FNU NP704 Module 10: PEDS: Genetic probs (CF/sickle/downs), CA, DM, JIA, Purpura/ITP

CF: Other S/Sx

Barrel Chest/Clubbing Fingers -Scoliosis or Kyphosis Delayed growth and development -Aquagenic wrinkling of palms (AWP) Elevated blood sugar Electrolyte Imbalance related to copious sweating Intestinal obstruction caused by meconium plug in newborns (10% of patients) Eosinophilia Alkalemia Hyponatremia Allergic bronchopulmonary aspergillosis (hypersensitivity reaction to Aspergillus in the CF airways, causing inflammation, obstruction, aggravates CF lung disease. Tx - systemic corticosteroids (prednisone) and antifungal agents (itraconazole).

Anomaly-specific Referrals/testing

Brain, kidney anomalies- US Skeletal dysplasias- radiologic imaging Genetic testing referral- chromosomal abnormalities Cardiology referral for heart murmurs- ekg, echo Neurology referral for neurologic abnormalities or spinal defects- MRI, craniosynostosis -CT

Types of leukemia

CML chronic myelogenous leukemia ALL acute lymphoblastic leukemia

Acute Sickle Cell Crisis: Labs

Check vital signs, CBC, comprehensive metabolic panel, reticulocyte count, and oxygenation saturation (in adults).

Genetics: Teratogens

Chemical, physical, biologic agent effects during fetal development Maternal infections/disease- Rubella, CMV, toxoplasmosis, herpes, varicella, DM phenylketonuria, Fetal Alcohol Syndrome, Radiation

The primary goals of CF treatment

- Maintaining lung function as near to normal as possible by controlling respiratory infection and clearing airways of mucus - Administering nutritional therapy (ie, enzyme supplements, multivitamin and mineral supplements) to maintain adequate growth - Managing complications

Cystic Fibrosis: causes

A defect in the CFTR gene causes cystic fibrosis (CF). This gene makes a protein that controls the movement of salt and water in and out of your body's cells. In people who have CF, the gene makes a protein that doesn't work well. This causes thick, sticky mucus and very salty sweat. *Infants failing to thrive suspect CF (EEP) Every person inherits two CFTR genes—one from each parent. Children who inherit a faulty CFTR gene from each parent will have CF. Children who inherit one faulty CFTR gene and one normal CFTR gene are "CF carriers." CF carriers usually have no symptoms of CF and live normal lives. However, they can pass the faulty CFTR gene to their children. * If each parent has a normal CFTR gene and a faulty CFTR gene, each child has a 25 percent chance of inheriting two normal genes; a 50 percent chance of inheriting one normal gene and one faulty gene; and a 25 percent chance of inheriting two faulty genes.

Lymphoma: tests

A chest x-ray assesses for a mediastinal mass. The diagnosis ultimately requires a pathologic confirmation from tissue or fluid sampling.

Down's Syndrome: screening

A-fetoprotein (AFP)- a protein secreted during the fetal life by the liver, GI tract, and yolk sac. High AFP is associated with NTDs and the disruption of fetal integument . Low AFP is associated with fetal aneuploidy (Down's syndrome, trisomy 13, trisomy 18). quad screen- unconjugated estriol, inhibin A, human chorionic gonadotropin (HCG), and AFP. Done in 2nd trimester. If risk is high or if there is familial history, US or serum screening abnormalities or concerns → chorionic villus sampling (CVS) or amniocentesis is offered. Small risk of complications or pregnancy loss. Screening sonogram @18weeks gestation- anatomy scan for congenital anomalies of brain, heart, kidneys, lungs, and spine.

When does acute lymphoblastic leukemia peak?

Acute lymphoblastic leukemia peaks during early childhood (ages 2 to 5 years).

CF: Genetics

Affects gene Cystic Fibrosis Transmembrane Conductance Regulator, CFTR) codes for a molecule that forms a channel for chloride ions and thus regulates the amount of fluid in the mucous membranes. Most mutations lead to complete absence of the channel. More than 1800 mutations have been described. · The gene for CF is located on the long arm of chromosome 7, encodes for a polypeptide, the cystic fibrosis transmembrane regulator (CFTR), a chloride channel located on the apical surface of epithelial cells. · CFTR is important for the proper movement of salt and water across cell membranes and maintaining the appropriate composition of various secretions, especially in the airways, liver, and pancreas. · Secretory and absorptive characteristics of epithelial cells affected by abnormal CFTR, result in the clinical manifestation of CF.

Lymphoma s/sx

EBV plays a causal role in both types. Rarely seen in children younger than 5 yrs old & incidence increases w/age. M>F The most common for Hodgkin disease: painless, firm lymphadenopathy, one or two lymph node areas; usually supraclavicular & cervical nodes. Mediastinal lymphadenopathy producing cough or shortness of breath - frequent initial presentation. The presence of one of three B symptoms has prognostic value: fever (>38° C for 3 consecutive days), drenching night sweats, and unintentional weight loss of 10% or more within 6 months of diagnosis. Mediastinal mass can cause life threatening airway obstruction. May affect renal function - uric acid crystals. Clinical manifestations: Lymphadenopathy, anemia, bleeding, neutropenia.

