MULTISYSTEM & GENETIC DISORDERS

HUMAN IMMUNODEFICIENCY VIRUS (HIV): a pandemic caused by a retrovirus that erodes he human immune system over time,
resulting in immune incompetence and increases susceptibility to opportunistic infections and malignancies. Eventually HIV progresses
to AIDS ( CD4 is < 1,500)
ETIOLOGY SIGNS/SYMPTOMS MANAGEMENT
HIV belongs to genus Lentivirus of Retroviridae Fever, night sweats, weight loss, skin rashes, oral Highly active antiretroviral
family. ulcers, diarrhea, lymphadenopathy, wasting therapy (HAART) if indicated
HIV1→ global epidemic Genital STD’s, Shingles/recurrent herpes Discuss immunization &
HIV2→ less pathogenic, mostly in West Africa SOB on exertion, dry cough prophylaxis

ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS): an advanced stage of the human immunodeficiency & is diagnosed
based on the presence or absence of clinical signs & symptoms and status of immune function. (CD4 is < 1,500)
TRANSMISSION PREVENTION
Transferred from mother to child during Screen all pregnant women for HIV (& repeat in 3rd trimester if high risk)
in utero ✚HIV (before or at 48 hrs) most Reduce risk of infection of maternal infection by using clean blood & tissue
common mode of transmission
, intra-partum (✚HIV supplies, STD prevention, & avoiding needle sharing
after 1 week old), or through Chemoprophylaxis to reduce risk of perinatal HIV by treating pregnant
breastfeeding. mother and infant → Prophylaxis includes the administration of 3 ARV drugs
If HIV status unknown at the time of birth, conduct a from at least 2 different classes (cART) → all ✚HIV-1 pregnant women
rapid HIV-1 antibody test given AZT during labor
Can also be transmitted though sexual activation Elective C-section @ 48 wks if pregnant woman has viral load of >1000/mL
(common in adolescence), contaminated blood products,
needle-stick injuries, sharing utensils.
CARE OF THE HIV-1 INFECTED INFANT 1. Review h/o possible maternal co-infections 2. Evaluate infant for s/s of co-infection
DIAGNOSTICS SYMPTOMS MANAGEMENT
3. Conduct baseline lab work includes CD4 T-lymphocyte count, Prematurity 5. All HIV-
CBC w/ diff, & platelet. Low birth exposed newborns
Other labs: CMP, AST/ALT, Albumin, total protein, weight/FTT/ should be treated
phosphate, calcium, HIV RNA, drug resistance testing, lipid ↓weight w/ zidovudine
panel, UA Recurrent bacterial usually within 6-
4. Test for active HIV-1: or viral infection 12 hrs but at least
Neonate: Direct viral assays tests (HIV DNA polymerase chain reaction & HIV RNA assays) (i.e. oral thrush) before 12 month
@ 14-21 days, 1-2 months, 4-6 months. Repeat 2-4 wks after stopping ARV therapy. To Developmental of age.
definitely exclude HIV, need 2 negative (-) tests after 6 months and 1 negative (-) direct delays 6. Start
HIV viral assay after 1 month and a 2nd after 4 months. Recurrent fever w/ pneumocystis
Children & toddlers: Nucleic acid amplification tests (NATs) (HIV DNA tests, RNA fatigue carinii pneumonia
polymerase chain reaction assays (PCR tests), RNA quantitative or qualitative assays Skin rash’s prophylaxis in
Adolescents & children ≥24 mo: 4th generation p24 antigen, anti-HIV IgM & IgG (shingles, herpes) infants at 6 wks
antibodies (positive results must be followed by an FDA approved immunoassay test that Oral ulcers regardless of CD5
differentiates b/w HIV-1 & HIV-2 (See below ↓) Diarrhea/abd count
pain/GI upset 7. Standard
Lymph-adenopathy, immunizations
Genital STD’s given
SOB on exertion, 8. Refer to
dry cough infectious disease
specialist for co-
infections
9. Measure CD4
T-lymphocyte q
6-12 months in
children who are
adherent to
therapy, have high
CD4 counts,
sustained viral
infection, or have
stable clinical
status for >2-3
yrs)
CHLAMYDIA: most common STI in US (1-wk ETIOLOGY SIGNS/SYMPTOMS (common)
incubation) Human infection Neonatal
(3 species): conjunctivitis:
chlamydia occurs 5-14 days
trachomatis, after birth (as late
chlamydophila as 5 weeks), lasts >
pneumonia, & 2 wks,
chlamydophila conjunctival
Conjunctivitis, trachoma, or pneumonia is transmitted psittaci,→Obligat edema & exudate,
to neonate from untreated maternal infection, & genital e intra-cellular watery to muco-
tract infection, trachoma, & lymphogranuloma infectious purulent eye
venereum bacterium (see discharge, eyelid
life cycle) swelling
(outside of the U.S., most commonly causes ocular prophylactic eye
disease leading to blindness) treatment used for
GC not effective
for chlamydia.
Neonatal pneumonia: occurs 3-19 wks old
(incubation 7-21 days), early signs rhinorrhea,
congestion, conjunctivitis followed by tachypnea w/
persistent “staccato” cough, congestion, & rales
(preterm infants may have apnea), afebrile
Genitourinary tract
infections: urethritis,
cervicitis, endometritis,
perihepatitis
DIAGNOSTICS TREATMENT
GOLD Prophylactic eye treatment used for GC not effective
STANDARD: for CT.
Tissue culture Topical therapy not effective
containing
epithelial cells
(FDA Erythromycin, Oral suspension, 50mg/kg/day, for
approved for 14 days, may need 2nd coarse in infants, infant at ↑
any site of risk for hypertrophic pyloric stenosis
infection)
Nucleic acid
amplification tests
(NAATs): good for
vaginal or urine of
asymptomatic
women, cervical if
symptomatic, or
urine for males (not
approved for extra-
genital sites)
Enzyme immunoassays (EIAs):
for prenatally acquired vaginal &
rectal infection up to 18 months
(after that suspect abuse)
Chest radiograph: hyperinflation w/
bilateral interstitial or patchy
infiltrated (no lobar consolidation or
pleural effusion)
Peripheral Eosinophilia (>400 cells μ/L)
Pneumonia: Serum acute micro-immunoflourecent
(MIF) titer for IgM if 1:32 or more

