ATI Genetics and Genomics in Pediatric Nursing

genetics

the study of individual genes and how they are inherited between generations

precision medicine

An individual's genetic makeup along with lifestyle/environment contributes to disease prevention and treatment

genomics

the study of the human genome

congenital anomalies

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

- ex. spina bifida, trisomy 21

chromosomal anomalies

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

- can result from an error when cells are dividing, during preimplantation, during pregnancy, or after birth

numerical chromosomal anomalies

- a difference in the number of chromosomes

- also known as a numerical anomaly or aneuploidy

- if a chromosome is missing: monosomy

- if extra chromosome is present: trisomy

autosomal aneuploidies

an unexpected number of chromosomes in the first 22 pairs

sex chromosome aneuploidies

an unexpected number of sex chromosomes

structural chromosomal anomalies

structure of chromosomes can be changed by deletions, duplications, translocations, inversions, or rings

deletions

part of the chromosome is missing or deleted

duplication

part of the chromosome is duplicated

translocation

part of one chromosome is moved to another chromosome

inversion

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

ring

part of the chromosome is broken off and forms a circle

genetic testing

- can be performed after obtaining samples from the mother prenatally via chorionic villus sampling, amniocentesis, or through a blood draw for cell-free fetal DNA

- after the cells are obtained via these methods, they will be analyzed by karyotyping, fluorescence in situ hybridization (FISH) test, chromosome microarray analysis, or DNA testing

trisomy 21

when a child has all or part of an additional chromosome 21

trisomy 21 etiology

nondisjunction occurs, keeping the 21st pair of chromosomes from separating before or at conception

trisomy 21 risk factors

- women over 35

- parents who have a chromosomal abnormality

trisomy 21 screening

- a blood test can assess alpha fetoprotein (AFP) levels in the blood, with a decreased level suggesting Down syndrome

- an ultrasound can look for anomalies in the fetus

chorionic villus sampling

- done in the first trimester

- looks at placental tissue

amniocentesis

- done in second trimester

- investigates amniotic fluid surrounding the fetus in the amniotic sac

percutaneous umbilical blood sampling

looks at umbilical cord blood

to confirm trisomy 21 diagnosis

karyotyping or FISH test

trisomy 21 physical manifestations

- short height

- small hands/fingers/feet

- small mouth

- low-set ears

- protruding tongue

- epicanthic folds (eyes that slant upward)

- flat nasal bridge/occiput

- transverse single crease palmar

trisomy 21 clinical manifestations

- heart: atrioventricular septal defects (AVSD) and ventricular septal defects (VSD)

- GI: imperforate anus, atresia, Hirschsprung disease, constipation, diarrhea, gastroesophageal reflux disease (GERD), and celiac disease

- hematologic: increased risk of leukemia

- neurologic: learning disabilities, hypotonia, joint hypermobility; these children have a higher risk for seizures and early-onset Alzheimer's disease

multifactorial heart diseases

atrial septal defect, ventricular septal defect (VSD), persistent/patent ductus arteriosus(PDA), coarctation of aorta (CoA), and Tetralogy of Fallot (TOF)

multifactorial heart disease etiology

the causes of heart disease can be unknown, but factors such as chromosomal changes, environmental exposure, mother's health, or a combination of all can play a part

PDA risk factors

- history of heart disorders

- born at elevation above 8,200 ft

- children with trisomy 21

- females

TOF risk factors

- mother greater than 40

- family history of TOF

multifactorial heart disease diagnosis

- diagnosed during pregnancy with fetal electrocardiogram

- after birth, echocardiogram can confirm diagnosis

atrial septic disease clinical manifestations

- pulmonary congestion

- right sided heart failure

- some children with partial ASD may be asymptomatic in their early years

ventricular septal defect clinical manifestations

- if defect is small, child is usually asymptomatic

- moderate defect may display signs of heart failure in early childhood

- major defect will present with a murmur and congestive heart failure in early childhood along with poor weight gain and tiring from feeding

persistant ductus arteriosus clinical manifestations

- murmurs

- hypotension in low birth weight newborns

- respiratory distress

- low PO2

- tachycardia

- bounding peripheral pulses

metrology of fallot (Toa) clinical manifestations

- cyanosis

- hyper cyanotic episodes when feeding or crying (Tet spells)

coarctation of aorta clinical manifestations

- hypertension in upper extremities, causing bounding upper extremity pulses

- weak femoral and pedal pulses

- heart murmurs

- circulatory collapse

- problems with feedings

autism spectrum disorder (ASD)

neurological disorder that affects a child's development and how the child interacts with their environment

