotyping?

placing all 23 pairs of chromosomes from a person in order from smallest to largest after taking a picture of them

what is fluorescence in situ hybridization (FISH) test?

a molecular cytogenetic that offers the ability to localize a specific area on a gene or chromosome

what is chromosome microarray analysis?

a genetic test that can look for extra or missing chromosomes

what is the etiology of trisomy 21?

an error occurs, called nondisjunction, and a pair of 21st chromosomes do not separate in the egg or sperm cell before or at conception

what is nondisjunction?

this occurs when homologous chromosomes do not separate during cell division

what is the etiology of multifactorial heart disease?

-chromosomal changes

-environmental exposure

-mother's health (maternal diet, medications, and any contact with cigarette smoking)

which cardiac disease are most commonly found in females?

-atrial septal defect

-VSD

-PDA

what cardiac disease is most commonly found in males

CoA (although turner syndrome most commonly occurs in females)

what do children who have trisomy 21 have a higher risk of having?

-atrial septal defect

-VSD

what are some risk factors for PDA?

-family history of heart disorders

-birth at an elevation above 8,200 ft

- down syndrome

- viral illness (Rubella; German measles)

what are some risk factors for TOF?

-maternal age greater than 40 years

-family history of TOF

- down syndrome

- exposure rubella

what do children who have trisomy 21 or were exposed to viral illnesses, such as rubella in utero have a higher risk of having?

-PDA

-TOF

which cardiac conditions may a murmur be heard in a newborn?

-atrial septal defect

-VSD

-PDA

-CoA

how may a baby with TOF skin appear?

skin may have a bluish tint upon examination or become cyanotic when feeding or crying

for a baby who has CoA, which pulse may be weaker compared to the brachial and carotid pulses?

femoral

what are copy number variants (CNV)?

a circumstance in which sections of the genome are repeated, and the number of copies of a specific DNA segment vary between individuals

what are clinical manifestations for a child who has a complete atrial septal defect?

-pulmonary congestion

-right-sided heart failure

if a child has a small VSD, what are the clinical manifestations?

typically asymptomatic?

if a child has a medium VSD, what are clinical manifestations?

mild heart failure in late childhood

if a child has a large VSD, what are clinical manifestations?

-present with a murmur and congestive heart failure in early childhood, possibly even at birth if the defect is large enough

-poor weight gain

-tiring with feeding

what are clinical manifestations of PDA?

-murmurs

-hypotension in very low birth weight newborns

-respiratory distress

-low partial pressure of oxygen (PO2)

-tachycardia

-prominent precordial impulses

-bounding peripheral pulses

what is partial pressure of oxygen (PO2)?

the pressure of oxygen in a mixture of gases

what are precordial impulses?

visible or palpable pulse present on the anterior chest wall that comes from the heart or larger blood vessels

what are clinical manifestations of TOF?

-periods of cyanosis

-tet spells in which they become hypercyanotic (when the baby feeds or cries)

what are tet spells?

a condition in babies who have tetralogy of fallot in which the baby becomes blue gray or cyanotic with feeding and crying

what are clinical manifestations of CoA?

-hypertension in the upper extremities, causing bounding upper extremity pulses (brachial pulse in newborns)

-weak femoral and pedal pulses

-history of problems with feedings

-heart murmurs

-circulatory collapse resulting in shock

what is tuberous sclerosis?

a rare genetic disorder in which noncancerous tumors grow in different areas throughout the body

what is diabetes mellitus type 1?

an autoimmune disorder, occurs when a person's immune system cells do not recognize the beta cells in the pancreas and destroy them

what is the etiology of diabetes mellitus type 1?

-more than 60 areas on a chromosome that are passed down in families who have type 1 diabetes

-viruses

-maternal diet

-environmental influences on the mother and fetus

what are the risk factors of diabetes mellitus type 1?

-males

-parent or sibling has type 1 diabetes (highest risk identical twins)

-autoantibodies, specifically beta cell and anti-insulin antibodies

what are autoantibodies?

antibodies that react to a client's self-cells and cause an immune response

what diagnostic tests are used to confirm diabetes mellitus type 1?