GONORRHEA: ETIOLOGY SIGNS/SYMPTOMS (common)

2nd most common STI in Maternal Ophthalmic: swollen, injected conjunctiva & eyelid w/ exudate occurring 2-5 days after birth (up to 25 days). Thin
15-24 year old women. transmission to clear discharge from eye becomes thick, mucoid, & sometimes bloody (if left untreated, will progress to edema, cornea
neonate from ulceration, blindness, & possible systemic infection)
Infections caused by the contact with Disseminated gonococcal infection (DGI): Polyarthralgias, tenosynovitis (fever, malaise, chills,
acquisition of Neisseria vaginal birth irritability), dermatitis, triad, purulent arthritis (no systemic symptoms)
gonorrhoeae that occurs secretions
only in humans. DIAGNOSTICS TREATMENT
Gram stain (at initial evaluation): Ophthalmia neonatorium prophylaxis: silver nitrate 1% aqueous, Erythromycin
gram (-) intracellular diplococcic in ophthalmic ointment 0.5%, tetracycline ophthalmic ointment 1%.
smears of exudate Hospitalize infected neonates & evaluate for disseminated disease
Conjunctivitis w/o dissemination: Ceftriaxone, 25-50 mg/kg, IV/IM single dose
Culture (preferred): swab from orifice (max 125 mg, Cefixime is recommended for infants with hyperbilirubinemia)
or blood, synovial fluid from affected Disseminated infection: Ceftriaxone, 25-50 mg/kg, IV/IM single dose for 7 days
joint or CSF (10-14 days if meningitis is documented) OR Cefixime 25 mg/kg IV/IM q 12 hrs
for 7 days (10-14 days if meningitis is documented)
Nucleic acid amplification tests (NAATs) are not approved for pre-pubertal children
CONGENITAL SYPHILIS: an infection caused by Treponema pallidum, a spirochete, an can be
acquired in adolescents and congenital in infants though trans-placental transmission
ETIOLOGY ↑RISK SIGNS/SYMPTOMS
Mother with h/o untreated Higher in MSM, May be asymptomatic at birth during first week of life
syphilis (transmission occurs black & Hispanic Early congenital syphilis: Low birth weight, prematurity, rhinitis,
more easily when mother has 1° women, cocaine jaundice w/ ↑ALT/AST, lymphadenopathy w/ coombs (-) hemolytic
or 2° infection.) If mother has abusers, lack of anemia, thrombocytopenia, osteochondritis (resistant to movement),
untreated early stages, often prenatal care rash, CNS abnormalities,
results in spontaneous abortion. Late congenital syphilis (b/w 5-20 yrs): interstitial keratitis, Hutchinson teeth, bowing of the shins, symmetrical
joint swelling, saddle nose, frontal bossing, molars with enamel growth, fissures or cracks in skin, nose and mouth
DIAGNOSTICS TREATMENT
1. Treponemal tests (done 1st in neonatal timeframe): All pregnant women should obtain prenatal screening and treated if infected
fluorescent treponemal antibody absorption (FTA-
ABS) and Treponema pallidum particle agglutination Treat infants with proven or highly probable disease (via abnormal physical exam, Non-
(TP-PA) (will be positive for life and do not detect Treponemal tests, or ✚ Dark-field microscopy tests:
new infection, not confirmatory) →Aqueous crystalline penicillin G 100,000-150,000 U/kg/day given as 50,000 units/kg/dose IV
2. Non-Treponemal tests→ rapid q 12 hrs during 1st 7 days of life or q 8 hrs if the infant is older then 1 week for a total of 10 days
plasma reagin (RPR), venereal OR
disease research laboratory (VDRL) →Procaine penicillin G 50,000 units/kg/dose IM in a single dose for 10 days
3. Dark-field microscopy tests & direct fluorescent Follow up to determine appropriately falling titers of Non-Treponemal serologic tests q 2-3
antibody (DFA) test: Allows for direct visualization months until a fourfold decrease or the test becomes nonreactive.
of spirochete (definitive diagnosis)
When a child has a reactive serological test after 1 months of age, mother should be tested also to
*If mother has reactive tests (i.e. confirmatory diagnosis), the infants determine if the child has congenital or acquired syphilis & treat with:
cord blood should be evaluated with quantitative VDRL or RPR →Aqueous crystalline penicillin G 200,000-300,000 U/kg/day q 4-6 hrs for 10-14 days
Abnormal lab values: ↑ALT/AST, ✚VDRL(csf), coombs (-)
hemolytic anemia

