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Bardet-Biedl Syndrome

Synonym: Biedl-Bardet Syndrome

, MBBS, BMedSci, MRCPCH and , BSc, MD, FRCP, FMedSci.

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Initial Posting: ; Last Revision: April 23, 2015.

Estimated reading time: 52 minutes


Clinical characteristics.

Bardet-Biedl syndrome (BBS) is characterized by rod-cone dystrophy, truncal obesity, postaxial polydactyly, cognitive impairment, male hypogonadotropic hypogonadism, complex female genitourinary malformations, and renal abnormalities. The visual prognosis for children with BBS is poor. Night blindness is usually evident by age seven to eight years; the mean age of legal blindness is 15.5 years. Birth weight is usually normal, but significant weight gain begins within the first year and becomes a lifelong issue for most individuals. A majority of individuals have significant learning difficulties; a minority have severe impairment on IQ testing. Renal disease is a major cause of morbidity and mortality.


The diagnosis of BBS is established by clinical findings. At least 19 genes are associated with BBS: BBS1, BBS2, ARL6 (BBS3), BBS4, BBS5, MKKS (BBS6), BBS7, TTC8 (BBS8), BBS9, BBS10, TRIM32 (BBS11), BBS12, MKS1 (BBS13), CEP290 (BBS14), WDPCP (BBS15), SDCCAG8 (BBS16), LZTFL1 (BBS17), BBIP1 (BBS18), and IFT27 (BBS19).


Treatment of manifestations: Visual aids and educational programs for the visually impaired. Obesity is managed with diet, exercise, and behavioral therapies; hypercholesterolemia and diabetes mellitus are treated as in the general population. Early intervention and special education address cognitive disability; speech therapy for speech delay/impairment. Renal anomalies and hypertension are treated as in the general population; renal transplantation has been successful. Hydrocolpos, vaginal atresia, or hypospadias may be surgically corrected. Hormone replacement therapy for hypogonadism. Cardiac abnormalities are treated as in the general population. Surgery to remove accessory digits prevents functional interference and poor fitting of footwear.

Prevention of secondary complications: Antibiotic prophylaxis for surgical and dental procedures is indicated for individuals with structural cardiac anomalies.

Surveillance: Regular ophthalmologic evaluation, monitoring of renal function, endocrine and lipid profile, and annual blood pressure measurement.

Agents/circumstances to avoid: Any substances contraindicated in persons with renal impairment.

Pregnancy management: Expectant mothers affected with BBS require close monitoring for any deterioration in renal function or pregnancy-related complications due to structural abnormalities of the reproductive tract.

Genetic counseling.

BBS is typically inherited in an autosomal recessive manner. Both interfamilial and intrafamilial phenotypic variability exists. In some families, pathogenic variants in more than one BBS locus may result in a clinical phenotype of BBS. However, such families are difficult to identify and by previous estimations may account for less than 10% of all BBS. It is thus prudent to use the following autosomal recessive risk figures when providing genetic counseling: at conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing is possible if the pathogenic variants in a family are known. Prenatal diagnosis using second-trimester ultrasound examination to detect anomalies associated with BBS such as postaxial polydactyly and renal cysts has been reported. Once the pathogenic variants have been identified in the family, prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis are possible.


Clinical Diagnosis

The diagnosis of Bardet-Biedl syndrome (BBS) is established by clinical findings. Beales et al [1999] and Beales et al [2001] have suggested that the presence of four primary features or three primary features plus two secondary features is diagnostic. See Forsythe & Beales [2013], Table 1.

Note: Establishing the diagnosis of BBS in a given individual may be delayed as a result of the slow emergence and variable expression of the clinical features [Beales et al 1999]. Difficulties in diagnosis arise, for example, in an obese child with learning difficulties and developmental delay but without polydactyly. Until he or she develops visual disturbance, the differential diagnosis is broad.

