Lymphedema, Cardiac Septal Defects, And Characteristic Facies

Clinical Features

Irons et al. (1996) reported 2 brothers with lymphedema of the lower limbs, hydrocele, atrial septal defects (ASD), epicanthus, and wide nasal bridge. Their stillborn sister, who was born after a pregnancy complicated by preeclampsia, had severe hydrops fetalis, omphalocele, ASD, and polysplenia. The family history was unremarkable. Irons et al. (1996) considered this complex to be a previously unknown syndrome with autosomal recessive inheritance.

Van Steensel et al. (2007) described a 3-year-old Dutch girl with features similar to those in the patients reported by Irons et al. (1996). She was born prematurely at 35 weeks with a dizygotic twin sister. The parents were nonconsanguineous and 3 sibs were healthy. During pregnancy, fetal hydrops was detected from weeks 16 to 20. At birth, she was noted to have bilateral swelling of the lower legs consistent with lymphedema. She also had atrial flutter, a large perimembranous ventricular septal defect with significant left/right shunting, a secundum type atrial septal defect type II, and an overriding aorta with vascular ring. At age 2 months, the ventricular septal defect was closed, the vascular ring corrected, and an aortopexia was performed. Progressive bilateral lower leg lymphedema was noted at 3 years of age. Physical examination at that time revealed nonpitting edema of the toes, feet, and lower legs. Her face showed epicanthal folds, flat nasal bridge with telecanthus, and a high forehead. Lymphoscintigraphy revealed complete absence of lymph drainage in both lower legs. Karyotype was normal 46,XX, and a 22q11 deletion was excluded by FISH. Analysis of several genes known to be involved in syndromes with lymphedema detected no pathogenic mutations.

Levine and Echiverri (2009) reported a 22-year-old African American man with mild mental retardation, mild dysmorphic features, history of a congenital atrial septal defect, massive lymphedema of the lower limbs, and hydrocele. Dysmorphic features included prominent forehead, bitemporal narrowing, epicanthal folds, hypertelorism, and flat and wide nasal bridge. Levine and Echiverri (2009) noted that the patient resembled the brothers reported by Irons et al. (1996), although their patient did not have deep-set nails or a horizontal chin cleft, and had more severe cognitive impairment.