Metabolic/Genetics

Question 1

What would be done routinely in a one week old infant with trisomy 21

a. lateral c-spine films
b. abdominal U/s
c. ophthalmology consult – only if cataracts are detected by the red reflex test
d. auditory brain stem response
e. nothing

Answer 1

auditory brain stem

Question 2

An infant is diagnosed to have double outlet right ventricle on echocardiogram. The baby also presents with left eye coloboma and hypertelorism. What is the diagnosis?

a. Alagille Syndrome
b. Noonan’s
c. Williams’ Syndrome -
d. DiGeorge Syndrome

Answer 2

d. DiGeorge Syndrome - usu TGA or truncus, can have

a. Alagille Syndrome - usually PS
b. Noonan’s - usually PS
c. Williams’ Syndrome - supravalvular AS
d. DiGeorge Syndrome - usu TGA or truncus, can have

Question 3

A child presents with a severe metabolic disorder and is extremely unstable. What can you give the child which may give him some benefit while awaiting a diagnosis?

a. D25W
b. carnitine
c. thiamine

Answer 3

carnitine

Question 4

1 week old infant with T21. What should be done prior to discharge home?

a. ABR
b. Ophthalmology consult
c. Abdo U/S
d. Echocardiogram

Answer 4

echo

vs ABR

Question 5

A single umbilical artery is associated with which anomalies

a. Renal anomalies
b. Cardiac
c. pulmonary

Answer 5

renal anomaly

Question 6

1 month old with achondroplasia. What is the MOST important investigation to request at this time? REPEAT
EEG
MRI brain
Xray spine

Answer 6

mri brain
neuroimaging and polysomnography at the time of diagnosis. (AAP GUIDELINES) - can get narrowing of foreaman ovale
proximal bone shortening

Question 7

A 7 year old boy has recent onset hyperactivity and inattention in school. On exam, he also has ataxia. His maternal uncle died at the age of 10 with similar symptoms. What does he have?
Friedrich ataxia
X-linked adrenoleukodystrophy
DMD
Ataxia telangiectasia

Answer 7

XLA
XLadreno - accumulation of saturated VLCFA and progressive dysfunction of adrneal cortex _ central/peripheral WHITE matter
PRESENTATION - 5 types (3 in children)
Childhood cerebral form- 4-8yo, initial presentation hyperactivity, worst school performance, prev well. Auditory discrimination mpaired (ie hard to use phone), spatial orientation affected. Issues with vision, ataxia, poor handwriting, seizures and strabismus. Imapired cortisol response to ACTH (mild hyperpigmentation). Rapid progression, to vegetiation within 1.9 years

Question 8

Child with hemihypertrophy. Other than Wilms tumors, what other neoplasm do you need to screen for:

a) Neuroblastoma
b) Hepatoblastoma
c) No other neoplasms

Answer 8

hepatblastoma

risk of wilm, adrenal carcinoma

Question 9

Baby in the NICU with significant hypotonia, requiring gavage feeding. Puffy hands and feet. What is the most likely diagnosis?
Prader Willi
Turner’s
Trisomy 21

Answer 9

turner
Most common sex chromosome abnormality
Loss of part or all of an X chromosome: 45 XO
Affects approximately 1 in every 2500 liveborn female newborns
Neonates: congenital lymphedema of the hands and feet and two or more of the following dysmorphic features: webbed neck, nail dysplasia, high-arched palate, and short fourth metacarpal
CVS: Abnormalities include aortic valvular disease, aortic arch anomalies (primarily coarctation), systemic venous abnormalities, ventricular septal defects, and hypoplastic left heart syndrome, bicuspid valve MOST common
Patients are at risk for aortic dissection, particularly during pregnancy.

