Pediatric Boards Genetics And Metabolic Disorders

Front 1

Suspect congenital anomalies if >3 minor or 1 major. What are the major and minor anomalies?

Back 1

Minor: 2-3 toe syndactyly, hypertelorism (eyes far apart), preauricular ear tag, epicanthal folds
Major: cleft lip/palate, CHD, brain anomalies, omphalocele, limb absence

Front 2

What diseases are children with trisomy 21 at risk for?

Back 2

CHD, duodenal atresia, leukemia, Hirschprung's disease, MR. Hypotonia is one of the most common abnormalities in babies who have DS, occurring in up to 90%.

Front 3

Rocker bottom feet, hand clenching-chromosomal abnormality?

Back 3

Edward's syndrome (trisomy 18) Usually fatal in first year of life. 95% spontaneously lost before delivery.

Front 4

Clef palate, holoprosencephaly, chromosomal abnormality?

Back 4

Patau syndrome (trisomy 13), clinically severe, usually death in first year of life, 20% of cases are due to unbalanced translocation (parents have inc recurrence risk).

Front 5

Mom's risk of having another child with chromosomal abnormality?

Back 5

1% added to mom's maternal age risk.

Front 6

Nuchal webbing, puffy hands/feet (pedal edema), CHD (coarctation), short stature, no periods/infertile (gonadal dysplasia?

Back 6

Turner syndrome (45, X). This is the one of the only chromosomal abnormalities not related to maternal age.

Front 7

Tall stature, small testes, gynecomastia, learning/behavioral problems?

Back 7

Klinefelter (47, XXY). Can have more than 2 X chromosome-increased risk for neuro issues.

Front 8

What study looks for microdeletion syndromes?

Back 8

FISH

Front 9

What does CATCH 22 stand for?

Back 9

cardiac defects/conotruncal, abnormal facies, T cell deficit, cleft palate, hypocalcemia


22q Microdeletion syndrome/DeGeorge/Velocardiofacial

CHD and MR-think about this deletion, can also be missing thymus

Front 10

Shrill cry, low broad nose, hypertelorism (not necessarily distinct characteristic features?

Back 10

5p- syndrom/Cri du chat (deletion of short arm of chromosome 5), most are sporadic but 10-15% are due to translocation

Front 11

Greek helmet appearance (middle part of nose pushed forward)?

Back 11

4p-/Wolf-Hirschhorn Syndrome)

Front 12

What does WAGR stand for?

Back 12

Wilms tumor, Aniridia (absence of the iris), GU anomalies, mental Retardation.
Chromosomal deletion syndrome, AD

Front 13

Male to male transmission (excludes all x linked and mitochondrial transmission), both sexes are equally affected, in every generation, 50% chance of giving it to their offspring

Back 13

AD

Front 14

Diagnostic criteria for Marfan syndrome?

Back 14

AD, 25% due to new mutation
-Skeletal changes (tall/thin, scoliosis, pectus deformities, long fingers)
-Eyes (myopia, dislocated lens**)
-Heart (aortic dilation**, dissections)
-Not common-learning disorders

If no family hx-major criteria in at least 2 organ systems and invovlement of third system.
If positive family hx-one major criteria in at least 1 organ system and involvement of second system

Front 15

Paucity of bile ducts, triangular face?

Back 15

Alagille syndrome. AD
-Paucity of bile ducts, cardiac defects (PS), eye anomalies, butterfly vertebrae

Front 16

Achondroplasia-what is inheritance pattern?

Back 16

AD, 80% new mutations, more severe if get 2 mutations

Front 17

What is CHARGE syndrome?

