Genetic Syndrome Associations

Question 1

What cardiac abnormality is associated with William’s syndrome?

Answer 1

Supravalvular aortic stenosis

Can also see pulmonary stenosis

Question 2

What is the cardiac abnormality associated with DiGeorge Syndrome?

Answer 2

• Most common cardiac finding is a VSD with other common findings including right sided aortic arch, conotruncal heart defects (including TOF most commonly but any cardiac outflow tract disorders), and aberrant subclavian arteries

Question 3

What is the cardiac abnormality associated with Down Syndrome?

Answer 3

Most common cardiac lesions are endocardial cushion defects (ASD, VSD and AVSD*)
Can also have PDA, aberrant subclavian arteries, and pulmonary hypertension, mitral/aortic/tricuspid valve regurg

Question 4

What is the cardiac abnormality associated with Turner’s Syndrome?

Answer 4

Most common cardiac anomaly is bicuspid aortic valve
Can also have coarctation of the aorta, cardiac conduction abnormalities, hypoplastic left-heart syndrome and other left-heart abnormalities, and aortic dissection later in life

Question 5

What is PHACES Syndrome?

Answer 5

Posterior fossa malformation
Hemangiomas- large segmental facial lesions
Arterial abnormalities
Cardiac abnormalities- especially coarctation
Eye abnormalities
Sternal cleft

Question 6

What is the inheritance of SMA?

Answer 6

Autosomal Recessive

Question 7

What is the inheritance of DiGeorge Syndrome?

Answer 7

93% denovo mutations

AD inheritance of these mutations - in future generations

Question 8

What are the clinical features of DiGeorge Syndrome?

Answer 8

CATCH-22 *deletion of 22q11 
Cardiac- VSD, conotruncal abnormalities 
Abornmal facies- tubular nose
Thymic hypoplasia- T cell abnormalities- wait to given live vaccines
Cleft palate 
Hypocalcemia

Question 9

What are the clinical features of McCune Albright Syndrome?

Answer 9

McCune-Albright Syndrome:
Syndrome of endocrine dysfunction associated with patchy cutaneous pigmentation and fibrous dysplasia of the skeletal system
Rare condition; classic cause of peripheral precocious puberty
Features include:
Precocious puberty→ predominantly in girls
Hyperthyroidism with multinodular goiters
Cushing syndrome may also occur – low ACTH, adrenal function not suppressed by exogenous steroids, may require adrenalectomy
Increased GH occurs uncommonly
Geographical hypopigmentation that respects the midline

Question 10

What are clinical features of Klinefelter’s Syndrome?

Answer 10

“Male Turner’s Syndrome”
47 XXY
1 in 600 males
Puberty often begins at appropriate age, penile enlargement and pubic hair
Key finding is disproportionately small, firm testes, gynecomastia, infertility
Increased learning and behavioral difficulties

Question 11

What are clinical features of Turner’s Syndrome?

Answer 11

Turner Syndrome
Karyotype range from complete 45 XO to forms of mosaicism (eg 45 X,46 XX)
1 in 2000 live female births
Mean adult height (untreated) 144 cm
Growth hormone improves height
Gonadal failure 96%, infertility 99%

Question 12

Which syndrome is associated with hypercalcemia in the neonatal period in 10% of children?

Answer 12

William’s Syndrome

Question 13

What are features of Noonan’s Syndrome?

Answer 13

Previous known as pseudo-Turner’s Syndrome
Hypertelorism, blue eyes, downward slanting palpebral fissures, webbed neck, pectus excavatum, may have delayed puberty (cryptoorchidism, small penis)
May have lymphedema of the hands and feet
Heme- may have coagulopathy

Question 14

What are features of CHARGE syndrome?

Answer 14

Coloboma of the eye +/- microphthalmia
Heart defects- conotruncal abnormalities; arch abnormalities
Atresia- choanal atresia*
Retardation of growth
GU/GI- microphallus and other abnormalities
Ears- malformed helix, deafness; extremities- club foot, absent tibia

Question 15

What are features of VACTERL?

Answer 15

Vertrebral abnormalities
Anal atresia
Cardiac defects
Tracheoesophageal defects
Renal abnormalities
Limb abnormalities 

*denovo mutations

Question 16

How is the diagnosis of Tuberous Sclerosis Complex made? What are the major and minor criteria?

Answer 16

Need 2 MAJOR or 1 MAJOR and 2 MINOR

Major Cx: 
Cortical tuber 
Subependymal nodule 
Subependymal giant cell astrocytoma 
Facial angiofibroma or forehead plaque 
Ungal or periungal fibroma
Hypomelanotic macules (>3- Ash leaf spots)
Shagreen Patch 
Multiple retinal hamartomas 
Cardiac rhabdomyoma 
Renal angiomylolipoma 

Minor Cx:
Multiple dental pits, gingival fibromas, bone cysts, confetti skin lesions, non-renal hamartomas, multiple renal cysts

Question 17

What is TSC associated with?

Answer 17

Polycystic Kidney Disease

Question 18

What are examples of imprinting disorders?

Answer 18

Prader Willi Syndrome
Angelman Syndrome
Russel Silver Syndrome
Beckwith Weidman Syndrome

Question 19

What is the most commonly inherited disorder of congenital pancytopenias?

Answer 19

Fanconi Anemia

Question 20

What are features of Fanconi anemia?

Answer 20

Abnormal thumbs- bifid, supernumerary, or absent
Absent radius
Hypopigmented lesions
Short stature
Will develop marrow failure within the first decade of life

Question 21

What is the most common inherited cause of intellectual disability?

Answer 21

Fragile X

Question 22

A baby has a direct hyperbilirubinemia. He was treated for an E. coli sepsis. He has hepatomegaly on exam. Which test will likely yield the diagnosis?

Answer 22

GALT

• E Coli Sepsis should raise concern for galactosemia which is a deficiency in GALT enzyme
• Screened for on NBS
• Autosomal recessive inheritance

Question 23

What are four long term complications to monitor for in Williams Syndrome?

Answer 23

ECHO- supravalvular aortic stenosis
Thyroid function- hypothyrodism
Ophtho- catarcts
Learning assessment- intellectual disability 
Nephrocalcinosis

Question 24

How is the diagnosis of Galactossemia suggested? How is it confirmed?

Answer 24

Urine reducing substances

GALT assay