Cardiovascular malformations in Fryns Syndrome: Is there a pathogenic role for Neural Crest cells?

ArticleinAmerican Journal of Medical Genetics Part A 139(3):186-93 · December 2005with8 Reads
Impact Factor: 2.16 · DOI: 10.1002/ajmg.a.31023 · Source: PubMed

    Abstract

    We performed a comprehensive literature and case report review to characterize the cardiovascular malformations (CVMs) associated with Fryns syndrome (OMIM #229850), a multiple congenital anomaly/mental retardation syndrome consisting of diaphragmatic defects, significant pulmonary hypoplasia, distinctive facial appearance, distal digital hypoplasia, and numerous other external and internal anomalies. A total of 112 patients meeting diagnostic guidelines for Fryns syndrome were identified, of whom 82 met narrowly defined criteria (Group 1) and 30 met broader diagnostic criteria (Group 11). Twelve patients reported as having Fryns syndrome with atypical features (Group 111) were also analyzed. A CVM was reported in 51% (42 of 82) of Group I patients, most commonly an atrial or ventricular septal defect (VSD) (23 of 42, 55%). Conotruncal and aortic arch CVMs were common (11 of 42,26%), but not significantly so compared to the general population of infants to age 1 year [Ferencz et al., 1997]. Recognizing that minor septal defects associated with congenital diaphragmatic hernia (CDH) may occur in response to altered hemodynamics (instead of being a bonafide CVM), we excluded four patients reported as having hemo-dynamically insignificant VSDs. Following these exclusions, conotruncal CVMs were found more commonly than in the general population (11 of 38, 29%, P <= 0.025). In Group II, 9 of 30 (30%) had a CVM with no predominant type among the small number of cases reviewed. Among the atypical Fryns syndrome patients in Group 111, half (6 of 12, 50%) had a CVM; most (4 of 6, 67%) were conotruncal, in particular, type B interrupted aortic arch (3 of 4). Patients with Fryns syndrome have a high rate of CVMs, warranting thorough cardiac evaluation including echocardiogram (fetal and/ or postnatal) in all patients, similar to the evaluation for other patients with diaphragmatic hernia.