Question 10

A teenage boy has height at 90%, weight at 50%, scoliosis, pectus excavatum, and pes planus. What is the cardiac issue most likely to be seen on his echo?

a. Dilation of aortic root
b. Bicuspid aortic valve - think Turners!
c. Hypertrophic cardiomyopathy
d. Pulmonary stenosis

Answer 10

dilation of aortic root
marfan- autosomal dominant
WITHIN heart - AV valve - thickening and resulting in MVP/TV regurg. With severe MFS insuff MV can lead to CHF, pHTN and daeth
Inc ventricular dysrhtymia, SVT, prolonged QT, dilated cardiomyopathy (low incidence)
OUTSIDE heart - aortic aneurysm and dissection, aortic root dilatation most common

Question 11

A 2yo boy’s weight is at the 99.9th%, length at the 25%. He is hypotonic and is found to have pauses in his breathing when sleeping. Which of the following tests would give the diagnosis?

a. Cytogenetics
b. 7q sequencing
c. karyotype

Answer 11

a. Cytogenetics
IF methylation analysis was an option - pick it for PRADER WILLI

Prader Willi Syndrome UTD
Most common syndromic form of obesity.
Caused by absence of expression of the paternally active genes on the long arm of chromosome 15 (maternal imprinting)
Deletions of PWS-critical region on paternal 15q11-q13 (70%): methylation, FISH, CMA are abnormal
Infants and toddlers: hypotonia and feeding problems, so

Question 12

20 month old M with unusual facies, hypocalcemia, hearing loss. Which of the following is most likely to reveal the diagnosis?

a. FISH for 22q11
b. 7q (William syndrome?)

Answer 12

FISH 22q11
22q11.2 Deletion Syndrome (CATCH 22):
Congenital heart disease (74% of individuals): particularly conotruncal malformations (tetralogy of Fallot, interrupted aortic arch, ventricular septal defect, and truncus arteriosus)
Palatal abnormalities (69%): particularly velopharyngeal incompetence, submucosal cleft palate, bifid uvula, and cleft palate
Characteristic facial features (present in the majority of individuals of northern European heritage)
Learning difficulties (70%-90%)
An immune deficiency (77%): thymic dysplasia
Hypocalcemia (50%)
Significant feeding and swallowing problems; constipation with or without structural gastrointestinal anomalies (intestinal malrotation, imperforate anus, and Hirschsprung disease)
Renal anomalies (31%)
Hearing loss

Question 13

What is not a finding of william

1) 7q11 deletion
2) very friendly/gregarious
3) supravalvular aortic stenosi
4) periorbintal fullness
5) diarrhea

Answer 13

Diarrhea (usually consitpated)

tend to hanve divertilosis

Question 14

You have diagnosed a baby with trisomy 21 at birth. What should be done for the baby at 7 days of life?

a. CBC + smear
b. TSH
c. Eye exam

Answer 14

CBC smear
T21, send FISH (results in 24-48 hours)
If FISH positive, send chromosome analysis for translocations
Discuss and review: hypotonia, facial appearance, feeding issues
Screening:
Echo
Red reflex (cataracts)
Swallowing study (if marked hypotonia or any feeding issues)
CBC (transient myeloproliferative disorder, polycythemia)
TSH (if NBS only includes T4)
Regular newborn hearing testing - have to do oto acoustic AND the automated brainstem reflex (AABR)
Car seat test if hypotonic
Clinical assessment looking for signs/symptoms of associated disease (atresias, anorectal malformations, hirschsprung, GERD, tracheal anomalies

Question 15

In fetal alcohol syndrome, what are the most common cardiac abnormalities seen?

a. Septal defects
b. TGA
c. Bicuspid aortic valve

Answer 15

septal defect
FAS-
prenatal onset and persistence of growth deficiency for length, weight, and head circumference; (2) facial abnormalities, including short palpebral fissures, epicanthal folds, maxillary hypoplasia, micrognathia, smooth philtrum, and a thin, smooth upper lip, (3) cardiac defects, primarily septal defects; (4) minor joint and limb abnormalities, including some restriction of movement and altered palmar crease patterns; and (5) delay of development