Primary Features

Rod-cone dystrophy. Atypical pigmentary retinal dystrophy with early macular involvement is the characteristic fundus abnormality in BBS and is called rod-cone dystrophy (see Retinitis Pigmentosa) [Héon et al 2005, Azari et al 2006]. It is often the diagnostic handle that prompts investigation for BBS and it is present in more than 90% of individuals [Forsythe & Beales 2013]. Visual acuity (central retinal function mediated by cones), dark adaptation, and peripheral visual fields (peripheral retina function mediated by rods) are affected.

Postaxial polydactyly. Polydactyly may involve either all four limbs (21% of cases) or the hands or feet alone. Typically, additional digits are found on the ulnar side of the hand and on the fibular side of the foot.

Truncal obesity. Obesity is reported to occur in 72%-92% of affected individuals [Forsythe & Beales 2013] .The mean body mass index (BMI) in females is estimated to be 31.5 mg/m2 while in males it is 36.6 mg/m2 [Moore et al 2005].

Learning disabilities. See Clinical Description, Cognitive impairment.

Hypogonadism (in males) or genital abnormalities (in females). Of 105 affected individuals from a multiethnic cohort, 59% had genital abnormalities [Deveault et al 2011].

  • Males. Small penile shaft and/or reduced volume of testes. Cryptorchidism has been reported in 9% of males [Beales et al 1999].
  • Females. Hypoplastic fallopian tubes, uterus, and ovaries; partial and complete vaginal atresia; septate vagina; duplex uterus; hydrocolpos, hydrometrocolpos; persistent urogenital sinus; vesico-vaginal fistula; absent vaginal orifice; and absent urethral orifice have been reported [Mehrotra et al 1997, Uğuralp et al 2003].

Renal anomalies. Renal malformations and abnormal renal function leading to end-stage renal disease (ESRD) can be a major cause of morbidity and is present in 53%-82% of affected individuals [Imhoff et al 2011, Forsythe & Beales 2013]. Renal manifestations include renal dysplasia characterized by malformation of the renal parenchyma and cystic tubular disease (e.g., nephronophthisis) which often presents with anemia, polyuria, and polydipsia in late childhood. Less frequently, glomerular disease, which on occasion presents with focal segmental glomerulosclerosis and histopathologic splitting of the glomerular basement membrane, has been reported [François et al 1987, Barakat et al 1990]. Many affected individuals have urinary concentrating defects even in the absence of major structural abnormalities and presence of near-normal renal function [Marion et al 2011]. Lower urinary tract malformations such as detrusor instability of the bladder occur, but are less common than upper-tract malformations [Beales et al 1999].

Secondary Features

Speech delay/disorder. In BBS establishment of intelligible speech is often delayed until age four years; however, disordered speech (e.g., phonation difficulties such as breathy, high-pitched speech) has been reported infrequently in BBS [Beales et al 1999]. It has been suggested that substitutions of consonants at the beginning of words and the omission of the final consonant are distinctive of BBS [Beales et al 1999]. Videofluoroscopy and palatal articulation studies point to incoordination of the pharyngeal and/or laryngeal muscles as the possible basis of the problem.

Developmental delay. Many children with BBS are delayed in reaching major developmental milestones including gross motor skills, fine motor skills, and psychosocial skills (interactive play/ability to recognize social cues) [Beales et al 1999].

Behavioral abnormalities. Described in about 33% of individuals with BBS, behavioral abnormalities include emotional immaturity, outbursts, disinhibition, depression, lack of social dominance, and obsessive compulsive behavior [Beales et al 1999].

Eye abnormalities include strabismus, cataracts, and astigmatism.

Brachydactyly/syndactyly. Brachydactyly of both the hands and feet is common as is partial syndactyly (usually between the 2nd and 3rd toes) [Beales et al 1999]. Formal measurement of digit length and width and comparison with normalized charts may be helpful in assessing brachydactyly.

Ataxia/poor coordination/imbalance. Many affected individuals describe a degree of clumsiness and often have a wide-based gait. Tandem walking (in a straight line with one toe abutting the other heel) is usually impossible. Repetitive supination and pronation of the hands at the wrist is slow (dysdiadochokinesia) [Beales et al 1999]. Despite occasional reports of cerebellar involvement, there is no indication that cerebellar function is abnormal. More likely, a yet-to-be-delineated defect in coordination and processing movements exists. It is not known when these features become evident.

