Differential Diagnosis
Bardet-Biedl syndrome (BBS) is a multisystem non-motile ciliopathy primarily characterized by retinal rod-cone dystrophy, truncal obesity and related complications, postaxial polydactyly, cognitive impairment, hypogonadotropic hypogonadism and/or genitourinary malformations, and renal malformations and/or renal parenchymal disease (for overview, see Bardet-Biedl Syndrome Overview). Overlap with MKS occurs due to the finding of HMC (in females), genital malformations in males, and postaxial polydactyly and congenital heart disease in both conditions. At least 26 genes are known to be associated with BBS. Pathogenic variants in MKKS account for an estimated 6.3% of all BBS (see BBS Overview). The genital malformations associated with MKS, including HMC, vaginal atresia, and cryptorchidism, have also been associated with BBS-related genes including BBS2, BBS6, BBS10, and BBS12, suggesting that these features are not MKKS/BBS6 specific . Note: Although several reports have described BBS phenotypes with three pathogenic variants and at least one variant involving the MKKS locus , triallelic inheritance has been refuted in other studies and is not currently considered a typical inheritance pattern for either MKS or BBS . illustrates the phenotypic overlap between MKS and BBS (+ = major feature; ± = minor feature). Table 3. Phenotypic Overlap Between McKusick-Kaufman Syndrome and Bardet-Biedl Syndrome
Clinical Feature | MKS | BBS |
|---|
Hydrometrocolpos in females | + | ± |
Congenital heart disease | + | ± |
Polydactyly | + | + Retinitis pigmentosa |
Source: GeneReviews — "McKusick-Kaufman Syndrome"