CF: Surgical Management

Surgical therapy may be required for the treatment of the following respiratory complications: · Pneumothorax · Massive recurrent or persistent hemoptysis · Nasal polyps · Persistent and chronic sinusitis GI tract complications requiring surgical therapy are as follows: · Meconium ileus Some managed with contrast (Gastrografin) enemas · Intussusception · Gastrostomy tube placement for supplemental feeding · Rectal prolapse Lung transplantation is indicated for the treatment of end-stage lung disease. Studies suggest that, although lung transplantation may improve quality of life, it may not lengthen survival

CF: Pulmonary Problems

Tachypnea - Respiratory Distress Crackles/wheezes - Cough dry or productive Cyanosis Neck masses Hoarseness Minor Hemoptysis - Airway Infection Major Hemoptysis - Bronchial arterial bleeding (chronic infection) Chest pain Chronic sinusitis - Nasal Polyposis Pneumothorax - Advanced lung disease

Pain management in hospitalized patient with SCD

hospitalized patients with an acute painful sickle cell episode have a pain assessment, clinical assessment, and appropriate analgesia within 30 minutes of presentation. Once treatment is administered, pain relief should be assessed every 30 minutes until satisfactory relief has been achieved, and then at least every 4 hours.

Genetics: Multifactorial

polygenetic inheritance (genetic/environment), occurring 1st/2nd degree relative M>F Hypertrophic Pyloric Stenosis, NTD (spina bifida/anencephaly)

How to manage a vaso-occlusive crisis

severe pain use opioid medications. less severe use NSAID Hospitalize patients for vaso-occlusive pain that is uncontrolled with oral medications, as well as for chest pain, shortness of breath, or hypoxia to exclude the possibility of acute chest syndrome. Hospitalize for an acute drop in hemoglobin. Evaluate acute abdominal pain urgently.

Interdisciplinary Team Intervention: Speech-Language

speech and language therapist part of overall educational program and based on the tested language strengths and weaknesses of child. Hearing intervention done by audiologist or otolaryngologist.

The sweat chloride test

the standard diagnostic test for this disorder. o It is positive (elevated sweat chloride >60 mEq/L) in 99% of patients with CF. · DNA tests detect many CF mutations, but because there are so many (over 1, 500, and other not identified), DNA will not detect all cases of CF. · Newborn screening is based on either elevated immunoreactive trypsinogen (IRT) levels or DNA tests, but because these both have false-positive, false-negative results the diagnostic test of choice is the SWEAT TEST

Genetics: Autosomal Dominant

trait every generation, 50/50 chance, M=F risk, usually regulatory/structural mutation Achondroplasia, Neurofibromatosis, Marfan

Genetics: X-linked

early in female development one X is inactivated,they are carrier, have some manifestations, males > affect

CF: Routine Treatments

**Patients are to be monitored in the CF clinic every 2-3 months** Mild acute pulmonary exacerbations of cystic fibrosis can be treated successfully at home with the following measures: · Increasing the frequency of airway clearance · Inhaled bronchodilator treatment (especially if bronchial hyperresponsiveness is present or as part of airway clearance [inhaled bronchodilator followed by chest physiotherapy and postural drainage]) · Chest physiotherapy (airway secretion clearance technique) · Postural drainage · Aerosolized DNAse and 7% hypertonic saline by nebulizer, decreases the viscosity of mucus · Increasing the dose of the mucolytic agent dornase alfa (Pulmozyme) · Monitor pulmonary bacterial flora via airway cultures · With exacerbations: pts often require 2-3 week courses of high dose IV antibiotics and aggressive chest physiotherapy · Antibiotics are chosen based on sputum culture, or possibly throat culture

Supportive care for CF

1. pancreatic enzymes - aid in digestion due to malfunctioning pancreas 2. chest physiotherapy 3. nebulizer treatments 4. frequent antibiotics for recurrent infection

Specific inherited conditions: H&P

A thorough history, family history, prenatal history and genetic history. Take a good look at the parents. ie: Does the child have the same low-set ears as dad? A thorough review of systems - what have the parents noticed? Work on getting specific, detailed answers about the baby's symptoms and behavior pattern. Do a complete head to toe physical exam, noting any dysmorphology, including things like muscle tone and what they feel like.

Genetic anomalies: H&P

A thorough history, including family history, prenatal history and genetic history if known. Then take a good look at the parents. Does the child have the same low-set ears as dad?A thorough review of systems - what have the parents noticed? Work on getting specific, detailed answers about the baby's symptoms and behavior pattern. Then do a complete head to toe physical exam, noting any dysmorphology, including things like muscle tone and what they feel like. One of my kids had a "doughy" feel, not firm flesh like you would expect on a young infant. Your textbook reviews some of the more common abnormalities you may find.

