AREDYLD syndrome with focal segmental glomerulosclerosis

Abstract

The syndrome of AcroRenal-Ectodermal Dysplasia-Lipoatrophic Diabetes (AREDYLD) appears to be extremely rare with only 2 cases reported. A third patient, described here, presented in her early 30's with infertility, lipoatrophy of the face, diabetes, hypercholesterolemia, and nephrotic syndrome. Renal biopsy showed focal segmental glomerulosclerosis. She has normal areolae, but no breast tissue. Other ectodermal features are milder than in previous patients (slow-growing hair, but no significant anomalies of the teeth or nails). Despite normal menses and structurally normal internal genitalia, she has been unable to conceive. She has short stature, small acrogeric hands and feet and microcephaly, but her intelligence is above average. She is an only child with no affected relatives. Her karyotype is normal, 46XX.This patient has symptomatic progressive glomerular disease of adult onset whereas the previous patients had minor structural anomalies of the renal calyces. Although her renal disease is more severe, she is not more seriously affected otherwise since her ectodermal involvement is mild and her diabetes is of later onset.The phenotype of AREDYLD now appears to include: a variety of renal anomalies ranging from minor malformations to glomerular disease; minor anomalies of the hands and feet; amastia or breast hypoplasia with or without other ectodermal anomalies (such as sparse hair, hypodontia, hypohidrosis or nail dysplasia); lipoatrophy, primarily involving the face and hands; diabetes; and hypercholesterolemia. Three cases have been reported, all in females. Autosomal recessive inheritance has been postulated because the first reported patient was born to consanguineous parents and had a possibly affected deceased sister, but autosomal or sex-linked dominant cannot be excluded.