CONGENITAL HERPES: group of infectious disease caused by HSV type 1(primary source of oral herpes, usually affecting skin
above the waist & face) or 2 (source of genital herpes, usually effecting skin below the waist). HSV infection during newborn period (high
mortality rate even with treatment) consists of:
1. Disseminated disease involving multiple organ systems but mostly the liver and lungs
2. Localized CNS disease
3. Skin, eyes, and/or mouth disease
Over 80 strains exists, of which, 8 are able to infect humans (HSV-1, HSV-2, EBV, CMV, Kaposi’s sarcoma-associated herpes virus)
TRANSMISSION SIGNS/SYMPTOMS
Contact w/ open In urero infection: usually fata, if survive to term, causes vascular lesions, chorioretinitis, microphthalmia (small eye),
lesions or mucous microcephaly & CNS disease
membranes. In Neonatal skin-eye-mouth disease (1st 2 wks of life): cutanous vesicles on scalp, mouth, nose, eyes with erythematous
neonates, can base, clear & cloudy fluid, sometimes pustularm limited skin, eyes, & mouth.
occur in urero, Neonatal CNS disease (2nd & 3rd wk of life): lethargy, irritability, poor feeding, temperature instability, seizures, apneic
peripartum, or episodes, permanent neurologic disability, herpetic leasions (60%), cranial nerve abnormatlities, seizures.
postnatally. Neonatal disemminated disease (acutely ill during 1st week of life): seizures, fever, tachypnea, sepsis & shock,
disseminated intravascular coagulation, multiorgan failure with liver (hepatomegaly) and lungs (pneumonitis) mostly
effected, unresponseive to antibiotics.
DIAGNOSTICS TREATMENT
Direct fluorescent antibody (w/ active skin lesions) Neonatal skin-eye-mouth disease: Acyclovir, 20 mg/kg IV q 8 hrs for
Polymerase chain reaction (PCR) (for CNS 14 days (60 mg/kg/day)
infections) →Ocular involvement: 1% trifluridine, 0.1%
Serologic testing rarely useful iododeoxyuridine, 3% vibarabine (HSV specific)
Chest radiograph: bilateral patchy infiltrates from 3-10 Neonatal CNS disease: Acyclovir, 20 mg/kg/day IV q 8 hrs for 21
days of neonatal disseminated disease days, 5 times/day for 7-10 days (60 mg/kg/day)
Lab Values: ↑ALT/AST, ✚protein & ↑WBC’s in CSF Neonatal disemminated disease: Acyclovir, 20 mg/kg IV q 8 hrs for
21 days, 5 times/day for 7-10 days (60 mg/kg/day

CYTOMEGALOVIRUS (CMV) most common intrauterine infection: Congenital infection with CMV, which is a member of the herpes virus
family, can be symptomatic or asymptomatic (more common). Some asymptomatic infants at birth develop hearing loss and learning
disabilities later in life.
TRANSMISSION ↑RISK SIGNS/SYMPTOMS
can occur in urero Low birth weight, Some asymptomatic infants at birth develop sensorineural hearing loss (most common)
(via placenta), premature infants (via and learning disabilities later in life.
peripartum (passage breast milk), low Neonatal acquisition often present as afebrile
during birth), or socioeconomic groups, pneumonia after 8 wk incubation periods
postnatally (via African American, & in Intrauterine growth restriction, developmental
breast milk) developing nations. delay, jaundice, hepato-splenomegaly, purpura,
generalized petechiae, thrombocytopenia, bone
abnormalities, periventricular calcification,
seizures, sensorineural hearing loss,
microcephaly, retinitis, pneumonitis
DIAGNOSTICS TREATMENT
→Isolate CMV from infant urine, pharynx, or Primary prevention in women of childbearing age most important
peripheral blood leukocytes in the 1st 3 wks of life Congenitally infected infants (symptomatic or CNS involvement): IV ganciclovir 6
PCR Testing of neonatal blood and CSF mg/kg for 6 wks OR Valganciclovir 16 mg/kg/dose q12 hrs (monitor for
CMV specific IgM (four fold increase) used neutropenia←will need to restore neutrophil count using colony-stimulating factor)
beyond neonate period Antiretroviral not recommended in asymptomatic infections – conduct routinely for
CMV antigenemia audiology deficits, growth retardation, developmental & learning disabilities

CONGENITAL RUBELLA (Germen Measles) SYNDROME: Rubella is the Rubivirus in the togaviridae family. It is mild in most
adults but when it infects a fetus (1st 12 weeks of gestation), it can cause multisystem involvement and congenital defects (incubation
ranges from 12-23 days with mean of 18)
TRANSMISSION SIGNS/SYMPTOMS
Maternal to fetus Early manifestation (diagnosis made on symptoms): Ophthalmologic (cataracts,
pigmentary retinopathy, microphthalmos, congenital glaucoma), Neurological
(behaviors disorders, meningoencephalitis, MR, developmental delay,
microcephaly), Cardiac (PDA, peripheral pulmonary artery stenosis) Auditory blueberry muffin lesions
(deafness), Growth (FTT related to heart defects), Skin (purpura, jaundice,
dermal erythropoiesis i.e. blueberry muffin lesions, petechiae)
Delayed manifestations (up to 2-4 yrs): DM, progressive encephalopathy, autism,
DIAGNOSTICS TREATMENT
✚ Viral culture Isolate infant from infected mother for 1 full year (even if child is asymptomatic
PCR testing but the mother has a confirmed infection)
✚ rubella specific antibody Educate on teratogenicity of rubella infection during pregnancy
(↑IgM antibody) Refer to appropriate specialist (cardiology, ophthalmology, audiology)
Thrombocytopenia Early developmental stimulation & appropriate school placement
Report to state public health department