Back 17

AD, generally sporadic

C-coloboma/CNS dz
H-heart defects-
A-choanal Atresia
R-retardation of growth
G-GU anomalies
E-ear anomalies or deafness

Front 18

Osteogenesis imperfecta

Back 18

AD
-See osteopenia, multiple fracture, blue/grey sclera, dental abnormalities, hearing loss, short stature

Front 19

AR

Back 19

-2 mutatant alleles for the same gene, males and females equally affected, 25% recurrent risk of parents of affected, an unaffected sibling has a 2/3 chance of being a carrier, consanguinity increases the rsk

Front 20

Examples of AR conditions

Back 20

CF, hemoglobinopathies, metabolic conditions

Front 21

X linked inheritance

Back 21

-50% chance of females transmitting to sons, no male to male transmission, all daughters of affected males are obligate carriers, males severely affected

Front 22

Examples of X linked disorders?

Back 22

Duchenne Muscular dystrophy/DMD
Incontinentia Pigmenti (X linked dominant, see females with dz, men tend to die as fetuses)
G6PD deficiency
Rett syndrome (x linked dominant as well, females develop normally and then drop off, microcephaly)
Alport syndrome (women have milder dz, kidney failure/deafness/abnormal eye exam)
Aicardi syndrome

Front 23

Peg shaped teeth,linear blistering rash (no erythema) that scabs?

Back 23

Incontinentia pigmenti

Front 24

What diseases can result from 15q11-13 chromosome deletion?

Back 24

Prader Willi syndrome-from the dad's side
Angelman syndrome-from the mom's side

Front 25

Angelman syndrome

Back 25

Severe MR, ataxic gait with jerky arm movements, seizure EEg abnormalities, inappropriate laughter, blond hair/blue eyes

Front 26

Prader Willi syndrome

Back 26

Hypotonic infant, FTT/difficulty feeding infant. Then at 2-4 years of age begans rapidly eating--see obesity, small hands/feet, short stature, hypogonadism

Front 27

Beckwith-Wiedemann syndrome

Back 27

Macroglossia, ear lob pits/creases, macrosomia, hemihypertrophy, omphalocele, risk for embryonal tumors, imprinting vs AD

Front 28

Fragile X

Back 28

-Trinucleotide repeat expansion (size of repeat correlates with severity and age of onset)
-Increasing # of repeats in successive generation-anticipation
-Most common inherited form of MR (most common chromosomal cause is Down's)
-MR, large ears, generalized overgrowth

Front 29

Risk of multifactorial inheritance to siblings (ie cleft lip/palate)?

Back 29

2-6%

Front 30

Cornelia de Lange syndrome

Back 30

AD, Poor growth, IUGR, skeletal/limb abnormalities, short upturned nose, unibrow

Front 31

Noonan syndrome

Back 31

AD, short stature, hypertelorism, low set ears, lymphedema, delayed puberty/ cryptochordism, heart defects (pulmonary valve stenosis), normal intelligence

Front 32

Williams syndrome

Back 32

microdeletion (FISH), short stature/FTT, short nose, puffy eyelids, full mouth into a big smile!, MR, behavioral phenotype (talk a lot without saying anything), supravalvular aortic stenosis (get test for syndrome if has this)

Front 33

Most common cause of bone marrow failure, abnormal thumbs/radial defects?

Back 33

Fanconi Anemia, AR, chromosomal instability

See pancytopenia (fatigue, frequent infections, easy bruising), inc risk of AML, other physical abnormalities including cafe-au-lait spots, heart, ears, eyes and GU system.

Front 34

Ehlers Danlos syndrome

Back 34

AD, connective tissue disorder, hypermobility form is most common, classic form = stretchy skin

Front 35

VATER/VACTERL

Back 35

Vertebral abnormality
Anal atresia
Cardiac
TE fisulta
Esophageal atresia
Renal anomalies
Limb anomalies

Front 36

Syndromes with severe neurological manifestations?

Back 36

Meckel Gruber Sx (lethal)
Angelman/Prader Willi Sx
Walker-Warburg Sx
Sturge Weber sx
Rett Sx (pictured above)

Front 37

SYndromes with thumb/radi defects and Hematological abnormalities?

