Board Prep

Genetics
12/2018
GENETICS AND METABOLIC DISORDERS = 3.0%
ABP BREAKDOWN
Question: toxin effects
A 5 year old presents with the following: -shortened palpebral fissures -epicanthal folds -
hypoplastic nasal root -short, upturned nose -hypoplastic philtrum -thin upper lip -midface
hypoplasia -learning problems -weight < 10%ile
What is the most likely diagnosis?
Fetal alcohol syndrome
ANSWER
Fetal Alcohol
Syndrome
To diagnose fetal alcohol syndrome, you must
find abnormalities in each of these 3 areas:
-facial
-pre- or postnatal growth deficiency
-evidence of cognitive abnormality
The facial features commonly are not defined
until 4-8 years of age
Question: toxin effects
WHAT CONGENITAL MALFORMATION DOES CARBAMAZEPINE AND
VALPROIC ACID CAUSE?
Spina bifida
ANSWER
Spina bifida
Use of carbamazepine carries a < 1% risk of spina bifida

Use of valproic acid carries a 2% risk of spina bifida.

Question: toxin effects
ACE INHIBITORS INCREASE THE RISK OF WHAT CONGENITAL ABNORMALITIE S?
NAME ONE.
Renal dysgenesis & oligohydramnios
ANSWER
Renal dysgenesis
&
oligohydramnios
Question: toxin effects
WHAT DOES CIGARET TE SMOKING MOST COMMONLY AFFECT IN
BABIES BORN TO MOTHERS WHO SMOKE?
Weight
ANSWER
Smoking
Low birth weight is the most common manifestation of cigarette smoking in pregnant women.
Smoking can also lead to a higher incidence of miscarriage, prematurity, and stillbirth.
Question: toxin effects
DIETHYLSTILBESTROL (DES) IS ASSOCIATED WITH INCREASING RISK
OF WHICH CANCER IN GIRLS BORN TO MOTHERS ON THIS AGENT?
Vaginal adenocarcinoma
ANSWER
Vaginal
adenocarcinoma
Using DES prior to 12 weeks
gestation results in an increased
risk of vaginal adenocarcinoma in
girls at a later age.
Question: ACRONYMS
WHICH SYNDROME IS CHARACTERIZED BY THESE FINDINGS?
CLEFT PALATE —THYMUS AGENESIS OR HYPOPLASIA —PARATHYROID GLAND
HYPOPLASIA/AGENESIS —TETRALOGY OF FALLOT, INTERRUPTED AORTIC ARCH,
VSD, OR TRUNCUS ARTERIOSUS —SHORT STATURE —BEHAVIORAL PROBLEMS
Renal 22q11.2
ANSWER
Renal 22q11.2
● DiGeorge

● Velocardiofacial syndrome

●CATCH 22
Cardiac defects
Abnormal facies
Thymic hypoplasia
Cleft palate
Hypocalcemia
Question: ACRONYMS
WAGR SYNDROME CONSISTS OF WHICH 4 ABNORMALITIES?
Wilms Tumor
Aniridia
Genitourinary malformation
Mental Retardation, intellectual
disability
ANSWER
WAGR syndrome

results from a deletion of the short

arm of chromosome 11. Wilms
tumor occurs in up to 50% of cases,
most often by 3 years of age. The
GU abnormalities are generally male
genital hypoplasia (hypospadias,
cryptorchidism, etc.)
Question: ACRONYMS
WHAT DOES VACTERL STAND FOR?
Vertebral defects
Anal atresia
Cardiac defects
TracheoEsophageal fistula
Renal malformations
Limb abnormalities (Radial dysplasia)
ANSWER
Vertebral defects
Anal atresia
Cardiac defects
TracheoEsophageal fistula
Renal malformations
Limb abnormalities (Radial dysplasia)
Question: ACRONYMS
WHAT DOES CHARGE SYNDROME STAND FOR?
Coloboma
Congenital heart defects
Choanal atresia
Growth and mental retardation(intellectual
disability)
GU anomalies (hypogonadism)
Ear anomalies

ANSWER
Coloboma
Congenital heart defects
Choanal atresia
Growth and mental retardation
(intellectual disability)
GU anomalies (hypogonadism)
Ear anomalies
Question: ACRONYMS
A NEWBORN PRESENTS WITH THE FOLLOWING: BRANCHIAL CLEFT FISTULAS
OR CYSTS —PREAURICULAR PITS -COCHLEAR AND STAPES MALFORMATION —
HEARING LOSS -RENAL DYSPLASIA/APLASIA
WHAT IS THE MOST LIKELY DIAGNOSIS?
Branchio-Oto-Renal
(BOR) Syndrome
ANSWER
BOR syndrome presents with these findings
and is inherited as an AD disorder.
-branchial cleft fistulas or cysts
-preauricular pits
-cochlear and stapes malformation
-hearing loss
-renal dysplasia/aplasia
Question: DELETION SYNDROMES
YOU DIAGNOSE A CHILD WITH WILLIAMS SYNDROME.
WHAT IS THE MOST LIKELY CARDIAC DEFECT?
Supravalvular aortic stenosis
ANSWER
Supravalvular aortic stenosis

This is the classic cardiac defect

in Williams syndrome.