Medications used to treat patients with cystic fibrosis may include:

Antibiotic therapy - helps control chronic infection (eg, oral fluoroquinolones) · Pancreatic enzyme supplements (contain lipase and proteases) Stool loss of fat and protein may still be high even with supplements Dose should be titrated to optimize fat absorption (not to exceed 2500 U/kg/meal) Exceeding this dose is associated with fibrosing colonopathy · Multivitamins (including fat-soluble vitamins, A, D, E, K) · Mucolytics · Nebulized, inhaled, oral, or intravenous antibiotics · Bronchodilators · Anti-inflammatory agents · Agents to treat associated conditions or complications (eg, insulin, bisphosphonates) · Agents devised to potentially reverse the abnormalities in chloride transport (eg, ivacaftor, lumacaftor/ivacaftor) · The Pulmonary Therapies Committee of Cystic Fibrosis Foundation recommends long-term use of hypertonic saline for patients with cystic fibrosis aged 6 years or older to improve lung function and to reduce the number of exacerbations. · Oral laxatives (polyethylene glycol) - Distal intestinal obstruction syndrome (DIOS) · Bile salt ursodeoxycholic acid - cholestasis

CF: Respiratory sx

Chronic or recurrent cough is usually the first symptom. Acute pneumonias are most commonly caused by Staphylococcus aureus, Haemophilus influenzae and Pseudomonas aeruginosa. The lungs are chronically colonized by the microbes, which leads to gradual destruction of the lung tissue. Chronic sinusitis is common, and 10-30% of the patients develop nasal polyps.

What cranial nerve deficits may show involvement of the brainstem?

Cranial nerve deficits other than sixth nerve palsy suggest involvement of the brainstem.

Interdisciplinary Team Intervention: Medical, PC and all subspecialties

Curative treatment not always possible, functional impairment can be minimized. Palliative care, hospice, bereavement may be necessary for children with limited life expectancy.

Cystic fibrosis

Cystic fibrosis (CF) is a hereditary metabolic disease. Its main symptoms include progressive pulmonary symptoms in the childhood and exocrine insufficiency of the pancreas, which leads to chronic steatorrhoea. Diagnosis is based on the measurement of chloride concentration in the sweat. The test can be supplemented with the investigation of gene mutations

Interdisciplinary Team Intervention

Educational-home based infant stimulation → special services (extra attention, special education classroom). Psychological- child directed or family oriented → advice giving, counseling, psychotherapy, behavioral management techniques, psychopharmacologic methods. Motor - PT or OT. Neurodevelopmental therapy (NDT)- hierarchical and plastic nervous system development. Sensory integration therapy- OT structure sensory experience from tactile, proprioceptive, and vestibular systems Speech-Language- speech and language therapist part of overall educational program and based on the tested language strengths and weaknesses of child. Hearing intervention done by audiologist or otolaryngologist. Social and Environmental- include nursing or social work involvement for the family. Case managers may be necessary. Medical- PC + all subspecialties. Curative treatment not always possible, functional impairment can be minimized. Palliative care, hospice, bereavement may be necessary for children with limited life expectancy.

Which tumors peak during the first two years of life?

Embryonal tumors, such as neuroblastoma and retinoblastoma, peak during the first 2 years of life.

What other benign conditions or viruses may mimic CA?

Epstein-Barr virus, cytomegalovirus, and mycobacterial infections can cause fever, lymphadenopathy, organomegaly, weight loss, and abnormal blood counts. Juvenile idiopathic arthritis and other collagen vascular disease can cause musculoskeletal pain and anemia, mimicking leukemia.

Specific inherited conditions: labwork and imaging

Potential lab work includes the newborn screening done in every state. In addition chromosomal analysis can rule in/rule out some disorders. Imaging is based on abnormal findings on physical exam or to look for specific defects that you know are common with certain syndromes.

X-linked Dominant Inheritance

Females and males affected, affected mothers can have females < severe symptoms or not affected, boys not affected, can be lethal in males Vitamin D resistant rickets- males, females Incontinentia pigmenti- lethal in males they die in utero. Rett Syndrome- females often dx with autism

S/S of Leukemia:

Fever, pallor, petechiae or ecchymoses, lethargy, malaise, anorexia, and bone or joint pain. Physical examination - lymphadenopathy and hepatosplenomegaly. Most pts have abnormal CBC - anemia & thrombocytopenia common. WBCs can be low, normal or high. Clinical manifestations: Arthritis, extremity pain, lymphadenopathy, anemia, bleeding, hypercalcemia. May effect renal function - uric acid crystals. Lumbar puncture - should always be performed to evaluate the possibility of CNS involvement. A chest x-ray should be obtained in all patients to exclude an anterior mediastinal mass, which is commonly seen in T-cell ALL. Electrolytes, calcium, phosphorus, uric acid, and renal and hepatic function should be monitored in all patients.

CF: Gastrointestinal Problems

Failure to Thrive - Steatorrhea Stinky Stools -Meconium Ileus Rectal Prolapse - Dry Skin (Vit A deficiency) Cheilosis (Vit B deficiency) Diarrhea Constipation Polyuria Distal intestinal obstruction syndrome (DIOS) Hepatosplenomegaly Fatty Liver and/or portal HTN

The diagnosis for CF should be seriously considered in any infant presenting with:

Failure to thrive · CF should be in the differential diagnosis of children with chronic respiratory and gastrointestinal symptoms, especially if there is digital clubbing. · Any children with nasal polyps, especially in younger than 12 years, should be evaluated for CF · All sibling of patients with CF should also be evaluated. If a child was not screened for some reason, or was born before 2010, you may be the first to suspect CF. o If so, order a sweat chloride test and then send to a pediatric pulmonologist.

