23 Syndromic Diseases with Cardiac Involvement



10.1055/b-0035-121518

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

Syndrome


Characteristics


Associated heart defects


Remark


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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