ASD etiology

multifactorial due to environmental factors and variations in the hundreds of genes that are involved

ASD risk factors

- 4 times more common in males

- siblings with ASD

- birth complications

- mothers older than 35

ASD diagnosis

diagnosed by assessing development

ASD clinical manifestations

- present by age 2

- difficulty communicating/interacting

- delays in learning, language, and movement

spina bifida

neural tube defect that occurs during fetal development

spend bifida etiology

multifactorial including: folate deficiency, maternal diabetes and obesity, and medication use such as valproic acid.

spina bifida risk factors

- folate deficiency, maternal diabetes and obesity, and medication use such as valproic acid.

- advanced maternal age and maternal obesity or diabetes

spina bifida clinical manifestations

- no clinical manifestations

- may have dimple or tuft over affected area of spine

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

- inadequate supply of insulin and hyperglycemia.

DM etiology

- family history

- viruses, maternal diet, and environmentalinfluences on the mother and fetus

DM risk factors

- males

- presence of autoantibodies

DM diagnosis

blood test if child has history of weight loss, polyuria, and polydipsia

DM clinical manifestation

- weight loss

- polyuria

- polydipsia

- fatigue

- change in mental status

- vomiting

- dehydration

- ketoacidosis

- Kussmaul breathing

autosomal dominant inheritance patterns

- occur when at least one dominant allele is inherited from a parent

- only needs the one allele that carries the disorder to inherit it and show clinical manifestations of the disorder

Marfan syndrome

autosomal dominant disorder pattern that affects connective tissue in the body

Marfan etiology

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

MFS risk factors

parent who carries dominant allele

MFS clinical manifestations

- arachnodactyly, scoliosis, and chest deformities (pectus excavatum or pectus carinatum)

- tall and thin with flat feet.

- ocular: deep set eyes, nearsightedness, retinal detachment, dislocated lens, and glaucoma and cataracts

- cardiovascular: aortic dissection, dilation, and rupture; aortic regurgitation; and mitral valve prolapse.

Huntington disease

autosomal dominant and rare neurodegenerative condition

Huntington etiology

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

Huntington risk factors

if one of parents has disease

Huntington clinical manifestation

- typically begin age 30-50

- poor attention span, irritability, and loss of impulse control, apathy, depression, and psychosis

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

neurofibromatosis

- autosomal dominant disorder

- neurocutaneous, autosomal dominant disorder consisting of nervous system and benign skin tumors

neurofibromatosis risk factors

parent affected with the gene

neurofibromatosis clinical manifestations

- 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

Achondroplasia

- autosomal dominant disorder

- affects the skeletal system, resulting in a shorter stature between 42 and 56 inches

Achondroplasia risk factors

parent carries the mutation

Achondroplasia clinical manifestations

- short stature

- enlarged head with a frontal bossing with small nasal bridge - crowded or crooked teeth

- brachydactyly

- genu varum

- lordosis

- kyphosis

- trident hand

autosomal recessive inheritance patterns

- to occur, a diseased allele must be inherited from each parent. Because each parent must pass on the diseased allele, the disorder may skip generations, and often, an affected parent may have an unaffected child

- males and females affected equally

cystic fibrosis

autosomal recessive disorder that affects exocrine gland function

CF risk factors

two parents who carry the gene

CF clinical manifestations

- mucus secretions that are thickened and block affected organs, such as the lungs, pancreas, intestines, sinuses, liver, cervix, vaginal vault, and vas deferens

- lungs are affected when mucus plugs block the bronchioles, and the lungs become obstructed

- mucus then becomes a breeding ground for bacteria, and subsequent infections can occur, which can lead to inflammation of airways

Tay Sachs disease

autosomal recessive disorder that progressively damages brain and spinal cord neurons

Tay Sachs risk factors

receives allele from both parents

Tay Sachs clinical manifestations

- begins 3-6 months of age

- mild muscle weakness

- exaggerated startle reflex

- sensory hyperstimulation

- cherry-red spot on the retina

- can progress to seizures, increased muscular weakness, macrocephaly, and decreased level of consciousness, resulting in death by 4 to 5 years of age

Beta Thalassemia

- autosomal recessive disorder affects hemoglobin levels in the blood

- classified as beta thalassemia major, intermedia, and minor

BT risk

inherits an allele from each parent

BT clinical manifestations

- mild anemia, such as dizziness or weakness, fatigue, pallor, or headaches

- thalassemia major, diagnosed by the age of 2, have more severe anemia, which presents as failure to thrive, developmental delays, irritability, abdominal distension, diarrhea, pallor, jaundice, recurrent fevers, hepatosplenomegaly, and bone deformities

Sickle cell disease

autosomal recessive disorder that affects many systems within the body

SCD risk factors

inherit damaged hemoglobin S gene from each parent

SCD clinical manifestations

- begin at 6 months of age

- dactylitis and pain

- infantile stages: facial grimacing, restlessness, irritability, fussiness, excessive crying, refusing to feed, or change in sleep patterns.