Patients with an acute pain episode (SCD)

For patients presenting with an acute pain episode, the (NICE) recommends monitoring for abnormal respiratory signs or symptoms, chest pain, fever, and hypoxia. Other complications that can be seen with patients in acute crisis include stroke, aplastic crisis, infection, osteomyelitis and splenic sequestration.

Signs of a slow-growing tumor

Irritability, anorexia, poor school performance, and loss of developmental milestones.

CF in neonates and infants

Jaundice due to obstructive hepatitis, Edema due to protein deficiency, Anemia as well as disorders due to deficiency of fat soluble vitamins Bleeding tendency: Vitamin K Hemolytic anemia: Vitamin E Increased intracranial pressure: vitamin A

X-linked Recessive Inheritance

female carrier, 50/50 chance of boys inheriting trait, and girls being a carrier Color blindness, Duchenne MD, Hemophilia A

What are the most common childhood cancers?

Hematopoietic tumors (leukemia, lymphoma) are the most common childhood cancers, followed by brain/central nervous system (CNS) tumors and sarcomas of soft tissue and bone.

Explain the patho and genetic inheritance of SC disease vs SC trait

Hemoglobin S forms polymers when deoxygenated. The polymers form rigid fibers that align and distort the red blood cell. Sickled red blood cells lead to micro- and macro-vaso-occlusion. Vaso-occlusion causes intermittent ischemic episodes that lead to tissue damage and necrosis. Chronic hemolytic anemia and recurrent vaso-occlusive episodes lead to acute and chronic end-organ damage. The primary sx is pain (acute and daily chronic pain) Chronic physical findings may include stunted growth and development, jaundice, hyposplenia, or lack of a spleen. HA in pt with SCD may be a sign of stroke Priapism is a common complication in males with SCD and needs emergent attention SCD is an autosomal recessive inherited disease SCD disease is when 2 genes for sickle cell are inherited and therefore is expressed and has SCD SC trait is when 1 gene for sickle cell is inherited but no symptoms. The 1 gene can then be passed on to offspring

CF: Diet and Exercise

High-energy and high-fat diet (High Calorie diet), in addition to supplemental vitamins (especially fat soluble) and minerals, is recommended to compensate for malabsorption and the increased energy demand of chronic inflammation Nutritional supplements in the form of either high-energy oral preparations (eg, Scandishake) or enteral feeds (eg, elemental formulas, high-fat mixtures) via nasogastric tube or gastrostomy may be indicated in some patients. In one study, gastrostomy tube placement has been shown to significantly improve percentile body mass index and percent-predicted FEV1 in male patients and female pediatric patients. Regular exercise increases physical fitness in patients with cystic fibrosis. Upper body exercises, such as canoe paddling, may increase respiratory muscle endurance.

Acute Sickle Cell Crisis: Management

If chronic pain exists, refer for outpatient management of chronic pain. If severe anemia is present, admit and evaluate for aplastic crisis. If patient has chest pain, shortness of breath, or hypoxemia: urgent evaluation for acute chest syndrome. If abdominal pain is present: evaluate for splenic or liver sequestration or gallbladder disease. Treat pain with oral medications: NSAIDS and or opioids and adjuvant pain medications. Reassess hourly. If pain remains uncontrolled after several treatments; admit and treat with IV medications. Consult hematology if suspicion exists for a sickle cell complication. Treat with IV fluids and incentive spirometer. Evaluate pain regularly. Check CXR and daily CBC. If pain is controlled and vital signs are stable: discharge to home and continue treatment as an outpatient with close follow-up. Once admitted, treat with IV opioids using patient-controlled anesthesia when possible. Begin to convert to oral opioids within 24 to 48 hours unless there is clinical evidence of failure to tolerate oral medications. Convert to oral opioids using equianalgesic dosing principles. Observe for additional 24 hours once on oral medication before discharge. Taper opioid medications as outpatient. Follow closely after discharge.

CF common presentations:

In general, CF causes thick sticky mucus in secretions. 10% of newborns will present with meconium ileus, because the meconium is so thick they cannot pass it. Older children (not diagnosed as infants) commonly present with pulmonary manifestations such as poorly controlled asthma and chronic respiratory infections. The pancreas gets clogged with thick mucus, leading to a deficiency of pancreatic enzymes - so kids don't digest very well, especially fats and proteins, leading to vitamin deficiencies and steatorrhea from poor fat absorption. Protein and fat malabsorption (failure to thrive, hypoalbuminemia, steatorrhea), liver disease (cholestatic jaundice), or chronic respiratory infection are common. Mucus plugging in the lungs causes bronchiectasis and recurrent infection.

