Unique phenotype in a patient with CHARGE syndrome

The CHARGE syndrome (MIM 214800) is an autosomal dominant or sporadic disorder of variable multisystemic congenital anomalies that occurs with an incidence of approximately 1 in 10,000 [1,2]. Heterozygous CHD7 (chromodomain helicase DNA-binding protein 7, MIM 608892) mutations have been identified in approximately 60%-70% of patients with clinically diagnosed CHARGE Syndrome and are most commonly due to de novo truncating mutations. Furthermore, CHD7 mutations are reported throughout the entire coding sequence of the gene without an apparent pattern or cluster, and meaningful genotype-phenotype correlations have not been recognized [1-3].The first descriptions of this syndrome were provided by Hall and Hitner independently in 1979 [4,5], though it was in 1981 that Pagan and colleagues coined the acronym CHARGE to summarize its dominant features: coloboma, heart defects, atresia choanae, retarded growth and development, genital and/or urinary abnormalities, ear anomalies and/or deafness [6]. It was only in 2004 that the CHD7 gene was established as a genetic etiology for CHARGE syndrome by Vissers et al [7]. A wider spectrum of associated features has since emerged, albeit less consistently, and includes hyposmia or anosmia, cleft lip and palate, hypocalcemia [8,9], and tracheoesophageal fistula [10]. As such, CHARGE Syndrome has several overlapping clinical characteristics with DiGeorge syndrome [11], Kallmann syndrome, and Hypoparathyroidism, Sensorineural Deafness, and Renal Disease (HDR) (Barakat's syndrome) [12,13]. As the CHARGE phenotype continues to expand, particularly into the clinical purview of other conditions, its diagnosis becomes more challenging as well as increasingly inclusive.Herein, we report a patient with a unique presentation of CHARGE syndrome, including primary hypoparathyroidism, bilateral multicystic dysplastic kidneys (MCDK), and an atypical limb anomaly; he carried a CHD7 mutation that has not been previously characterized. Our report ex