-a1c

-random blood sugar

-fasting blood sugar

how is a type 1 diabetes diagnosis made?

the following occurs on two separate tests:

-a1C reading of greater than or equal to 6.5%

-random blood sugar greater than or equal to 200 mg/dL

-two fasting blood sugar tests greater than or equal to 126 mg/dL

what are clinical manifestations of diabetes mellitus type 1?

-unintentional weight loss

-polyuria

-polydipsia

-fatigue

-change in mental status

-vomiting

-dehydration

some children may present with manifestations of ketoacidosis, including:

-kussmaul breathing

-abdominal discomfort

-ketone smell (fruity breath)

-decreased level of consciousness

when does an autosomal dominant disorder occur?

when at least one dominant allele (A) is inherited from a parent

what is an allele?

different or alternate form of a gene

what are some autosomal dominant disorders?

-marfan syndrome

-huntington disease (HD)

-neurofibromatosis

-achondroplasia

what is marfan syndrome?

an autosomal dominant disorder pattern that affects connective tissue in the body

what is the etiology of marfan syndrome?

-faulty fibrillin (elastic fibers in connective tissue) caused by a FBN1 gene mutation on chromosome 15, which leads to malfunctioning fibrillin

-non-inherited de novo mutation (25% of cases)

what is de novo mutation?

a genetic mutation that was not inherited from either parent

what are risk factors of marfan syndrome?

-having a parent who carries the dominant allele, with a child having a 50% chance of developing MFS from that parent

-both male and females affected equally

what testing is done to diagnose marfan syndrome?

-check the heart for aortic root dilation

-evaluate the skeletal system since the client who has MFS can have pectus deformities and scoliosis

-perform a slit-lamp examination to evaluate the ocular lens for signs of dislocation

-genetic testing to search for a mutation in the FBN1 gene

what are clinical manifestations of marfan syndrome?

-arachnodactyly

-scoliosis

-chest deformities (pectus excavatum or pectus carinatum)

-tall and thin with flat feet

-deep set eyes

-nearsightedness

-retinal detachment

-dislocated lens

-glaucoma and cataracts

-aortic dissection, dilation, and rupture

-aortic regurgitation

-mitral valve prolapse

what is arachnodactyly?

condition in which a client has long and slender fingers that look like spiders

what is pectus excavatum?

a chest wall deformity in which the breastbone sinks in and looks concave

what is pectus carinatum?

also called pigeon breast, it is a chest wall deformity in which the ribs and breastbone push out

what is huntington disease?

an autosomal dominant and rare neurodegenerative condition

what is the etiology of hutington disease?

-repetition of cytosine, adenine, and guanine (CAG) bases on chromosome 4p16.3 in the Huntington (HTT) gene

what are the risk factors of hutington disease?

-a parent has the disease (50% chance)

-instability of CAG and the length of CAG repeats in the HTT gene

what testing can be done to diagnose hutington disease?

-chorionic villus sampling (CVS) or amniocentesis to discover if the fetus has inherited HD

-neurological exam along with a complete history and physical

-brain imaging, such as a CT scan or MRI

-genetic testing (36 or more repeats, the client is considered positive for HD; if there are 26 or less, then HD is ruled out)

when do clinical manifestations of hutington disease begin?

-between 30 and 50 years of age; however, if they start before 20 years of age, it is known as juvenile huntington disease

-will occur earlier in the client if they have more CAG repeats

what are clinical manifestations of hutington disease?

=poor attention span, irritability, and loss of impulse control, and as the disease progresses, apathy, depression, and psychosis can occur

-difficulty with executive functions and progression to dementia

-spasmodic involuntary movements (chorea), difficulty with activities of daily living, and difficulty with ambulation

what is the median survival of hutington disease?

15 to 18 years after the first clinical manifestations are noted

what is neurofibromatosis?

a neurocutaneous, autosomal dominant disorder consisting of nervous system and benign skin tumors and has two types: neurofibromatosis type 1 (most common) and neurofibromatosis type 2

what is the etiology of neurofibromatosis?