CF and reproductive systems

Inspissation of mucus in the reproductive tract leads to reproductive dysfunction in males and females. In 98% of men, the lack of (lack Vas deferens and azoospermia) seminiferous tubules leads to aspermia, but spermatogenesis is normal thus making the aspiration of sperm cells directly from the testicles possible. In females, secondary amenorrhea is often present as a result of chronic illness and reduced body weight. Abnormal secretions of the fallopian tubes and cervix are also common but men and women are still able to conceive children.

Patient education regarding SCD?

Instruct patients to avoid extremes of temperature, which can initiate a crisis, to dress appropriately when outside, and to avoid swimming in cold water.

What are common PE findings in leukemia?

Lymphadenopathy and organomegaly

CA s/sx

Many s/s are nonspecific. Although most children with fever, fatigue, weight loss, or limp do not have cancer, each of these symptoms may be a manifestation of an underlying malignancy. Uncommonly a child with cancer will have no symptoms at all. An abdominal mass may be palpated on routine examination, or a complete blood count (CBC) may be unexpectedly abnormal. The most common manifestations: fatigue, anorexia, malaise, pain, fever, abnormal lump or mass, pallor, bruising, petechiae, bleeding, headache, vomiting, visual changes, weight loss, and night sweats. Lymphadenopathy and organomegaly are common in leukemia. Solid tumors (palpable, measurable mass)- malignant masses are firm, fixed, and nontender; masses that are infectious or inflammatory are softer, mobile, and tender to palpation. Other s/s limp, cough, dyspnea, cranial nerve palsies, and papilledema. Keep in mind, some viruses & benign conditions can mimic s/s of cancer: Epstein-Barr virus, cytomegalovirus, and mycobacterial infections can cause fever, lymphadenopathy, organomegaly, weight loss, and abnormal blood counts. Juvenile idiopathic arthritis and other collagen vascular disease can cause musculoskeletal pain and anemia, mimicking leukemia.

non-Hodgkin lymphoma vs hodgkin lymphoma

Memory trick: that Hoe is contagious! (HOdgkin's= contagious lymph node spreading).

Unusual Patterns of Inheritance

Mitochondrial inheritance- randomly distributed when fertilized eggs divide Uniparental Disomy- inherited 2 copies of one parents chromosome and none from the other parent Prader-Willi, Angelman Syndrome Trinucleotide Repeat Fragile X Syndrome, Huntington's dx, Myotonic dystrophy, Friedreich and spinocerebellar ataxia

S/S of CNS Tumors

Need complete neuro assessment, including visual fields and a funduscopic examination. Symptoms of increased ICP: lethargy, headache, and vomiting esp in am on awakening. 6th cranial nerve palsy is a common sign of increased ICP. Signs of slow growing tumor: Irritability, anorexia, poor school performance, and loss of developmental milestones. In young children with open cranial sutures, an increase in head circumference may occur. Optic pathway tumors - loss of visual acuity or visual field defects. Inability to abduct the eye, Cranial nerve deficits other than sixth nerve palsy suggest involvement of the brainstem. Seizures 20% to 50%; focal weakness or sensory changes. Pituitary involvement produces neuroendocrine effects (galactorrhea with prolactinoma, excessive growth with growth hormone secretory tumors, precocious puberty). Cerebellar tumors are associated with ataxia and diminished coordination. MRI is exam of choice. Do not do LP before MRI as need to assess for increase ICP. May also need to do MRI of the spine if MRI of the head is positive. Clinical manifestations: abnormal head size, shape & fontanels, visual impairment & leukocoria, vomiting, & headaches.

Cystic fibrosis: S/sx

Of those born with CF, 90% have exocrine pancreatic insufficiency: Inspissation (thickening) of mucus and destruction of the pancreatic ducts results in the inability to excrete pancreatic enzymes into the intestine, leading to: Malabsorption of proteins, sugars, and FAT. Fat malabsorption manifests as steatorrhea (large, foul-smelling stools), deficiencies in fat-soluble vitamins (A, D, E, and K), and failure to thrive. (Insufficient energy intake leads to growth retardation) Protein malabsorption can present in infancy as hypoproteinemia and peripheral edema Of those born with CF, 10% have intestinal obstruction caused by inspissated meconium Meconium ileus Intestinal obstruction in older pts results from thick inspissated mucus in the intestinal lumen causing: Distal intestinal obstructive syndrome Rectal prolapse may in some rare cases be the sole presenting symptom. Copious sweating may lead to salt deficiency (hyponatremia) and to metabolic alkalosis from failure of the sweat glands to conserve sodium and chloride.

Which CAs peak in adolescence?

Osteosarcoma peaks during adolescence; and Hodgkin disease peaks during late adolescence.