HEPATITIS B (most common in the world): Hepadnaviridae virus that primarily effects the liver
that can cause an acute hepatitis with recovery or liver failure or chronic hepatitis with
cirrhosis, carcinoma, or liver failure. If prenatally infected neonate (24% of infections)
is left untreated, will cause lifelong chronic infection (can also results in “healthy”
chronic carrier state)

→70-90% of infants acquire the disease from ✚HBsAg & ✚HBeAg mother if not
given post-exposure prophylaxis (↓chance if mother only has ✚HBsAg)

HBcAg (core antibody) = appears at the onset of symptoms in acute hepatitis B and
remains for life
TRANSMISSION INCUBATION SYMPTOMS
Close personal contact, saliva, blood Long incubation Malaise, anorexia, nausea, vomiting, RUQ abdominal pain, fever, headache,
or body fluids, & perinatally during time: 60-160 days arthritis, arthralgia, myalgia, skin rash/urticaria, dark urine (1-2 days before
birth (can survive >1 wk off host) (average 90) onset of jaundice
DIAGNOSTICS MANAGEMENT
✚HBsAg (surface antigen) = Chronic infection occurs if − IgM Anti-HBc or ✚HBsAg for > 6 months
acute (earliest marker) or post-exposure prophylaxis to prevent perinatal transmission: HBIG 0.5mL 1 vaccination in 1st 12 hrs of
chronic hepatitis B infection, life, 2nd dose must be given at 1-2 month with 3rd dose at 6 months (infant should be tested for HBsAg
persistence > 6 mo indicates & Anti-HBs @ 9-18 months to evaluated successful vaccination.
carrier status Hepatitis B vaccine available and highly recommended for all newborns & adolescents starting at birth
✚ IgM Anti-HBc = indicates FDA approved drugs to treat Hepatitis B:
recent (acute) infection within Interferon if ≥ 1 year (expensive & ✚ side effects)
the last 6 months Lamivudine 3 mg/kg/day if interferon fails & ≥ 3 years
✚Anti-HBs = immune status Adefovir 10 mg/day for children >12 years
after resolved infection & Telbivudine if ≥ 16 year
immunization Entecavir 0.5 mg daily for children >2 years
↑Aminotransferase(peak 1 mo) Refer to specialist for treatment
↑Birubin, ↑WBC, ↑serum α- For adults, with chronic hepatitis or liver failure, treatment includes Interferon a-2b & Peginterferon a-
fetoprotein 2a for chronic cases AND/OR long-term use of lamivudine, adefovir, telbivudine, entecavir, tenofovir

TOXOPLASMOSIS: Toxoplasma is an obligate intracellular protozoan that causes an infection after consumption of undercooked meat
or ingestions of the oocyte od T. gondii from unwashed fruits & vegetables. Can also be transmitted through a definitive host such as a
domestic or feral cat that excretes oocytes in soil or litter which transmits it to human)
TRANSMISSION INCUBATION SYMPTOMS
→Consumption of 4-21 days (average 7 days) Primary infection in children is usually
undercooked meat self-limiting and presents as & occipital
or unwashed fruits cervical adenopathy most common sign
& vegetables accompanied by non-specific
→Handling soil or Symptoms of malaise, fever, sore throat, arthralgia, & myalgia
litter containing Neonate often asymptomatic at birth (70-90%) but may develop symptoms later
domestic or feral Acute infection during pregnancy (classic triad): 1. Chorioretinitis (acutely
cat excretions causes blurred vision, eye pain, floaters, scotoma, & photophobia but often results
Highest rate of in blindness later) 2. Intra-cranial calcifications 3. Hydrocephalus
transmission to Non-specific manifestations of acute congenital infection: Microcephaly or
fetus b/w 10-24 Hydrocephalus with or without Intra-cranial calcifications, seizures,
wks gestation maculopapular rash, hepatosplenomegaly, jaundice, thrombocytopenia, retinal
(greatest burden of lesions, growth failure, lymphadenopathy
disease during this Late manifestation’s: blindness, retinal lesions, epilepsy, psychomotor
timeframe) retardation, mental retardation (as late as 2nd or 3rd decade)
DIAGNOSTICS MANAGEMENT
Prenatal: fetal blood or tissue analysis, ultrasonography, Primary prevention & education in women of childbearing age most
symmetrical ventriculomegaly, PCR assay of amniotic fluid, important (avoid undercooked meat, always wash fruits & veggies before
immunoperoxidase staining w/ any fluid for confirmation consuming, wear gloves while gardening, and avoid changing litter boxes.
Indirect methods for high risk pregnant women → For symptomatic & asymptomatic congenital infection: pyrimethamine
Organism specific serology IgA, IgM (present 2wks – 6-9 combine with sulfa-diazine supplemented with folic acid for 1 year is the
months post infection), IgG (positive 1-2 months after initial therapy along with consultation from infectious disease specialists
infection & must be sent to PAMF-TSF for confirmation) For maternal infection: spiramycin (investigational drug) in pregnant
Direct methods: view fluids & tissues under microscope & women to prevent transmission to fetus (only works if fetus not already
evaluate DNA PCR of bronchoalveolar lavage fluids infected & requires FDA & PAMF-TSI consultation.
Visual detection of tachyzoites in newborn CSF, ventricular If fetal infection confirmed after 18 wks or mother acquires infection
fluid, blood, bone marrow, brain or placental tissue during 3rd trimester: maternal treatment with pyrimethamine combine
with sulfa-diazine

