Table 2.

Disorders to Consider in the Differential Diagnosis of Bardet-Biedl Syndrome

Gene(s) 1DisorderMOIClinical Features of the Differential Disorder
Overlapping w/BBSDistinguishing from BBS
ALMS1 Alström syndrome (AS)AR
  • Cone-rod dystrophy (presents earlier in AS)
  • Central obesity, insulin resistance / T2DM, & NAFLD
  • Chronic progressive kidney disease
  • Hypogonadism
In AS:
  • Preserved cognitive function; cardiomyopathy prevalent (in ~60%); symptomatic progressive SNHL; pulmonary fibrosis & pulmonary hypertension
  • Absence of polydactyly
MKKS McKusick-Kaufman syndrome (MKS)AR
  • Postaxial polydactyly
  • Genitourinary malformations
In MKS:
  • Congenital heart disease more prevalent (in ~14%); hydrometrocolpos a cardinal feature; renal cysts/dysplasia less common (in 4%-6%)
  • Absence of retinal disease, obesity, & developmental disabilities
~15 genes 2Meckel syndromeAR
  • Postaxial polydactyly
  • Polycystic kidney disease
  • Genitourinary malformations
  • Hepatic fibrosis
Meckel syndrome:
  • Occipital encephalocele & other CNS anomalies cardinal features; orofacial clefting common
  • Perinatally lethal
AHI1
CC2D2A
CEP290
CPLANE1
MKS1
NPHP1
TMEM67
(>36 genes)		Joubert syndrome (JS)AR
XL 3
  • Retinal degeneration
  • Polydactyly
  • Kidney & liver disease
In JS:
  • Characteristic triad of molar tooth sign on brain MRI, hypotonia, & DD; breathing abnormalities that improve w/age common; eye mvmt abnormalities &/or ptosis common
  • Central obesity, hypogonadism, & genitourinary malformations are atypical.
CEP290
IQCB1
NPHP1
NPHP4
SDCCAG8
TRAF3IP1
WDR19 		Senior-Løken syndrome (SLS) (OMIM PS266900)AR
  • Retinal degeneration
  • Kidney disease
Absence of obesity, polydactyly, hypogonadism, & genitourinary malformations in SLS
CEP290
CRB1
GUCY2D
RDH12
RPE65
(~25 genes)		Leber congenital amaurosis / early-onset severe retinal dystrophy (LCA/EOSRD)AR
AD		Retinal degeneration & assoc symptoms (e.g., ↓ visual acuity)Absence of other organ involvement in LCA/EOSRD

AD = autosomal dominant; AR = autosomal recessive; CNS = central nervous system; DD = developmental delay; MOI = mode of inheritance; NAFLD = nonalcoholic fatty liver disease; SNHL = sensorineural hearing loss; T2DM = type 2 diabetes mellitus; XL = X-linked

1.

Pathogenic variants in bolded genes are also known to cause BBS.

2.

See Phenotypic Series: Meckel Syndrome to view genes associated with this phenotype in OMIM.

3.

Digenic inheritance has been reported.

From: Bardet-Biedl Syndrome Overview

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