20
General Principles
Table 9. Genetic Syndromes and Their Associations With
Congenital Heart Disease
Syndrome
Genetic
Abnormality Clinical Features
22q11.2 deletion
syndrome (DiGeorge
syndrome,
velocardiofacial
syndrome)
22q11.2 deletion Facial dysmorphia, palate and speech
abnormalities, thymic and parathyroid
hypoplasia, hypocalcemia, immunodeficiency,
neurodevelopmental and psychiatric disorders
Down syndrome Trisomy 21 Facial dysmorphia, developmental
disability, atlantoaxial instability,
obstructive sleep apnea, craniofacial
abnormalities
Holt-Oram syndrome TBX5 Upper-limb skeletal abnormalities,
conduction abnormalities
Klinefelter syndrome 47, XXY Tall stature, hypoplastic testes, delayed
puberty and developmental disability
Noonan syndrome PTPN11, KRAS,
SOS1, RAF1,
NRAS, BRAF,
MAP2K1
Facial anomalies, webbed neck, chest
deformity, lymphatic abnormalities,
bleeding abnormalities
Turner syndrome 45, X Short stature, webbed neck, lymphedema,
primary amenorrhea
Williams syndrome 7q11.23 deletion "Elfin" facial features, social personality,
hearing loss, developmental delay, infantile
hypercalcemia
Alagille syndrome JAG1 Facial dysmorphism, hepatic dysfunction
(chronic cholestasis, elevated liver enzymes,
biliary atresia, hypercholesterolemia, or
liver failure), neurovascular accidents, renal
anomalies (renal artery stenosis, hypertension,
renal tubular acidosis, uteropelvic obstruction,
small, hyperechoic kidneys)
Heterotaxy syndrome ZIC3,
SHROOM3,
GRK 5, ANKS3,
NODAL,
CFC1, LEFTY2,
GDF1, SMAD2,
ACVR2B
Situs abnormalities, ciliary dysfunction,
functional asplenia, conduction
abnormalities, biliary atresia
Modified with permission from Stout et al. Copyright © 2018 American Heart Association, Inc.
and American College of Cardiology Foundation.
