Genetic Syndromes Flashcards
Cystic Fiberosis
Etiology and Demographics
Pathophys.
Etiology
- autosomal recessive disorder of multiple organ systems: especially pancreas and lung function
- if a CF carrier: asymptomatic; thus birth of a child with CF is the first sign usually that there is genetic ties to CF
Demographics
- 1 in 3600 births : most common lethal inheritable disease in the white population
Pathophys.
- CF gene is located on long arm of chromosome 7 : here it codes for amino acid glycoprotien CFTR: which alters the structure and function of a wide range of organ involvement
CFTR: cystic fiberosis transmembrane conductase regulator: this gene then goes to impact
- lungs (big one)
- pancreas
- upper respiratory
- sweat glands
- intestines
- liver
- reproductive tract
results essentially in thickening of mucus and secretions and the inability to clear them
CF
clinical manifestations: how is it tested for in the Newborn Screen
Newborn Screen: includes testing for CF
- universally accepted as part of the screen aka everyone test for this
Test: 2 tier testing
1: a serum immunoreactive trypsinogen (IRT) level
- if this is + = then they go on to test with tier #2
- thise can result in a false negative if there is a meconium ileus (aka stool blocks last part of ileum: this is common in CF kids, but can register as negative)
2: second teir test: a second IRT test OR a genetic mutation test
- if the second test comes postive: confirmatory testing is down with a sweat chloride test
CF: Clinical Manifestation
Infections
where
what bugs
Infections
- pt. have an ineffective mucociliary clearance ability and this predisposes them to increased infections: specifically of the airaway
Bugs: pseudomonas, s. aureus and H. flu
- pseudomonas: leads to biofilm growth (scarring, inflammation, decrease lung function) and leads to an overall decline in pulmonary function
CF: Clinical Manifestation
lower respiratory tract infections
how the infection = destroys lungs & cycle
what this leads to
lower respiratory infections
- ongoing neutrophil inflammation = results in DNA released from the dying neutrophils
- this DNA release from dead cells = leads to an increased in the mucus and viscosity of the airway secretions
- CF pt. have decreased ciliary function: thus the thick secretion + inability to clear = stasis and distal airway plugging
Result = early on in lungs, there is structural changes and increased IL-8 mediators
this can happen despite the child looking and presenting “healthy” but leads to decreased lung function over time
thus, decreased lung function = increased infections = a constatnt cycle of infection & inflammation = puntate exacerbations = bronchiectasis (damange!!)
increased risk for complications
- hemoptysis
- PTX
death = due to respiratory failure, cor pumonale due tot eh recurrent infections
CF: Clinical Manifestation
Upper Respiratory Infections
pathology and what is commongly seen
Pathology
- the same as lower RI: there is a cycle of infection, inflammation, muscus thickening, decreased clearnace, increased fiberosis and scarring = changes teh lungs = bronchiectasis
Symptoms
- predisposes them to chronic and recurrent sinusitis of atypical bacteria
- sinuse hypoplasia
- nasal polyps (not allergy related) are seen & cause obstruction = leading to sinusitis
CF: Clinical Manifestation
Pancreas Involvment
pathology and symptoms
Patology
- the CFTR gener within the pancrease: leads to blockage of teh ducts and destruction of the pancreatic acini
- blockage + destruction = pancreatic insufficency
- usually exocring fucntion > endocrine function effected (thus decreased absorbtion)
SYmptoms
- decreased absorbtion: carbohydrate, protines, fat soluable vitamins
- difficult to gain weight
maintaining nutrtion status for these pt. is importatn to maintain pulmonary function
CF: Clinical Manifestation
Pancreas involvement: CF Diabetes
due to the pancreatic destruction of the acini cells = CF related diabetes (CFRD)
- a relative insulin deficiency from the islet cell destruction
Screening: should begin at age 10 and be annual
Symptoms
- majority: asymptomatic
- poor growth
- inreased freqency of pulmonary exacerbations and unexpected decline in pulmonary function
these pt. rarely develop DKA: but are at the same risks for microvascualr and neurologic complications
Treatment
- insulin
- do NOT put them on a diabetic diet: this will compromise their nutrtional status
CF: Clinical Manifestation
GI involvmenet
meconium ileus
GI invovlemen in older kids/adults
GI Involvement
Meconium Ileus: an obstruction in the fetuses distal ileus due to the increases thickened meconium in the CF pt.
- results in a delayed passing of the meconium
complications as a reuslt
- volvus
- intestinaol atresia
- meconium peritonitis
Older Kids/Adults
- poor hydration of intestinal contents
- thickened intestinal secretions
- fecal stasis
- all the above lead to intestinal obstrcutions
these regions of stasis and obstruction = can lead to intussusception: telescoping of bowel onto itsef
these can also lead to rectal prolapse due to difficult to pass stool
CF: Clinical Manifestation
Liver
Liver Involvement
- rare, but can lead to death
- focal biliary cirrhosis: due to dehydration and increased viscosity of the bile
- portal hypertension develops due to this and death
CF: Clinical Manifestation
Bodily Fluids
Bodily Fluids:
- overall lose their electrolytes of sweats: results in metabolic alkalosis
- sodium, chloride and potassium lost in sweat: can be exacerbated with acute illness or vomiting
CF: Clinical Manifestation
Skeletal changes
Skeletal
- osteopenia and osteoporisis due to a variety of reasons
- failure to thrive
- delayed puberty
- liver disease
- malabsrbtion of calcium, mag., vit D and K
- steroid use: on these due to exacerbation
transient arthritis seen in CF pt.
CF: Clinical Manifestation
Puberty/Fertility
FC: delayed puberty seen in both males and females
Causes
- poor nutrtion
- decreased glucose tolerance
- delay in the rise of sex hormones
Male Infertility
- due to reduced testosterone and epidydimal size
- bilateral absecne of vas deferens
- in mild CF cases: the subfertility may be the fisrt manifestation
CF: Physical Exam Findings
vitals
growth patterns
head and Neck exam
Vitals
- respiratory rate and HR should be monitored and compared to the age related norms
- O2 status checked at every visit
Growth PArameters
- concerns arise when CF pt. fails to gain weight or height
- concerns arise when CF pt. cross percentiles (decreased)
Head and Neck : assess for signs of URI and sinusitis
- check ears for otitis media: freqeunt OM with aminoglycoside treatmern: need to assess audiometery
- nasal mucosa: assess for polyps
- palapte sinus
CF: Physical Exam Findings
Chest and Lungs
Chest & Lungs
- child able to talk without coughing or getting dyspneic
- accessory muscle use
- auscultation : may here the following
- adventicioius sounds may not be clear, or only clears for a short period of time
- disease progresses = decreased breath sounds and tubular
- unilateral sounds = think PTX (can be subtle as the lung sounds are already diminished)
Heart
- with progression of lung disease = development cor pulmonale
- fixed splitting of first and second heart sound
- increased loudness of the second heart sound
CF: Physical Exam Findings
abdomen
Gu
extremities
Abdomen
- look for acute intestinal obstruction
GU
- sexual maturity rating should be assessed
Extremities
- joints: exam for swelling and CF related arthropathy
- digits and nails: look for clubbing (decrease O2)
- assess for edema from low protein