FETAL ALCOHOL SPECTRUM DISORDERS (FASD): an umbrella term for a set of disorders that
results from the consumption of alcohol during pregnancy leading to a wide range of features
characterized by facial dysmorphia, growth deficiency, & CNS symptoms.
TYPE DESCRIPTION
Fetal alcohol syndrome (FAS) Full blown syndrome involving every diagnostic feature as outlined above
Partial Fetal alcohol syndrome (FAS) Some, but not all of the facial features present, CNS dysfunction remains
Alcohol related neurodevelopmental CNS abnormalities without any facial abnormalities & confirmed prenatal exposure
disorder (ARND)
Alcohol-related birth defects (ARBD) Various birth defects without CNS disease & confirmed prenatal exposure
Static encephalopathy/ alcohol exposed Significant structural defects & neurological defects but no growth retardation or facial
(SE/AE) features
Neurodevelopmental disorder (alcohol Confirmed prenatal exposure w/ cognitive & behavioral problems (difficulties with
exposed) math, memory, attention, school, impulse control) but no CNS damage
ETIOLOGY SYMPTOMS DIAGNOSTICS FEATURES MANAGEMENT
✖Can occur even at low ✖h/o drinking during ✖Thin upper lip w/ vermilion border ✖Prevention &
levels of consumption (cell pregnancy ✖Short palpebral fissures, wide spaced eyes education is most
adhesion molecules are ✖Infant EtOH ✖Flattened philtrum, important so that mom
inhibiting which affects withdrawal symptoms ✖Short, upturned beaklike nose & broad nasal knows the risks associate
neuronal migration) (irritability, bridge with her behaviors.
✖Alcohol increases hyperactivity, ✖Micrognathia (undersize jaw), dental malocclusion ✖No treatment for
acetaldehyde level, which jitteriness) ✖Cleft palate primary deficits
causes apoptotic damage ✖Maternal amniotic ✖Growth retardations (can be prenatal or postnatal)
from excess glutamate fluid odor of alcohol is ✖CNS dysfunction (intellectual
activity after GABA used within the last disability-✖IQ 60-80, ADHD, conduct
withdrawal. This leads to few days before birth disorders, anxiety, sleep disorders,
apoptotic neuro-degeneration ✖Abnormal facial language delays, memory impairment)
reaction deleting neuron from features, growth ✖Microcephaly
developing sites in the CNS retardation, structural ✖Congenital heart defects
→1 drink/wk of prenatal or functional CNS ✖Limb deficiencies and/or Hip
alcohol exposure is problems & h/o ✖dislocation
associated w/ aggressive prenatal alcohol ✖Seizure disorder
behavior at 6-7 years exposure ✖Hearing & vision problems
(myopia, strabismus)
GENETIC SYNDROMES

TRISOMY 18 (Edwards Syndrome):

KARYOTYPE ETIOLOGY FEATURES DIAGNOSTICS MANAGEMENT
47 XY or XX 1 18 Advanced maternal ● Growth retardation Karyotype (fluorescent Genetic counseling
Trisomy of chromosome 18 age (non-disjunction (FTT) in-situ hybridization Psychosocial support
during meiosis) ● Microcephaly, low- analysis available within Refer to cardiology if
set eyes, prominent 48 hrs) murmur heard for
occiput, micrognathia Maternal serum prophylactic
● Clenched hands, quadruple screen (α- antibiotics (prevents
rocker-bottom feet & fetoprotein, hCG, sub-acute bacterial
overlapping fingers unconjugated estriole, endocarditis)
● Congenital heart inhibin A) Support nutritional
defects Echocardiogram needs, may need
● MR & gross Chronic villus sampling parenteral feeding
● delays or amniocentesis with Early intervention &
● Hypertonia subsequent pregnancies special needs care
● Feeding problems

DOWN SYNDROME (Trisomy 21): most common inherited genetic syndrome (composed of 3 different genetic alterations
TYPE ETIOLOGY FEATURES DIAGNOSTICS MANAGEMENT
47 XY or XX 1 21 Advanced ● Mild to severe MR ↑risk for congenital Karyotype, Screen for common Primary prevention
maternal age (IQ 20-70) heart defects other issues (TSH, CBC, celiac) (educate about risk
or any familial ● Midface (mostly endocardial factors)
chromosomal hypoplasia, epicathal folds, cushion defect Secondary prevention
abnormality flat nasal bridge, upward &VSD), (prenatal diagnosis
(random non- slanting palpebral fissures, hirschsprung, GI Conduct Eye exams
disjunction) brushfield spots, small mouth atresia’s,, hip every 2 years (esp b/w
& ears, excessive skin at nape dislocation, hearing age 3-5)
of neck loss, otitis media, Early intervention
● Simian crease & hypo-thyroidism, (PT/OT/speech, special
short 5th finger w/ celiac, leukemia, education)
clinodactyly (bent) cataracts, obesity. Genetic counseling
● Wide space b/w 1st Premature aging Nutritional support
& 2nd toe
● Hypotonia,
hyperflexicility
● Dry skin

