Table 3.

Bardet-Biedl Syndrome: Genes and Distinguishing Clinical Features

Gene 1
(BBS Designation 2)		% of all
BBS 3		Distinguishing Clinical Features / CommentsAllelic Disorder(s) 4
BBIP1
(BBS18)		<1%Reported in 2 unrelated persons w/multiple major features of BBS but w/o polydactyly 5None
BBS1 23.4%
  • Relatively less "syndromic" 6 w/↓ penetrance of renal anomalies & polydactyly
  • Founder variant in Newfoundland population 7
BBS2 9.6% Nonsyndromic retinitis pigmentosa
BBS4 5.3%
  • ↓ penetrance of renal anomalies
  • Early-onset morbid obesity
None
BBS5 3.7%Relatively more "syndromic"
BBS7 4.2%Relatively more "syndromic" w/↑ penetrance of renal anomalies
BBS9 3.4%↑ penetrance of renal anomalies
TTC8
(BBS8)		2.0%Relatively less "syndromic" w/↓ penetrance of renal anomalies Nonsyndromic retinitis pigmentosa
ARL6
(BBS3)		5.1%
  • Least "syndromic" w/low penetrance of cognitive impairment & renal anomalies
  • Polydactyly often affects all 4 limbs.
  • Founder variant in population on La Réunion Island 8
BBS10 14.5%
  • Most severe renal impairment
  • Significant adiposity
  • Founder variant in South African population 9
None
BBS12 6.4%Significant adiposity
MKKS
(BBS6)		6.3%More likely to have CHD & genitourinary malformationsMcKusick-Kaufman syndrome 10
CFAP418
(formerly known as C8orf37)
(BBS21)		1.6%↑ penetrance of polydactyly
CEP164 <1%Reported in 1 person suspected of having PCD due to unexplained cough & bronchiectasis, but reverse phenotyping revealed features of BBS 11 Isolated nephronophthisis
CEP290
(BBS14)		6.3%Significant clinical overlap w/other ciliopathies See footnote 10.
IFT27
(BBS19)		<1%
  • Reported in 3 persons from 2 families, all w/major features of BBS
  • 1 person w/AVCD 12
None
IFT74
(BBS20) 13		<1%
  • Reported in 2 unrelated persons; both w/retinal disease, obesity, polydactyly, & no renal involvement
  • 1 person w/ID 14
IFT172
(BBS20) 13		1.0%Typical BBS features
LZTFL1
(BBS17)		<1%
  • Reported in 3 persons from 2 families
  • Mesoaxial-type polydactyly a unique feature 15
None
MKS1
(BBS13)		1.0%Ophthalmology exam may show bone-spicule hyperpigmentation & attenuated arteries. 16
SCAPER UnknownLinkage & functional studies in 2 consanguineous families w/multiple persons w/features of BBS support causation. 17ID disorder & retinitis pigmentosa (OMIM 618195)
SCLT1 <1%Reported in 4 persons from 2 families:
  • In 1 family, affected persons have pituitary hypoplasia & growth hormone deficiency + obesity, retinal disease, & polydactyly.
  • In the other family, affected persons have major features of BBS. 18
Possible assoc between variation in SCLT1 & orofacial digital syndrome IX (OMIM 258865)
SDCCAG8
(BBS16)		4.3%Intronic variants reported 11Senior-Løken syndrome 10 (OMIM 613615)
TRIM32
(BBS11)		<1%Identified in a consanguineous Bedouin family 19Limb-girdle muscular dystrophy (OMIM 254110)
WDPCP
(BBS15)		<1%Reported in 2 unrelated persons w/BBS (clinical data unavailable) 20CHDs, hamartomas of tongue, & polysyndactyly (OMIM 217085)

AVCD = atrioventricular canal defect; BBS = Bardet-Biedl syndrome; CHD = congenital heart defect; ID = intellectual disability; PCD = primary ciliary dyskinesia

1.

Genes are listed in alphabetic order.

2.

Included when BBS designation differs from gene

3.

Determined by data of 923 individuals with BBS (899 from a meta-analysis of genotype-phenotype associations by [Niederlova et al 2019], 17 from a report by [Shamseldin et al 2020] not included in the meta-analysis, and 7 from additional case reports supporting causation of rare genes).

4.

Link to OMIM gene description provided if no GeneReview available

5.
6.

Use of the word "syndromic" refers to syndromic score used by Niederlova et al [2019] calculated as number of major features present in an individual divided by five (all major features excluding reproductive system anomalies [excluded due to differences in male and female physiology]).

7.
8.
9.
10.

These disorders have phenotypic overlap with BBS and should be considered in the differential diagnosis of BBS (see Table 2).

11.
12.
13.

In the literature, both IFT74 and IFT172 are associated with BBS20, so the recommendation is to discard the use of "BBS20."

14.
15.
16.
17.
18.
19.
20.

From: Bardet-Biedl Syndrome Overview

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