-type 1: results from a mutation that leads to loss of function on the neurofibromin 1 (NF1) gene, which is located on chromosome 17

-type 2: results from a mutation that leads to loss of function on the neurofibromin 2 (NF2) gene, which is on chromosome 22

what is the risk factor of neurofibromatosis?

having a parent affected with the gene (50% chance)

when is neurofibromatosis 1 diagnosed?

early infancy when clinical manifestations appear but is diagnosed more commonly as the child grows, most often by 10 years of age

when is neurofibromatosis 2 diagnosed?

not diagnosed until late adolescence or early adulthood, when the clinical manifestations are first noticed

what testing can be done to diagnose neurofibromatosis?

-observing certain clinical manifestations

-genetic testing is not ordered unless a child presents with café-au-lait macules without a family history of these macules

how is a client diagnosed with neurofibromatosis?

client must meet at least two of the seven following criteria:

-Café-au-lait macules (six or more) that are greater than 5 mm (before puberty) or greater than 15 mm (after puberty)

-neurofibromas affecting the skin (two or more) or plexiform neurofibromas (one or more)

-freckling in the armpits or groin area

-optic glioma (tumor of the optic nerve)

-lisch nodules (two or more)

-bone deformities of the eye socket or long bone

-immediate family member, such as a parent, sibling, or child who has neurofibromatosis type 1​​​​​​​

what are neurofibromas?

benign tumors that grow on nerves

what are plexiform neurofibromas?

a type of benign tumor that can grow along nerves

what are lisch nodules?

dome-shaped, yellow-brown elevations on the surface of the iris in the eye

what are schwannomas?

a type of nerve sheath tumor

what are meningiomas?

central nervous system tumors that emerge from the meninges

what are clinical manifestations of neurofibromatosis 2?

-hearing loss

-tinnitus

-problems with balance

-most commonly present with meningiomas and schwannomas

what is achondroplasia?

an autosomal dominant disorder that affects the skeletal system, resulting in a shorter stature between 42 and 56 inches

what is the etiology of achondroplasia?

-mutation on a portion of the fibroblast growth factor receptor 3 (FGFR3) on chromosome 4

-20% of cases, achondroplasia occurs in children who have at least one parent with the mutation, whereas the other 80% occur from a de novo mutation

what are risk factors for achondroplasia?

-if both parents carry the mutation, the child has a 50% chance of inheriting one mutated gene (heterozygous), a 25% chance of not inheriting either mutation, or a 25% chance of inheriting mutated genes from both parents (homozygous)

-if the child has the homozygous type, they usually die in the early neonatal stage

-paternal age of 35 and older increases the risk of the child having a de novo mutation

when is achondroplasia diagnosed?

prenatally or after birth during a routine history and physical exam

what are clinical manifestations of achondroplasia?

-short stature

-enlarged head with a frontal bossing with small nasal bridge

-crowded or crooked teeth

-brachydactyly

-genu varum

-lordosis

-kyphosis

-trident hand

-foramen magnum stenosis, which causes compression of the spinal cord

-hearing impairment secondary to frequent acute otitis media -chronic otitis media with effusion of the middle ear -neurological impairment related to stenosis of the lumber spine

what is brachydactyly?

condition in which toes and fingers are shorter than average

what is genu varum?

a condition in which the legs of the child bow outwards (bow legged)

what is a trident hand?

a noticeable gap between the middle and ring fingers

how do autosomal recessive inheritance patterns occur?

a diseased allele must be inherited from each parent (may skip generations)

if both parents are carriers and have children, what are the odds of the child inheriting an autosomal recessive inheritance?

-25% chance the child will inherit the disorder, a 25% chance the child will not be affected, and a 50% chance the child will be a carrier of the diseased allele

-greatest risk of passing on the disorder occurs when there is consanguinity, or a blood relationship between two related individuals

what are some autosomal recessive disorders?

-cystic fibrosis

-tay-sachs

-beta thalassemia

-sickle cell disease

-congenital adrenal hyperplasia

what is the etiology of cystic fibrosis?

the result of a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene on chromosome 7