FRAGILE X SYNDROME most common inherited cause of MR: a disorder linked to a fragile site on the long arm of the X chromosome at band
q27.2 (over 200 repeats of CGG in the coding protein of the fragile X retardation protein gene (FMRP)
ETIOLOGY FEATURES SIGNS DIAGNOSTIC MANAGEMENT
 Dependent on Males are ● Strabismus w/ refractive errors DNA analysis Genetic testing should be
the amount of more ● Long, narrow face, prominent jaw, from whole done in anyone with family
FMRP levels severely high arched palate, dental crowding, malocclusion blood (confirms history of MR, disabilities or
effected ● Protuberant ears, chronic OM diagnosis) autism, infertile women with
because they ● Macroorchidism Prenatal testing ↑FSH who are < 40 years, &
have only (>80%) via chorionic egg/sperm donors
one X ● Soft, velvet skin villus or Genetic counseling
chromosome ● Joint hypermobility amniocentesis Psychosocial support and
● Pes planus, scoliosis, management of behavioral
clubfoot problems with
● Seizures, psychotropic medications
macrocephaly, speech delay, Regular heart, ear, eye, &
echolalia developmental evaluations
● Poor gross motor Early intervention (speech,
coordination sensory/motor, special ed)
● Poor eye contact,
excessive shyness & anxiety w/
hand flapping & biting
● Tactile defensives
● ADHD, hyper-arousal
to sensory stimuli, autism
● Heart murmur,
GERD

TURNER SYNDROME (XO karyotype):

TYPE ETIOLOGY SYMPTOMS DIAGNOSTIC MANAGEMENT
45, X 45, X/46,XX Non-disjunction ● Female w/ growth failure & pubertal Cytogenic testing Refer to
Structurally abnormal X during meiosis delay for Karyotype endocrinology for
● Neonatal edema of hands or feet Echocardiogram growth hormone
(Resolves by age 2) Pelvic ultrasound therapy & estrogen
● Low hairline, high arched palate ↑FSH replacement
● Nuchal folds (webbed neck) therapy at about
● Widened, inverted nipples, “shield” chest 12-13 years of age
● Left sided cardiac anomalies (coartation Genetic counseling
& hypoplastic) Psychosocial &
● Low set or deformed ears, chronic OM educational
● Small mandible, defective dentition support
● Short stature, IUGR, Scoliosis Refer to
● Cubitus valgus cardiology,
● Nail hypoplasia, Short 4th metacarpal ophthalmology,
● Multiple pigmented nevi ENT, orthodontist,
● Strabismus, amblyopia, ptosis urology, &
● Horseshoe kidney orthopedist

KLINEFELTER’S SYNDROME (XXY karyotype): most common chromosomal disorder in males, most common cause of
hypogonadism & infertility in men. → often goes undiagnosed until adulthood

ETIOLOGY FEATURES DIAGNOSTIC MANAGEMENT

47, XXY Advanced ● Slow, incomplete pubertal development ↑risk for mediastinal & ↑Gonadotropin Early intervention for
(male maternal age (sparse facial hair, small & firm testes >10 breast cancers, cleft palate ↓Testosterone learning issues
with 2 (maternal meiotic mL volume, infertility) ↑ FSH & ↑LH Counseling/therapy
X’s) non-disjunction ● Tall, eunuchoid body proportions, Azoospermia for behavior issues
during meiosis) abnormally long legs Encourage exercise
● Gynecomastia Psychosocial support
● Metabolic syndrome w/ abdominal for family
obesity (DM type 2) Genetic counseling
● Behaviorally shy, immature, anxious, Referral to pediatric
aggressive, & antisocial endocrinologist to
● Osteoporosis consider
● Learning disabilities (reading, spelling testosterone therapy
& syntax problems, speech & language at age 11 or 12
dysfunction, impaired executive function)
● Poor libido, erectile dysfunction

TAY-SACHS DISEASE: inborn error of metabolism, which leads to a deficiency of

hexosaminidase A. This lysosomal storage disease, classified as sphingolipidosism, results in the
accumulation of Gm2 ganglioside in the lysosomes of various tissues. As glycosidase accumulates
in the neurons, axons degenerate and demyelination occurs resulting in progressive neurologic
degenerative disease & death.
TYPE ETIOLOGY SYMPTOMS FEATURES DIAGNOSTICS MANAGEMENT
Autosomal recessive Hexosaminidase A Deficiency (Hex A) ● Normal development till 3-6 More Gene testing for Genetic counseling
transmission of HEX A months then progressive common in known mutations 1° prevention
gene on chromosome 15 deterioration occurs Ashkenazi Serum enzymatic (carrier screening)
 ● Irritability & ↑reaction to Jews, assay yields ↓ 2° prevention
sound w/ emerging spasticity Pennsylvania Hexosaminidase A (prenatal diagnosis &
(1st signs) Dutch, More white matter elective pregnancy
● Hypotonia, developmental Louisiana myelination on MRI termination)
delay Cajun & No known treatment
● Vision deteriorate by 6 French Supportive care,
months & blind by 1 year Canadian nursing services,
(cherry red spot on macula) Psychosocial support
● Macrocephalic for family
● Frequent URI’s
● Seizures