Back 37

Fanconi anemia (pancytopenai, hypoplastic thumb and radius, hyperpigmentation)
Diamond BlackFan Anemia (radial hypoplasia, anemia, CHD)
Thrombocytopenia-absent radius syndrome (no radii, normal thumbs, low platelets/petechiae)
Hold-Oram sx

Front 38

Syndromes with growth abnormalities?

Back 38

Prader Willi
Angelmann Sx
Sotos Sx
Beckwith-Wiedemann sx
Proteus sx

Front 39

Syndromes with short stature

Back 39

Cornelia de lange
Dubowitz sx
Noonan sx
Williams sx

Front 40

The combination of tetralogy of Fallot, hypoplastic thumbs, cleft palate, and a renal abnormality described for the infant in the vignette is highly suspicious for?

Back 40

22q11 deletion syndrome

Front 41

Treacher Colin Syndrome

Back 41

TCS is an autosomal dominant condition that is highly variable and is caused by spontaneous gene mutations in 60% of affected individuals. Unusual features associated with TCS include downslanting eyes with lower lid coloboma (notching) and absent eyelashes medial to the notch, malar hypoplasia, hypoplastic/malformed external ears with conductive and/or sensorineural hearing loss, and microretrognathia that has the potential to compromise the airway.

Front 42

Most metabolic disorders are what type of inheritance?

Back 42

AR

Exceptions: Hunter's sx (X linked), mitochondrial disorders, OtC (x linked)

Front 43

Most common disorder of amino acid metabolism? Inc frequency in Irish descent?

Back 43

PKU, phenylalanine is not broken down, normal at birth but severe damage by 8 weeks of age.

Presentation: seizures, autism, musty odor. Goal is to start treatment by 2 weeks of age.

Dx: Elevated plasma phenylalanine level, on all newborn screens (no TPN), low plasma tyrosine level

TX: low phenylalanine intake

Front 44

Abnormal metabolism of methionine?

Back 44

Homocystinuria
Clinical features: marfanoid habitus, DD, gross motor delays, ataxia. Increase in homocysteine and methionine
Tx: Pyridoxine

Front 45

Succinylacetone buildup is cause of symptoms in this amino acid disorder?

Back 45

Tyrosinemia Type 1

Front 46

In utero hiccups, neonate presents with seizures and apnea?

Back 46

Nonketotic Hyperglycinemia-glycine encephalopathy.
Dx by comparing CSF and plasma glycine levels.

Front 47

Hyperammonemia, increased glutamine, no ketoacidosis, respiratory alkalosis, mild or no liver dysfunction?

Back 47

Urea cycle defect disorders. High ammonia is what causes symptoms. Start seeing CNS symptoms around 100-200. No Ketones in the urine (unlike organic acid syndromes)

-CPS1 (normal/low orotic acid)
-NAG (normal/low orotic acid)
-OTC deficiency (X linked, elevated orotic acid)
-Citrullinemia (high citrulline, normal orotic acid)
-Argininosuccinic Aciduria/ASA (hair thing-trichorrhexis nodosa, high citrulline, high ASA)
-Arginase deficiency (only one that does not present with high ammonia-->spastic quadriplegia, ataxia)

Front 48

How do you treat urea cycle disorders?

Back 48

Give Phenylbutyrate, arginine or citrulline; protein restriction; and increase caloric intake; use HD for hyperammonemia if necessary

Front 49

High anion gap, metabolic acidois, ketonuria-what type of metabolic disorders?

Back 49

Organic Acidurias. Buildup of ketoacids. Have elevated urine organic acids, hypoglycemia
TX: low protein diet, extra biotin and carnitine

Front 50

Organic Aciduria disorder (with elevated valine, isoleucine, leucine and alloisoleucine in plasma and urine?

Back 50

Maple Syrup Urine disease.
Presents with CNS disease, normal baby who deteriorates at 3-4 days of life, feeding difficulties, irregular respirations, loss of Moro reflex. Abnormal odor of "maple syrup"
-inc frequency in Mennonites

Front 51

Organic Aciduria commonly precipitated by infection, can also see osteoporosis?