Mild hypertonia (especially lower limbs). It is not known when this becomes evident [Beales et al 1999].

Diabetes mellitus. Diabetes mellitus tends to become evident in adolescence or adulthood. It is usually non-insulin dependent diabetes mellitus (NIDDM)/type 2 diabetes mellitus [Beales et al 1999], although occasionally insulin is required for acute control of hyperglycemia. Diabetes mellitus may relate to the level of obesity and one study reports a frequency of 6% in individuals with BBS [Imhoff et al 2011]. Impaired glucose tolerance has been described in younger individuals prior to the onset of NIDDM [Green et al 1989].

Orodental abnormalities include dental crowding, hypodontia, small dental roots, and high-arched palate [Beales et al 1999].

Cardiovascular anomalies. Echocardiographic studies of 22 individuals with Bardet-Biedl syndrome revealed cardiac abnormalities in 50% [Elbedour et al 1994]. The study of Beales et al [1999] identified congenital heart disease in approximately 7% of affected individuals that was equally divided between aortic stenosis, patent ductus arteriosis, and unspecified cardiomyopathy. Valvular stenoses and atrial/ventricular septal defects are the most commonly reported lesions [Beales et al 1999, Slavotinek & Biesecker 2000].

Hepatic involvement. Perilobular fibrosis, periportal fibrosis with small bile ducts, bile duct proliferation with cystic dilatation, biliary cirrhosis, portal hypertension, and congenital cystic dilations of both the intrahepatic and extrahepatic biliary tract have been described [Baker & Beales 2009].

Craniofacial dysmorphism. Craniofacial defects include brachycephaly, macrocephaly, narrow forehead, male frontal balding, large ears, short and narrow palpebral fissures, a long smoothphiltrum, depressed nasal bridge, short nose with reduced bulbosity at the nasal tip, relative upward displacement of the nose and upper lip, midface retrusion, and mild retrognathia [Beales et al 1999, Lorda-Sanchez et al 2001, Moore et al 2005, Tobin et al 2008]. Dysmorphic features are inconsistently present and can be subtle (see Figure 1) [Forsythe & Beales 2013].

Figure 1.

Figure 1.

Images of affected individuals demonstrating the dysmorphic features associated with BBS a-d. Typical facial features; these are often subtle and are not always present. Features include deeply set eyes, widely spaced eyes, downslanted palpebral fissures, (more...)

Hirschsprung disease (absence of enteric nerves in the distal colon). The incidence of Hirschsprung disease in BBS is unknown [Beales et al 1999, Tobin et al 2008]. (See Hirschsprung Disease Overview.)

Anosmia. Partial or complete anosmia has been described following initial observations in mouse models of the condition [Kulaga et al 2004, Nishimura et al 2004, Fath et al 2005, Iannaccone et al 2005]. It remains to be seen whether a relatively simple smell identification test is of diagnostic value.

Molecular Genetic Testing


  • Pathogenic variants in 14 genes are known to be associated with BBS: BBS1, BBS2, ARL6 (BBS3), BBS4, BBS5, MKKS (BBS6), BBS7, TTC8 (BBS8), BBS9, BBS10, TRIM32 (BBS11), BBS12, MKS1 (BBS13), and CEP290 (BBS14) (see Table 1a and Table 1b).
  • Pathogenic variants in five additional genes – WDPCP (BBS15), SDCCAG8 (BBS16), LZTFL1 (BBS17), BBIP1 (BBS18), and IFT27 (BBS19) – may be associated with BBS based on the evidence for these genes (see Table 1b and Molecular Genetics).

Evidence for additional locus heterogeneity. Approximately 20% of persons with BBS do not have identifiable pathogenic variants in any of the 19 known BBS-related genes; therefore, it is possible that more BBS-related genes are yet to be identified.

Table 1a.