Question 16

A 5 month old boy who has been unwell for 48 hours (not feeding, lethargic) presents with glucose 0.8, metabolic acidosis, no urine ketones. Glucagon is given and raises the blood sugar to 1.2. What is the most likely diagnosis?

a. Glycogen storage disease (have ketoneS)
b. Fatty acid oxidation disorder
c. Hyperinsulinism (usu present at neonatal, have ketones)

Answer 16

FAOD

HALLMARK OF FAOD = absence of ketones during fasting

Question 17

An infant is diagnosed to have double outlet right ventricle on echocardiogram. The baby also presents with left eye coloboma and hypertelorism. What is the diagnosis?

a. Alagille Syndrome - usually PS
b. Noonan’s - usually PS
c. Williams’ Syndrome - supravalvular AS
d. DiGeorge Syndrome - usu TGA or truncus, can have

Answer 17

digeorge syndrome - usu TGA or truncus

Question 18

9 month old with irritability. Has had microcephaly since birth, also has bitemporal narrowing, bilateral epicanthal folds, thin upper lip, cleft palate, 2-3 toe syndactyly

a) Fetal alcohol syndrome
b) Angelman
c) Smith-Lemli-Opitz
d) Trisomy 18

Answer 18

c) Smith-Lemli-Opitz
congenital multiple anomaly syndrome caused by an abnormality in cholesterol metabolism, narrow forehead
- cleft palate, cardiac defects, underdeveloped external genitalia in males, postaxial polydactyly, and 2-3 syndactyly of the toes

Trisomy 18 - would see microcephaly, low set eats, short sternum,

Question 19

Myotonic infant with fasiculations, low reflexes. Parents wonder chance of recurrence?

a) 25% recur
b) 50%
c) 50% males
d) Sporadic

Answer 19

25% recur

SMA? = AR in most cases

Question 20

V-shaped upper lip and myotonic girl, how do you get the diagnosis?

Answer 20

a) DNA
Genetic testing needed
Myotonic Dystrophy:
DM1: expansion of a CTG trinucleotide repeat in the 3’-untranslated region of the dystrophia myotonica protein kinase gene (DMPK gene) on chromosome 19q13.3
DM2: expanded CCTG tetranucleotide repeat expansion located in intron 1 of the zinc finger protein 9 gene (ZNF9 gene, also known as the CNBP gene) on chromosome 3q 21.3

Question 21

Kid ravenous, growing well, hugging you, but not receptive to caregiver

a) Diencephalic syndrome
b) Neglect

Answer 21

neglect

Question 22

Fatty Acid Oxidation Defect. What is the most common presentation

a) Intractable Seizures (usually 2ndary to hypoglycemia)
b) Coma

Answer 22

COMA
FAO
Mitochondrial fatty acid oxidation plays an important role in energy production, particularly during fasting
May present with lethargy and encephalopathy during times of decreased carbohydrate intake or fasting
Hepatomegaly is sometimes present.
Biochemical features of fatty acid oxidation disorders include hypoglycemia with inappropriately absent ketosis and liver dysfunction

Question 23

3 year old Girl with developmental regression and small head

a) Rett

Answer 23

rett syndrome
Main criteria for RTT are as follows UTD- X linked AD (mecp2) - most commonly sporadic mutation, usually INHERITED from PATERNAL, which is F>M, look normal upto 1 yr
●Partial or complete loss of acquired purposeful hand skills
●Partial or complete loss of acquired spoken language
●Gait abnormalities: impaired (dyspraxic) or absence of ability
●Stereotypic hand movements such as hand wringing/squeezing, clapping/tapping, mouthing, and washing/rubbing automatisms

Question 24

6 wk old male presents with poor feeding and hypotonia. on physical exam you note that he has difficulties sucking and swallowing and has fasciculations and decreased deep tendon reflexes. what would be the most diagnostic test?
MRI
thyroid function
metabolic screen
genetic testing

Answer 24

genetic testing

SMA pg 2136 nelson - definitive diagnosis is molecular genetic marker in blood for SMN gene