- beyond infant stage: vaso-occlusive crisis; acute chest syndrome; anemia; osteonecrosis; blood clots or stroke; fever or infection; kidney complications, such as chronic kidney disease; proliferative retinopathy; pulmonary hypertension; and organ damage

Congenital Adrenal hyperplasia

autosomal recessive disorder that affects the production of corticosteroids, mineralocorticoids (aldosterone), and male sex hormones (androgens)

CAH risk

when both parents pass allele to child

CAH clinical manifestations

- androgen deficiency: female infants will present with ambiguous genitalia caused by virilization, early and excessive growth of body hair

- androgen deficiency: male infants will present with penile enlargement and hyperpigmentation, early and excessive growth of body hair

- aldosterone deficiency: dehydration, hypovolemia, and very low blood pressure

X linked recessive disorders

- typically occur in males only. Because males only have one X chromosome, a damaged or mutated gene would guarantee the recessive trait is inherited

- For a female child to have manifestations of the disorder, they would need to inherit one damaged gene from the carrier mother and the other from the affected father

Duchenne muscular dystrophy

X-linked recessive disorder that leads to weakness and progressive deterioration of muscle fibers.

DMD risk factors

male

DMD clinical manifestations

- begin ages 2-3

- weakness, and problems with ambulation, such as difficulty running and climbing stairs, may be observed, and the incidence of falls may increase due to weakness

- pseudo trophy in calves and toes

- cognitive impairment

- hypotonia and poor head control

Turner syndrome

when one X chromosome is deleted or missing in the female client

Turner risk factors

none

Turner clinical manifestations

- lymphedema of the hands and feet

- neck webbing

- small nails that curve upward

- high-arched palate

- hands with short fourth metacarpals

- short stature

- Madelung's deformity

- delayed puberty

- cubitus valgus

- learning diabilities/attention deficit

- renal anomalies such as horseshoe or malrotated kidneys

- cardiovascular anomalies

- liver disorders

- hypertension

- autoimmune disorders

genomic imprinting

occurs when a child inherits genes from a parent in which the genes are only active in that maternal or paternal gene

uniparental disomy

when a child inherits both versions of chromosomes from one parent and none from the other

Prader Willi syndrome

strong neurobehavioral component with stages of nutritional responses affected by both metabolic and endocrine systems. ​​​​​​​

PWS etiology

occurs when there is a paternal deletion on chromosome 15 in the Prader-Willi critical region

PWS risk

none

PWS major clinical indicators

- hyperphagia

- narrow forehead with downturned mouth

- small genitalia, with delayed puberty and infertility

- developmental delays

PWS minor clinical indicators

decreased movement in infancy

- sleep issues

- behavioral problems

- shorter stature than other family members

- light hair, skin, and eye color

- narrow and small hands along with small feet

- poor pronunciation

- nearsightedness

- skin picking

- thick saliva

PWS clinical manifestations

- poor sucking reflex, which leads to feeding difficulties and failure to thrive

- almond-shaped eyes

- narrow nose bridge

- thin upper lip

- downturned mouth

- dolichocephaly

- hyperphagia

- rapid weight gain

Angelman syndrome

rare genetically inherited form of mental retardation due to the deletion or inactivation of specific genes on the maternally inherited chromosome 15

Angolan syndrome risk

none

AS clinical manifestations

- begin at 6 months of age

- ataxia

- impaired speech

- microcephaly

- seizures

- short attention span

- interrupted sleep patterns

- protruding tongue

- feeding problems as an infant

- wide mouth, wide-spaced teeth

- strabismus

- prognathism

- hypopigmentation

- scoliosis

inborn errors of metabolism

- there is a problem with the enzyme and it does not work as it should, there can be a problem with protein or carbohydrate metabolism, glucose storage, and fatty acid breakdown

- most of these disorders are autosomal recessive

Phenylketonuria

a genetic disorder in which the essential digestive enzyme phenylalanine hydroxylase is missing