Back 51

MMA and propioic acidemia.

Propionic: ketotic hyperglycemia, AG metabolic acidosis, hyperammonemia, thrombocytopenia

Front 52

Liver disease, jaundice, cataracts, E Coli sepis, presents with vomiting and diarrhea?

Back 52

Galactosemia-deficiency in GALT.
Dx-NbS, positive urine reducing substances
Tx: Soy formula

Front 53

Presents at about 6 month of age (with fruit/fruit juices), jaundice, abnormal LFTs, severe hypoglycemia?

Back 53

Hereditary fructose intolerance/HFI.
Inc incidence in Europe.

Front 54

FTT, low blood sugar, lactic acidosis, hypotonia, myopathy?

Back 54

Fatty Acid Oxidation defects.
Dx difficult (some on Nbs). May require skin/muscle biopsy.
Cannot fast as fatty acid oxidation is responsible for energy during fasting.
Get hypoketotic hypoglycemia, acidosis, hepatomegaly. Low glucose can be a late finding.

Front 55

Most common form of fatty acid oxidation defect?

Back 55

MCAD, Presents in first 2 years of life, stress/fasting can induce illness. Can cause SIDS.
FTT, low blood sugar, lactic acidosis, hypotonia, myopathy, cannot fast! low ketones
Tx: frequent feedings, carnitine

Other types: VLCAD, LCHAD, SCAD

Front 56

Problems manifest during fasting. See hypoglycemia, hepatomegaly, protuberant abdomen, inc LFTs, increased ketones, "doll like facies,?

Back 56

Glycogen Storage Disease. Defect in G6P in liver, kidney and intestine. Cannot convert glycogen to glucose.
Dx: Gene analysis
TX: Cornstarch, allopurinol

Front 57

Muscle cramps with exercise in young adults/teens, urine turns brown (myoglobinuria), elevated CK levels even at rest, elevated lipids, second wind phenomenon?

Back 57

GSD V/McArdle's disease.

Front 58

Glycogen accumulates in the lysosomes -either presents in an infant with cardiomegaly or later on in life as a myopathy?

Back 58

GSD Type 2/Pompe's disease (lysosomal storage disease)

Front 59

Accumulation of sulfate presents with regressive development, dsymorphic syndromes, bone dysplasia or learning/developmental issues?

Back 59

MPS/Mucopolysaccharidoses
Coarse facies, distinctive bone changes, joint stiffness, macrocephaly, hernias, corneal clouding. Examples include Hurler syndrome (AR). Hunter's syndrome (no vision problems/corneal clouding, X linked). Development for many children with an MPS disorder is initially normal, subsequently plateaus, and then regresses because of accumulation of metabolic by-products (glycosaminoglycans). Diagnostic screening includes urine testing for glycosaminoglycans and definitive testing for specific enzymes, depending on the findings on the urine test

Front 60

Common in Ashkenazi's Jewish population, cherry red spot, progressive CNS deterioration?

Back 60

Tay-Sach's disease (sphingolipioses)

Front 61

Erlenmeyer flask deformation fracture, hepatosplenomegaly, thrombocytopenia, anemia, pain crises, can have normal development?

Back 61

Gaucher's disease.
-Can present like leukemia with pancytopenia, organomegaly, FTT, and bone pain. Dx with glucocerebrosidase assay

Front 62

Peroxisomal disorder. Zellweger syndrome.

Back 62

Patients can show craniofacial abnormalities (such as a high forehead, hypoplastic supraorbital ridges, epicanthal folds, midface hypoplasia, and a large fontanel), hepatomegaly (enlarged liver), chondrodysplasia punctata (punctate calcification of the cartilage in specific regions of the body), eye abnormalities, and renal cysts.[5] Newborns may present with profound hypotonia (low muscle tone), seizures, apnea, and an inability to eat