Know it!
Question: DELETION SYNDROMES
A 4 YEAR OLD PRESENTS WITH THE FOLLOWING: JERKY ATAXIC MOVEMENTS -
HYPOTONIA -FAIR HAIR-MIDFACE HYPOPLASIA -INAPPROPRIATE BOUTS OF
LAUGHTER-SEVERE INTELLECTUAL DISABILITY
WHAT IS THE MOST LIKELY DIAGNOSIS?
Angelman syndrome
ANSWER
Question: DELETION SYNDROMES
A 6 YEAR OLD BOY PRESENTS TO YOU AS A NEW PATIENT WITH THE
FOLLOWING: PERIORBITAL FULLNESS -PROMINENT, DOWN -TURNED LOWER
LIP-A VERY FRIENDLY PERSONALITY -STRABISMUS -INTELLECTUAL DISABILI TY
WHAT IS THE MOST LIKELY DIAGNOSIS?
Williams Syndrome
ANSWER
Williams Syndrome

-due to a microdeletion on the long

arm of chromosome 7

-classically we think of this as the

“cocktail party” personality kid
Question: DELETION SYNDROMES
A 4 YEAR OLD PRESENTS WITH THE FOLLOWING: HISTORY OF SEVERE
HYPOTONIA AT BIRTH -SHORT STATURE -SMALL HANDS AND FEET -
HYPOGONADISM-MILD INTELLECTUAL DISABILITY -OBESITY
WHAT IS THE MOST LIKELY DIAGNOSIS?
Prader-Willi Syndrome
ANSWER
Prader-Willi Syndrome

due to paternally derived

deletion of 15q11-13
Question: DELETION SYNDROMES
A NEWBORN GIRL PRESENTS WITH THE FOLLOWING:OCULAR
HYPERTELORISM -FRONTAL BOSSING -MICROCEPHALY -“BEAKED NOSE” -
HYPTONIA-SEIZURES -PROMINENT GLABELLA
WHAT IS THE MOST LIKELY DIAGNOSIS?
4p-Deletion:
Wolf-Hirschhorn Syndrome
ANSWER
4p-Deletion
Wolf-Hirschhorn Syndrome

The ocular hypertelorism, prominent glabella,

and frontal bossing give the “Greek helmet”
facies that is classic for this disease
Question: AUTOSOMAL DOMINANT DISORDERS
A NEWBORN PRESENTS WITH THE FOLLOWING: INTRAUTERINE GROWTH
RETARDATION -HIRSUTISM -DOWN-TURNED MOUTH-MICROGNATHIA -LOW
HAIRLINE-LONG EYELASHES -THIN UPPER LIP -CARDIAC DEFECTS -MICROMELIA
WHAT IS THE MOST LIKELY DIAGNOSIS?
Cornelia De Lange Syndrome
ANSWER
Cornelia De Lange Syndrome

One of the classic short stature

syndromes

Hirsutism and the micromelia can

help differentiate this from other
disorders
Question: AUTOSOMAL DOMINANT DISORDERS
A YOUNG CHILD PRESENTS WITH: -GENERALIZED OVERGROWTH-MACROGLOSSIA -
POSTERIOR AURICULAR PITS -HISTORY OF OMPHALOCELE -CRYPTORCHIDISM -
HEMIHYPERTROPHY -LGA
WHAT IS THE MOST LIKELY DIAGNOSIS?
Beckwith-Wiedemann Syndrome
ANSWER
Beckwith-Wiedemann
Syndrome

-AD disorder
-Remember that Wilms
tumor is likely in these
children
Question: AUTOSOMAL DOMINANT DISORDERS
A NEWBORN PRESENTS WITH THE FOLLOWING: -DISPROPORTIONATELY SHORT
STATURE WITH RHIZOMELIC SHORTENING -TRIDENT HANDS -MACROCEPHALY -FLAT
NASAL BRIDGE -PROMINENT FOREHEAD -MIDFACIAL HYPOPLASIA
WHAT IS THE MOST LIKELY DIAGNOSIS?
Achondroplasia
ANSWER
Achondroplasia

Most common skeletal dysplasia and occurs in 1/20,0000 live births.

Question: AUTOSOMAL DOMINANT DISORDERS
A NEWBORN PRESENTS WITH THE FOLLOWING: CRANIOSYNOSTOSIS -
BRACHYCEPHALY -HYPERTELORISM -STRABISMUS-MAXILLARY HYPOPLASIA -
NARROW PALATE -SYNDACTYLY (FUSION OF 2, 3 OR 4 FINGERS) -BROAD THUMBS
WHAT IS THE MOST LIKELY DIAGNOSIS?
Apert syndrome
ANSWER
Apert syndrome
Question: AUTOSOMAL DOMINANT DISORDERS
A 1 0 Y E A R O L D P R E S E N T S W I T H O N E O F T H E F O L LO W I N G : E I T H E R 2 O R M O R E
H E M A N G I O B L A S TO M A S I N T H E C E R E B E L LU M O R R E T I N A
O R 1 S I N G L E H E M A N G I O B L A S TO M A W I T H E I T H E R ; - P H E O C H R O M O C Y TO M A - E N D O LY M P H AT I C S A C
T U M O R S - K I D N E Y/ PA N C R E A S C Y S T S - R E N A L C E L L C A R C I N O M A - N E U R O E N D O C R I N E T U M O R S
W H AT I S T H E M O S T L I K E LY D I A G N O S I S ?
Von Hippel-Lindau Syndrome
ANSWER
Von Hippel-Lindau Syndrome

multisystem cancer disorder that presents with

benign and malignant tumors of the eyes, CNS,
kidneys, pancreas, adrenal and reproductive
glands.