MARFAN SYNDROME: inherited disorder of connective tissue

ETIOLOGY SYMPTOMS [Ghent diagnostic criteria] DIAGNOSTICS MANAGEMENT
Autosomal ● Long & narrow face Genetic testing Referral to cardiology
dominant ● Dolicocephaly (long, narrow head) downward to evaluate (echocardiogram),
FBN1 mutation inheritance of slanting palpebral fissures, enophthalmos, malar defects in FBN1 ophthalmology (treatment of
on chromosome defective hypoplasia, retrognathia (no chin) Positive family myopia), endocrinology
15 [15q21.1] fibrillin gene ● Pectus excavatum/chest asymmetry history (hormonal therapy)
● Arachnodactyly (long, thin fingers), Psychosocial support for
● Scoliosis or kyphosis family
● Abnormal body proportions, ↑arm & leg Genetic counseling
length, thin extremities Ensure mainstream inclusion
● Vision problems (myopia, enophthalmos) with necessary cardiac sports
● External ear abnormalities restrictions
● Cardiac problems (heart murmur, dilated
aortic root)
● Hypotonicity & joints hyperextension

PRADER-WILLI SYNDROME:
ETIOLOGY SYMPTOMS DIAGNOSTICS MANAGEMENT
A failure of expression of the Infancy: hypotonia, FTT, feeding FISH to look at PWS region Behavioral therapy for
paternally acquired problems, weak & squeaky cry, eating & psychological
imprinted region on dolichocephaly problems
chromosome 15q11-q13 Childhood: Voracious uncontrollable appetite, Genetic counseling
primarily effects the obesity, short stature, upward-slanting palpebral Early intervention
neurological & endocrine fissures, thin upper lip with downturned corners, (speech, sensory/
system hypopigmented skin, global developmental delays, motor, special ed)
behavioral problems (temper tantrums, OCD, Referral to pediatric
stubbornness, skin picking, psychosis, perseverant endocrinologist to
speech), sleep apnea w/ ↓RR, early morning considers growth
wakening, daytime sleepiness, temperature hormone therapy
instability, hyper-nasal speech, small genetalia

MUCOPOLYSACCHARIDOSIS (MPS): Rare group of lysosomal storage disorders of glycosaminoglycan (GAG) catabolism leading
to accumulation of partially degraded GAG due to a specific lysosomal enzyme deficiency. Accumulation of GAG fragments causes
progressive cellular damage in multiple organ systems leading to organ failure.
TYPE ETIOLOGY SYMPTOMS DIAGNOSTIC MANAGEMENT
Almost all are MPS I (Herler- ●Orthopedic (profound loss of joint motion, restricted mobility & Prenatal testing Enzyme replacement therapy w/
autosomal Scheie syndrome): growth, skeletal abnormalities, scoliosis, hip dislocation, short stature, via chorionic human recombinant enzyme
recessive deficiency of dysostosis multiplex, kyphosis) villus or Hematopoietic stem cell transplant
(except MPS lysosomal enzyme ●Neurologic (macrocephaly, scaphocephaly, severe to mild cognitive amniocentesis can reserve intellectual capacity
II which is X- α-L-iduronidase impairment, placid behavior) Psychosocial support for family
linked) ●Eyes (cornea clouding, retinal degeneration) Early intervention
Attenuated MPS I ●HEENT (deafness, snoring & coarse breathing due to adenoidal & MRI of brain & spine
can go tonsillar hypertrophy, enlarged tongue, full lips, flat nasal bridge, Routine hearing,
undiagnosed for communicating hydrocephalous) vision,
years with no ●GI (recurrent inguinal hernia, hepatosplenomegaly) pulmonary
cognitive ●Respiratory (restrictive lung disease, sleep apnea, asthma, Recurrent function tests,
impairment URI’s with otitis) sleep studies
●Cardiac (CHF, valvular disease, angina, HTN) Gold standard: Laronidase (aldurazyme)
MPS II (Hunter syndrome): deficiency of enzyme activity Idursulfase (Elaprase)
lysosomal enzyme iduronate-L-sulphatase assay based on
MPS III (sanfilippo Hyperactive cultured
syndrome): subtype of Aggressive leukocytes,
enzyme in MPS II plasma, serum,
MPS IV (Morquio syndrome) & fibroblasts Sulface alfa
MPS V (Scheie syndrome) Measure
urinary GAG
MPS VI (Maroteauz-lamy syndrome)
levels
MPS VII (sly syndrome)
MPS IX: deficiency of
lysosomal enzyme hyaluronan
MULTISYSTEM DISORDERS