From BBB: SCD notes

Our job to be medical home and recognize medical crisis. •Difference between SC disease vs SC trait: Difference between trait and disease: trait is carrier state- unlikely to have symptoms, but in certain circumstances- mountain climbing/excessive strain- may have sx, unpressurized airplane. SCD: horrible, we don't manage. Identified on PKU test at birth if not ID prenatally. •S/S of sickle crisis: What is most commonly affected- smaller blood vessels: kidney, heart, lung, and brain.Warning signs: fever, pain, s/sx of stroke- may have sudden change in behavior or performance level, may not be the same as in adult. Get to hospital. Pain management. •FNP role in care •Fluids, pain management: we do use narcotics with these kids in crisis, anything less doesn't help them. Risk of abuse or addiction, but you have to consider quality of life. •REFER! •Medical home

Interdisciplinary Team Intervention: Motor

PT or OT. Neurodevelopmental therapy (NDT)- hierarchical and plastic nervous system development. Sensory integration therapy- OT structure sensory experience from tactile, proprioceptive, and vestibular systems

CF and the pancreas

Pancreatic islets are gradually destroyed by the pancreatic enzymes, and the incidence of diabetes increases by age (adolescents and adults). Insulin deficiency (initially presents as glucose intolerance, but true diabetes that requires insulin therapy (CF-related diabetes) may develop. One fourth of the patients develop diabetes after the age of 25 years.

Lymphoma: Labs

Patients suspected needs CBC, ESR, CMP, calcium, phosphorus, lactate dehydrogenase, and uric acid.

Genetic anomalies: Patient approach

Pedigree determine autosomal dominant, AR, x-linked, or sporadic disorder Question couple's age pregnancy info - maternal hx, maternal chronic or acute conditions, medications, infection. f/u with amniocentesis or CVS

Genetic anomalies: Lab work and imaging

Potential lab work includes the newborn screening done in every state. In addition chromosomal analysis can rule in/rule out some disorders. Imaging is based on abnormal findings on physical exam or to look for specific defects that you know are common with certain syndromes.

Provide preventative and well care to children with SCD

Provide genetic counseling and screening Perform annual transcranial Doppler examinations for children with SCD, aged 2 to 16 years. Refer to an ophthalmologist for a dilated eye examination to evaluate for retinopathy beginning at age 10 years Treat children prophylactically with twice daily penicillin (125 mg for those aged <3 years and 250 mg for those aged ≥3 years) until age 5 years, unless they have had a splenectomy or invasive pneumococcal infection. Prophylactic penicillin significantly reduces the risk of pneumonia in children with SCD. Hydroxyurea is the only approved drug for treatment of SCD. Reduces frequency of pain crisis and hospitalization Instruct patients to avoid extremes of temperature, which can initiate a crisis, to dress appropriately when outside, and to avoid swimming in cold water.

When do we evaluate children with SCD for retinopathy?

Refer to an ophthalmologist for a dilated eye examination to evaluate for retinopathy beginning at age 10 years

CF: Patho

Respiratory disease is caused by decreased amount of mucus which leads to impaired ciliary function of the epithelial cells of the respiratory tract and thus weakens the natural resistance mechanism. The patients develop exceptionally strong inflammatory response towards incipient infections. 90 % of the exocrine secretory tissue of pancreas is destroyed in 85-90% of patients before birth by own proteolytic enzymes, which leads to gastrointestinal absorptive disorder. Excretory disturbance causes fatty liver disease in 70% of patients and aspermia in 98% of men. In females, fertility is impaired due to exceptionally viscid cervical mucus. · Abnormal airway secretions make the airway more prone to colonization with bacteria. · Defects in CFTR may also reduce the function of airway defenses, promoting bacterial adhesion in the airway epithelium. · This leads to chronic airway infections and eventually bronchial damage (bronchiectasis). Abnormal variation in the CTR that blocks transport of chloride ions across epithelial cells on mucosal surfaces Cell surface becomes inadequately hydrated, organs are damaged, and secretions become extremely viscous

Complications of Down's Syndrome

heart disease (need an echocardiogram and cardiac consult in the first few weeks of life, if it is not done shortly after birth) GI tract anomalies congenital hypothyroid polycythemia at birth leukemia infection cataracts alzheimer-like features (>35 y/o).

Describe care for children with sickle cell disease

Screen for conditions as recommended by the USPSTF for all patients along with specific sickle cell conditions, including stroke, retinopathy, pulmonary hypertension, kidney disease, liver disease, and osteoporosis Give PNA, influenza, meningococcal, and heb b vaccine Secondary screening is recommended for pulmonary HTN, kidney function, retinopathy, live assessment Drug therapy for pain includes NSAIDs, opioids, and adjuvant pain medications.

Down's syndrome: Screenings in PC

Screenings are up to us: hearing and vision(frequent defects): opthamologic at 6 months- and then depending on results, need scheduled appointments for reevaluation, hearing tested Q 3 years, cardiologist consult regularly, TSH screening starting at age 1 and continuing every couple of years. More susceptible to infection, GI problems, autoimmune problems. More common to have depression, but masked by communication difficulties- especially high-functioning DS kid, knows "different". Atlantoaxial instability with C-spine Xray if checking off on sports. Sports injuries more likely due to differences in muscle tone, may need supportive devices.

Genetic anomalies: adolescence

Some hereditary disorders are late in onset (huntington, blindness, spinal muscular atrophy). genetic consultation for mutation or carrier risk for offspring.

