23 Syndromic Diseases with Cardiac Involvement


23 Syndromic Diseases with Cardiac Involvement

23.1 Overview of Syndromic Diseases with Cardiac Involvement

An overview of the most common syndromic diseases associated with congenital heart defects is presented in Table 23.1. Marfan and Marfanlike syndromes are discussed separately in Chapter 23.2.

Table 23.1 Overview of the most common syndromic diseases associated with congenital heart defects



Associated heart defects


Trisomy 21 (Down syndrome)

Short stature, generalized muscle hypotonia, simian crease, sandal gap (large distance between the 1st and 2nd toes), clinodactyly of the 5th finger, brachycephalus with mongoloid eye slant, epicanthus, macroglossia, Brushfield spots, psychomotor retardation, average IQ of 50 (considerable variation), pancreas annulare, Hirschsprung disease

AVSD, VSD, Fallot tetralogy, PDA, rarely coarctation of the aorta, aortic stenosis

Most common chromosomal abnormality with an incidence of 1:650 of all live births; the incidence increases with maternal age. Approximately 40–50% of children have a heart defect, approximately half of these have AVSD

Trisomy 18 (Edwards syndrome)

Intrauterine growth retardation, short trunk, small nipples, microcephaly, craniofacial anomalies (prominent occiput, low-set ears, small mouth, micrognathia), renal anomalies. Typical hand position: flexion of the fingers where the index finger and little finger are bent over the middle and ring fingers

VSD (almost always present, often as malalignment VSD), cardiac valvulopathy (“polyvalvular disease,” such as thickened leaflets, long chordae, hypoplastic or absent papillary muscles), DORV, Fallot tetralogy

Second most common chromosomal abnormality with an incidence of 1:3,500 of all live births. The prognosis is poor. Most children die within the first weeks of life, only 10% survive the first year. Survival into adulthood has been described in some cases, but severe mental retardation is always present

Trisomy 13 (Patau syndrome)

Microcephaly, scalp defects, microphthalmia, coloboma, cleft lip and palate, flexion contractures of the fingers, rocker bottom feet, polydactyly, renal anomalies, mental retardation

PDA, VSD, ASD, valvular anomalies, coarctation of the aorta

Incidence 1:4000–10,000 of all live births. Cardiac defects occur in 80%, the majority of those affected have complex cardiac defects. The prognosis is as poor as that of trisomy 18, the mortality rate in the first year of life is 80–90%

Trisomy/tetrasomy 22p (“cat-eye” syndrome)

Mild mental retardation, hypertelorism, iris coloboma, ear tags, kidney dysplasia (large variability of the phenotype)

Anomalous pulmonary venous connections, Fallot tetralogy, VSD, left persistent superior vena cava, interrupted inferior vena cava, tricuspid atresia

Cardiac defects occur in 40% of patients

Turner syndrome (45, X0)

Congenital lymphedema (almost pathognomonic), short stature, pterygium colli, short fingers, widely spaced nipples, ovarian dysgenesis, renal anomalies

Coarctation of the aorta, bicuspid aortic valve, aortic stenosis, hypoplastic left heart syndrome, aortic dilation, aortic dissection

Incidence 1:2,500 of all female newborns. Cardiac defects occur in 20–40% of patients, usually obstruction or hypoplasia of the left heart. The spectrum ranges from asymptomatic bicuspid aortic valve up to hypoplastic left heart syndrome. The most common is coarctation of the aorta

Noonan syndrome

Short stature, pterygium colli, chest deformities, congenital lymphedema, cryptorchismus, mental retardation (usually mild)

Myxomatous valvular pulmonary stenosis, hypertrophic cardiomyopathy, ASD, VSD

Affected genes: mostly PTPN11 mutation, rarely KRAS, SOS1, autosomal dominant inheritance. The phenotype is similar to Turner syndrome

Microdeletion 22q11 (DiGeorge syndrome, velo-cardio-facial syndrome, Shprintzen syndrome, “conotruncal anomaly face” CATCH 22)

Cardiac anomalies, abnormal facies, thymus hypoplasia, cleft palate, hypocalcemia, mental retardation of varying degrees. Pronounced genotype-phenotype variability

Interrupted aortic arch, truncus arteriosus communis, Fallot tetralogy, pulmonary atresia with VSD, VSD, aortic arch anomalies

Incidence 1:5,000 of all live births. Malformation of the 3rd/4th pharyngeal pouch. The great variability of expression is reflected in the different names of the syndrome, all of which are now summarized as microdeletion 22q11. Cardiac defects occur in approximately 80% of patients. Typical defects are conotruncal anomalies, i.e., heart defects affecting mainly the great vessels.