CEREBRAL PALSY: a group of static disorders that affect development of motor control, posture, & balance due to a permanent
static injury to the developing fetal or infant brain.
ETIOLOGY SYMPTOMS DIAGNOSTIC MANAGEMENT
Prenatal causes ●Abnormal muscle tone ↑risk if born prematurely Delayed developmental Early intervention (PT/OT/speech, special ed)
(in utero stroke, ●(hyper- or hypo-tonia) & low-birth weight. milestones, gross motor, Treat associated conditions (seizures, visual & hearing
brain mal- ●Muscle weakness ↑risk for vision & hearing fine motor, speech impairment, GERD) & refer accordingly
formation, ●Persistent infant reflexes impairments, seizures, Brain MRI (if not done Prevent secondary conditions (FTT, skin breakdown,
congenital CMV ●Hyperreflexia cognitive impairment, prenatally) to ID utero dental caries)
infection) ●Restricted joint ROM dental disease, sleep issues strokes, brain malformation, Functional therapies (adaptive seating, bracing,
Perinatal causes ●✚ hip click white matter loss wheeled mobility)
(hypoxic ischemic (Ortilani/Barlow) Psychosocial support for family
encephalopathy, ●Scoliosis Nutrional support, gastrostomy if needed
viral encephalitis, ●Swallowing & feeding Oromotor therapy (chewing, swallowing, speech)
meningitis) difficulties Supplement anticonvulsant treatment with calcium and
Postnatal causes ●Respiratory problems vitamin D
(accidental head ●Incontinence Spasticity Relief Medications:
trauma, anoxic ●Movement related muscle ★Enteral medications (lioresal, diazepam, dantrium
insult, child abuse) spasms w/ spasticity sodium, tizanidine hydrochloride)
●Infant may show hand Intramuscular medications (Botulinum toxin, nerve
preference before 12 blocks)
months old ★Intrathecal medications (lioresal)
●May scissor legs when ★Selective dorsal root rhizotomy
held under the arms

TYPES
SPASTIC ATHETOLD (DYSKINETIC) ATAXIC (HYPOTONIC) MIXED

SPINA BIFIDA: Congenital abnormality of CNS or spine resulting in failed neural tube closure during early embryologic development
ETIOLOGY SYMPTOMS DIAGNOSTICS MANAGEMENT
Multifactoria ●Neurological (can have hydrocephalus, chiari ↑risk if Prenatal screening Infants diagnosed prenatally should be referred
l & not well malformation, hydromyelia, or tethered cord, widely mother has for ↑ α-fetoprotein to tertiary care center with appropriate birth
understood spaced cranial sutures, bulging fontanel, macrocephaly) folic acid Prenatal Ultrasound supports (i.e. planned C-section, NICU placement)
Additional of ●Orthopedic (hip dislocation, knee contractors, deficiency, for spinal anomaly & Refer to multidisciplinary teat (orthopedist,
folic acid to scoliosis, kyphosis, or spine fractures, ↓lower extremity use valproic head “lemon sign” urologist, neurosurgeon, developmental pediatrician,
dietary intake function, clubfoot, tibial torsion, atrophied lower acid, Increasing head orthotist, PT/OT, nutritionist, APN, social worker)
↓incidence by extremity muscles) carbamazepi circumference after Early intervention
50% ●Urological (dripping, incontinence, frequent UTI’s, ne, or has birth Monitor for UTI’s (w/less common organisms),
uretal reflux w/ renal damage, neurogenic bladder) DM shunt malformations w/ hydrocephalous, ↑ICP,
●GI (chronic constipation, bowel incontinence, tether cord, baseline head CT & refer to
neurogenic bowel) neurosurgeon if suspected
●Motor development delays (especially lower Monitor for skin breakdown
extremities) Nutritional & behavioral intervention to prevent
●Latex allergies obesity
●Abnormal DTR's & neonatal reflexes in lower Test for latex sensitivity
extremities Psychosocial support for family
●Absent anal wink Genetic counseling
●Older children often obese All women of childbearing age should consume
●Sometimes have learning difficulties like ADHD 0.8 mg folic acid daily to prevent neural tube
defects
SPINA BIFIDA OCCULTA ARNOLD-CHIARI II CNS MALFORMATION MENINGOCELE OR MYELOMENINGOCELE
Sacral dimple, hairy patch at base of spine, Progressive hydrocephalus, difficulty swallowing, Lesion along thoraco-lumbar-sacral spine (protruding cyst-like
uneven gluteal folds (Benign) hypoventilation, apnea structure may have visible neural elements in it)
SUDDEN INFANT DEATH SYNDROME (SIDS): The death of infants who are young
then 1 year without a physiologic cause despite a complete examination of the case
(including autopsy, examination of the scene of death, review of medical history & record).
ETIOLOGY FEATURES SYMPTOMS DIAGNOSTIC MANAGEMENT (Risk Reduction)
Unknown → believe to Higher rates in Infant is Diagnosis of ✖Encourage prenatal case
be related to co-sleeping non-Hispanic suddenly found exclusion with ✖Supine sleep position (no side-lying) with “tummy time” during the day and
Possible causes: blacks, lifeless after a autopsy & active head turning while laying on back
✖Accidental American period of sleep investigation ✖Avoid maternal & passive smoking
suffocation from soft Indians, & Full cardio- ✖Provide separate sleeping place for infants (No co-sleeping with parent in bed)
bedding Alaska natives respiratory ✖Avoid soft bedding, sheets, & blankets
✖Strangulation Peak incidence arrest & ✖Maintain comfortable room temperature
✖Overlaying by parents occurs at 2-4 unresponsive to ✖Avoid overheating (no heavy blankets or over bundling)
✖Entrapment between mo (uncommon resuscitation. ✖Encourage breast feeding and avoid pacifier during first 3-4sk. Can offer clean
wall and another object. before 2 wks or pacifier after 1 month old if helpful (but to not hang it around infants neck)
after 6 mo) ✖Avoid commercial devices
✖No bumper pads on crib slats
✖Encourage breast feeding