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A 2-year-old presents with an atrial septal defect (ASD). Her mother also had an ASD that was closed with device closure. Her grandfather also had an ASD and has a pacemaker due to complete atrioventricular (AV) block. Of the following, which pathogenic mutation is most likely associated with this finding?


B. NKX2.5

C. NF1



Answer: B

Mutations in NKX2.5 are associated with ASDs and progressively disrupt electrical conduction and can progress to complete heart block. Over time, the specialized conduction cells in the AV node are lost and replaced by fibrotic tissue, resulting in progressive defects in electrical conduction. This patient should be monitored for AV block in the long term due to the strong family history of both ASD and conduction abnormalities.

NOTCH1 mutations in humans cause bicuspid aortic valves. Neurofibromatosis is associated with thickened valves and is caused by mutation of the NF1 gene. TBX5 is associated with Holt-Oram syndrome. Although patients with the Holt-Oram syndrome can have ASDs, progressive conduction problems would be unexpected. JAG1, a NOTCH ligand, can cause outflow tract defects associated with the autosomal dominant disease Alagille syndrome.

A newborn has hypotonia, dysmorphic features (see figure below), and a murmur. What chromosomal abnormality and form of congenital heart disease best fits these exam findings?


(Reproduced, with permission, from Rudolph CD, Rudolph AM, Lister GE, First LR, Gershon AA. Rudolph’s Pediatrics. 22nd ed. New York: McGraw-Hill, 2011.)


A. Trisomy 13: ventricular septal defect (VSD)

B. Trisomy 21: complete atrioventricular (AV) canal defect

C. Microdeletion 7q11: supravalvular aortic stenosis

D. Microdeletion 22q11: tetralogy of Fallot

E. Trisomy 18: VSD

Answer: B

This child’s features are most consistent with Down syndrome, or trisomy 21. The prevalence of congenital heart defect (CHD) in this population is approximately 40% to 50%. Complete AV septal defect (AVSD; also termed endocardial cushion defect or AV canal defect) accounts for 40% of all CHDs in Down syndrome patients, and this figure increases to almost 60% when partial AVSD (primum ASD and inlet or canal-type VSD) is included.

The American Academy of Pediatrics recommends routine echocardiographic screening of neonates with Down syndrome to facilitate ...

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