Patients with 22q11 microdeletion should always be examined for immune defects

Holt–Oram syndrome

Malformations of the upper extremities

ASD, VSD, anomalous pulmonary venous connection, conduction disturbances

Affected gene: TBX5, autosomal dominant inheritance, cardiac anomalies occur in about 75% of patients, an ASD is typical

Alagille syndrome

Intrahepatic cholestasis (biliary atresia), typical face (prominent forehead and chin, deep-set eyes, and anomalies of the anterior chamber [posterior embryotoxon]), butterfly vertebrae

Peripheral pulmonary stenosis, Fallot tetralogy, valvular pulmonary stenosis, ASD, VSD

Affected genes: JAG1, NOTCH2, autosomal dominant inheritance, cardiac defects occur in approximately 90% of patients, peripheral pulmonary stenosis is typical

Ellis–van Creveld syndrome

(chondroectodermal dysplasia)

Short stature, short limbs, ectodermal dysplasia (hypoplastic nails, dental abnormalities), polydactyly, narrow thorax, usually normal intelligence

Common atrium, ASD I, AVSD

Affected gene: EVC, autosomal recessive inheritance. Cardiac defects occur in approximately 50% of cases, anomalies that affect the embryonic AV channel are typical

Williams–Beuren syndrome

(“elfin face” syndrome)

Short stature, mental retardation, elflike facies with midface hypoplasia, hypodontia, very good verbal skills, friendly behavior, sometimes social disinhibition, hoarse voice, hypercalcemia, hypogenitalism, early tendency to arterial hypertension

Supravalvular aortic stenosis, (peripheral) pulmonary stenosis, coarctation of the aorta, coronary artery stenosis, renal artery stenosis

Incidence 1:10,000–20,000 of all live births. Affected gene: elastin gene (ELN1), microdeletion 7q11.2. Cardiac defects occur in approximately 75% of cases. Supravalvular aortic stenosis is typical, less often peripheral pulmonary stenosis, coarctation of the aorta, and stenosis of the peripheral arteries

VATER association (VACTERL association)

Combination of vertebral, anorectal, cardiac, tracheo-esophageal (tracheal fistulas), esophageal (esophageal atresia), renal, and limb anomalies, intrauterine growth retardation

Broad range of cardiac anomalies, most common are VSD, single umbilical artery

Incidence 1:6,000 of all live births, mostly sporadic occurrence, cardiac defects are present in approximately 50% of the cases

CHARGE association

Coloboma, cardiac anomalies, choanal atresia, retarded development, genital hypoplasia, ear anomalies

Conotruncal anomalies (Fallot tetralogy, DORV, truncus arteriosus communis), aortic arch anomalies (vascular rings, arteria lusoria, interrupted aortic arch)

Affected genes: CHD7, SEMA3E. Cardiac defects are present in approximately 70% of cases, conotruncal and aortic arch anomalies are typical

LEOPARD Syndrome

Lentiginosis (pigmentation of the skin), ECG changes, ocular anomalies, pulmonary stenosis, genital anomalies, retardation, deafness

Valvular pulmonary stenosis, hypertrophic cardiomyopathy, conduction disorders

Affected gene: PTPN11. Cardiac defects are present in more than 70% of cases, valvular pulmonary stenosis is typical

Smith–Lemli–Opitz syndrome

Syndactyly of the 2nd and 3rd toes, short stature, microcephaly, genital anomalies

ASD, VSD, AVSD, anomalous pulmonary venous connection

Incidence 1:20,000 of all live births, affected gene DHCR7, autosomal recessive inheritance

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Jun 13, 2020 | Posted by in CARDIOLOGY | Comments Off on 23 Syndromic Diseases with Cardiac Involvement

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