CF: BBB notes

The cause of CF is a chloride channel defect and a genetic defect. It is autosomal recessive, so sometimes you may have a family hx Sometimes you know because we've checked during pregnancy Most states are doing the CF screening with the PKU (newborn screening) test This is not the child that is likely to show up in your office undiagnosed, but could happen especially if someone had a home birth. The infant may present with a meconium ileus before you get the PKU result back because it causes thick, sticky meconium that that child just can't pass. They also get thick sticky mucus in lungs and in secretion in general Pancreas doesn't work well so they don't digest food well (especially fats and proteins) so they can have big bulky, fatty stools, have difficulty digesting things, and need to be on pancreatic enzymes Sticky mucus in lungs causes mucus plugging Symptoms can vary widely depending on how severe it is. Because so many gene can be associated with CF it can be mild or awful

CF: establishing a diagnosis

The presence of one or more typical clinical features of CF (chronic pulmonary disease, characteristic gastrointestinal and nutritional abnormalities, salt loss syndromes, or obstructive azoospermia) AND: 1. Two elevated sweat chloride tests performed at an accredited CF foundation certified laboratory (Positive = >60, Borderline = 40-60, Negative = <40) 2. Two mutations known to cause CF identified by DNA analysis or 3. A characteristic abnormality in ion transport across nasal epithelium demonstrated in vitro (nasal potential difference testing) o For those identified by a positive newborn screening or because a sibling has CF, sweat chloride testing or the presence of known disease-causing DNA mutations are the only criteria required for diagnosis, as clinical symptoms may not be manifested early in life.

What is lymphoma?

cancer of the lymph nodes- 2 types - Hodgkin disease and NHL non-Hodgkin lymphoma

What kind of prophylactic treatment do we give to patients with SCD and when?

Treat children prophylactically with twice daily penicillin (125 mg for those aged <3 years and 250 mg for those aged ≥3 years) until age 5 years, unless they have had a splenectomy or invasive pneumococcal infection. Prophylactic penicillin significantly reduces the risk of pneumonia in children with SCD. Hydroxyurea is the only approved drug for treatment of SCD. Reduces frequency of pain crisis and hospitalization

Genetics: chromosomal abnormalities:

Trisomies- congenital heart disease, GI anomalies, increase risk for leukemia Downs 21( 3pairs of chromosome 21),lab test recommended annually after 1 year of age as it's associated with multiple defects- CBC and TSH (EEP) Trisomy 18 usually SGA and 13 usually fatal 1st yr, Klinefelter Syndrome, Turner Syndrome, Cri Du Chat Syndrome, Williams Syndrome, Chromosome 22q 11.2 Deletion Syndrome, Inverted duplication chromosome 15, Cat Eye Syndrome

Down's Syndrome

Trisomy 21: normal birth weight but hypotonic characteristic facial appearance- brachycephaly, flattened occiput, hypoplastic midface, fattened nasal bridge upslanting palpebral fissures, epicanthal folds large protruding tongue.

Types of sickle cell crisis

Vas-occlusive -hydration -pain management -blood transfusion Splenic sequestration -Blood transfusion -supportive Aplastic -Blood transfusion -supportive Hemolytic -Blood transfusion -supportive

Interdisciplinary Team Intervention: Educational

home based infant stimulation → special services (extra attention, special education classroom).

CF: Our role

We order the sweat chloride test, and refer if positive. We provide supportive care and medical home · CF patients seen by pulmonology and possibly gastro if having a lot of GI complaints · Since pulmonologist are used to dealing with CF, since these kids used to die as children some pediatric pulmonologist have CF patients into adulthood due to the lack of knowledge of pulmonologists managing adults · Our job is also discussing contraceptives when they get to adolescence because we are the medical home · Often CF is diagnosed prior to birth, with the prenatal testing (amniocentesis or chorionic villus sampling) that many women have. (carriers are heterozygous) · Since 2010, all 50 states also do CF testing as part of the newborn screening. · All infants with a positive newborn screen and/or with meconium ileus should be evaluated for CF. · Often the family has a written plan from the pulmonologist to deal with infections and exacerbations that we can start, then refer back to the CF clinic for persistent or worsening illness

Warning signs for CF from BBB

What you guys really need to know is, Recognize this, Provide the supportive care, Recognize worrisome signs when they would need to go see the pulmonologist or go to the ER urgently. · If they show up with really severe chest or abdominal pain, if they have a high fever, if they have a major exacerbation from their base-line symptoms- they will always have a cough so if things are progressing then you need to pay attention. · Don't have them wait at home to see if the cough develops into something worse · Usually the pulmonologist will have an action plan for respiratory infections, so recognize that and get them into a higher level of care.

Testing considerations

When considering imaging, chromosomal analysis, refer child to a genetics clinic. They will evaluate based on patterns of anomalies and better to let specialists do a formal diagnostic process. BUT....it is reasonable for NP to start this process, in some cases the child is normal but may have odd features. Consider parents and putting them through a huge, expensive work-up for nothing. If satisfied that the child is growing and developing normally and in no danger, you can watch for a while.

What is leukemia?

a malignant progressive disease in which the bone marrow and other blood-forming organs produce increased numbers of immature or abnormal leukocytes. These suppress the production of normal blood cells, leading to anemia and other symptoms.