Question 25

A dad has Hemophilia A. The mom is a carrier. If they have a daughter, what are the chances she will have Hemophilia A disease?
0%
25%
50%
100%

Answer 25

50%

Question 26

A dad has Hemophilia A. The mom is a carrier. If they have a daughter, what are the chances she will have Hemophilia A disease?
0%
25%
50%
100%

Answer 26

50%

Hemophilia = X-linked recessive

Question 27

You are following a newborn with Trisomy 21. What investigation should you do on an annual basis?
Xray of c-spine
TSH
Celiac screen
Sleep study

Answer 27

TSH
T21 Health Supervision
Thyroid: repeat measurement of TSH at 6 and 12 months of age and then annually
OSA: discuss symptoms with parents. If symptomatic → refer
C-spine: only if symptomatic (see below), by 2 age
Celiac: only if symptomatic
Hemoglobin concentration beginning at 1 year of age and annually thereafter.

Question 28

A 5 year old child presents lethargic and unwell looking, labs show a metabolic acidosis with Hyponatremia, Hyperkalemia and hypoglycemic. Which of the following would confirm the diagnosis?
Serum cortisol
acyl carnitine profile (fatty oxidation and aminoacidopathy)

Answer 28

serum cortisol

Adrenal crisis in infants and older children previously diagnosed with adrenal insufficiency presents with weight loss, serum electrolyte abnormalities (including hyponatremia and hyperkalemia).

Question 29

A 2 week old baby’s newborn screen came back positive for Carnitine Palmitoyltransferase II Deficiency. What is the best course of action until results are confirmed?
Start PO Carnitine
Feed frequently (Q3H)
Amino Acid formula
Hypercalori formula

Answer 29

feed frequently 3QH
Since it is not a primary Carnitine deficiency, giving carnitine (substrate) will not work!

Fatty acid transport defect - disrupt the carnitine cycle, which shuttles long-chain fatty acids from the cytosol into the mitochondrial matrix where fatty acid oxidation occurs. Treatment is mainly dietary: high carbohydrate, low fat + protein, frequent meals. Avoid prolonged fasting or aerobic exercise >30 mins, carb load prior to exercise.

Question 30

A newborn baby is found to have choanal atresia. What other findings would be consistent with this?
Heart and Coloboma
Anal and spine abnormalities
neural tube defects

Answer 30

heart and coloboma
Neonates require immediate evaluation of the airway, feeding, heart, and hearing.

CHARGE
Association - two or more anomalies that are not pathogenetically related and occur together more frequently than expected by chance
Syndrome - pattern of anomalies that occur together and are pathogenetically related (mutation in CHD7 = autosomal dominant)
Coloboma + anopthalmia, micropthalmia, hypertelorism
Heart: Tetralogy of Fallot, ASD, VSD, double outlet RV, PDA, PV stenosis
Atresia (choanal): unilateral/bilateral or stenosis
Retardation of mental and somatic development
Genital: microphallus, cryptorchidism
Ear abnormalities and/or deafness : small or cup-shaped ears, SNHL or mixed
Other: growth deficiency (70%-80%), orofacial clefts (15%-20%), TEF (15%-20%)

Question 31

A newborn has choanal atresia – what other features do you look for?
Keyhole pupil and murmur
Failure to pass orogastric tube & imperforate anus
Omphalocele and cleft palate
Wide spaced nipples & webbed neck

Answer 31

keyhole pupil and murmur

Question 32

An infant is diagnosed antenatally with a cardiac rhabdomyoma. What is the most likely diagnosis?
NF1
TS
WAGR
Beckwith Weidemann

Answer 32

TS
Tuberous Sclerosis UTD
Inherited neurocutaneous disorder: characterized by pleomorphic features involving many organ systems
autosomal dominant genetic disorder with an incidence of approximately 1 in 5000 to 10,000 live births
TSC1 gene or the TSC2 gene
De novo mutations account for approximately 80 percent of TSC cases
Most infants and children who have cardiac rhabdomyomas have TSC