Genetic anomalies: IEP (Individualized Educational Plan)

addresses any deficiencies and determines individual needs (tutoring, behavioral classes). Collaboration between school and physician. Physician's goals- identify cause of dysfunction Refer to appropriate subspecialty → neuro, PT, psychological assessment, educational assessment, social assessment

Genetics: Autosomal recessive

both parents carriers 25/100 chance Sickle Cell, Tay Sachs

Hodgkin's lymphoma

cells in the lymphatic system grow abnormally and may spread beyond the lymphatic system. As Hodgkin's lymphoma progresses, it compromises your body's ability to fight infection. Hodgkin's lymphoma is one of two common types of cancers of the lymphatic system. The other type, non-Hodgkin's lymphoma, is far more common.

Interdisciplinary Team Intervention: psychological

child directed or family oriented → advice giving, counseling, psychotherapy, behavioral management techniques, psychopharmacologic methods.

Genetic anomalies: Maternal factors-

chronic conditions may expose fetus to maternal medications that may be teratogenic acute illnesses expose fetus to infectious agents that may cause birth defects other factors- maternal smoking, alcohol use, radiation, chemicals → consider genetic counseling.

Genetic anomalies: Postnatal considerations

consultation with geneticist for newborn or infant presence of malformation, abnormal results on routine screening test, abnormalities with growth (FTT, increase in length, abnormal head growth), developmental delays.

Genetic anomalies: interventions in primary care

determine if refer for further diagnostic workup and management or manage in PC. Non Judgemental, supportive, listener with climate of trust, allowing family to express difficult or painful thoughts and feelings. Educate parents

Interdisciplinary Team Intervention:Social and Environmental

include nursing or social work involvement for the family. Case managers may be necessary.

Preventative Care:

information regarding inheritance and risk for recurrence in subsequent pregnancies, instruct patients and parents regarding appropriate airway clearance technique and the need for chest physical therapy. Also, instruct patients and parents regarding the use of various drug delivery devices, such as valved holding chambers, and nebulizers, and the methods for modifying the pancreatic enzyme dosage. Be prepared to counsel families regarding the impact of the diagnosis on the emotional life of parents, siblings, and members of the extended family 2. See above section on management of acute pulmonary exacerbations, meds, diet and exercise - these too need patient/family education in order to prevent hospitalization

Signs of increasing ICP in CNS tumor

lethargy, headache, and vomiting esp in am on awakening. 6th cranial nerve palsy is a common sign of increased ICP.

Signs of an optic-pathway tumor

loss of visual acuity or visual field defects. Inability to abduct the eye,

Genetic anomalies: medical home

maintains close oversight of treatments and subspecialty services, provide preventative care, facilitate interactions with school and community agencies. sub-specialties include (but are not limited to): primary care, dental, behavioral, GYN, WIC, etc. family centered care- family and child to feel in control. treatments should promote greatest degree of normalcy for patient and family. As child matures, self-management programs provide health education, self-efficacy skills, and techniques such as symptom monitoring to help promote good long-term health habits. Introduce 6-7 y/o or when chores can be done. Limits helplessness, vulnerable child syndrome. provider should be aware of local facilities and programs for assessment and treatment. Under federal law, all children are entitled to assessment if there is a suspected developmental delay or a risk for delay.

CF: Epi

most common hereditary metabolic disease among most Caucasian populations; among them its incidence varies from 1 in 2,500 newborn infants (Great Britain) to 1 in 20,000 (Finland). · Cystic Fibrosis (CF) is the most common life-limiting genetic disorder seen in Caucasians · It is a chronic and progressive disease · Autosomal recessive disorder, with several mutations of the CF gene, leading to great variation in expression of the disease (More than 1500 mutations of the CFTR gene have been identified. The most common mutation is a deletion of three base pairs resulting in the absence of phenylalanine at the 508 position, F508).

Genetic assessment

referral patient (consultants) to geneticist (probands). families with relatives affected with genetic disorders consanguinity- in some cultures, relatives mate. Increases the chance that a child will be born with a rare autosomal recessive (AR) condition. The closer the relation, the greater the chance.

CF treatment overview

· Treatment is multifactorial, primarily directed towards the GI and pulmonary complications. · Supportive care - pancreatic enzymes, chest physiotherapy, nebulizer treatments, frequent antibiotics for recurrent infection, etc. · Care is complex, which is why a dedicated CF clinic is so important. Children used to die from CF at an early age. With improvement in treatment, they are living into their mid-30s and potentially beyond. · One of the issues that you may encounter with your adult CF patients is infertility (both male and female), again secondary to sticky mucus production that leads to mechanical obstruction. · Pancreatic enzyme adjustment, adequate hydration, and dietary fiber may help prevent recurrent episodes.

From BBB: Down's syndrome

•Caused by? trisomy 21- usually recognized at birth or before birth. •S/S -facial features, hypotonia, short broad hands, feeding difficulty, other associated features •Associated features: mental retardation, cardiac abnormalities, GI anomalies, hypothyroidism, atlantoaxial instability, autism, epilepsy, polycythemia, leukemoid reaction •Management: Down's specific growth curve, close follow up. Regular labs, coordination of care. See often, use different growth curve- heavier, smaller head, shorter stature. Diet and regular physical activity to prevent the associated obesity.