Molecular Genetics of Bardet-Biedl Syndrome (BBS): Most Common Genetic Causes

Gene 1, 2Locus Name% of BBS Attributed to Pathogenic Variants in This GeneProportion of Pathogenic Variants 3 Detected by Test Method
Sequence analysis 4Gene-targeted deletion/duplication analysis 5
BBS1BBS1~23.2% 6All variants reported to dateUnknown, none reported 7
BBS10BBS10~20% 8All variants reported to dateUnknown, none reported 7
BBS2BBS2~8.1% 6All variants reported to dateUnknown
BBS9BBS9~6.0% 95 of 7 reported pathogenic variantsExon or whole-gene deletions (2 of 7 reported pathogenic variants)
MKKSBBS6~5.8% 6All variants reported to dateUnknown, none reported 7
BBS12BBS12~5% 10All variants reported to dateUnknown, none reported 7
MKS1BBS13~4.5% 11All variants reported to dateUnknown, none reported 7
BBS4BBS42.3%All variants reported to date(Multi)exon deletions
BBS7BBS7~1.5% 63 of 4 reported pathogenic variants(Multi)exon deletions (1 of 4 reported pathogenic variants)
TTC8BBS8~1.2% 6All variants reported to dateUnknown, none reported 7

Pathogenic variants of any one of the genes included in this table account for ≥1% of BBS.


Genes are listed from most frequent to least frequent genetic cause of BBS.


See Molecular Genetics for information on pathogenic variants detected.


Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.


Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods that may be used can include: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single exon deletions or duplications.


No deletions or duplications involving these genes as causative of Bardet-Biedl syndrome have been reported. The clinical usefulness of such tests is unknown.


Table 1b.

Molecular Genetics of Bardet-Biedl Syndrome (BBS): Less Common Genetic Causes

Gene 1, 2Locus NameReference
ARL6BBS3Katsanis [2004]
BBIP1BBS18Scheidecker et al [2014]
BBS5BBS5Katsanis [2004]
CEP290BBS14Stoetzel et al [2007]
IFT27BBS19Aldahmesh et al [2014]
LZTFL1BBS17Marion et al [2012]
SDCCAG8BBS16Otto et al [2010]
TRIM32BBS11Chiang et al [2006]
WDPCPBBS15Kim et al [2010]

Pathogenic variants of any one of the genes listed in this table is reported in only a few families (i.e., <1% of BBS).


Genes are listed in alphabetic order.


Testing Strategy

To confirm/establish the diagnosis in a proband

  • The diagnosis of BBS relies on clinical findings and family history.
  • Molecular genetic testing using clinically available tests can be used to confirm the diagnosis.
  • Multigene panels offer the most effective approach in achieving molecular confirmation of BBS. Different laboratories offer varying multigene panels and can confirm their local variant detection rate. Genotype-phenotype correlations are unclear; thus, there is no recommended strategy for single gene testing. In this instance it is prudent to sequence the genes that are most commonly mutated (in persons of northern European origin these include BBS1 and BBS10).
    For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.

Clinical Characteristics

Clinical Description

A wide range of clinical variability is observed within and among families with Bardet-Biedl syndrome (BBS) [Baker & Beales 2009]. The main clinical features are cone-rod dystrophy, with childhood-onset vision loss preceded by night blindness; postaxial polydactyly; truncal obesity that manifests during infancy and remains problematic throughout adulthood; intellectual disability; male hypogenitalism and complex female genitourinary malformations; and renal dysfunction, which is a major cause of morbidity and mortality.

Rod-cone dystrophy. Occurring in more than 90% of individuals with BBS, retinitis pigmentosa often begins in childhood. During infancy optic disks and retinal vessels are normal; maculopathy associated with disk pallor develops in late childhood. The earliest signs of retinal dysfunction may not be apparent until age seven to eight years, when night blindness insidiously ensues [Beales et al 1999]. Marked phenotypic variation can occur: maculopathy may be associated with or without peripheral retinal degeneration [Héon et al 2005, Azari et al 2006]. The vascular attenuation which may accompany changes in the macula may be severe.

Visual fields are usually abnormal by age ten years. During adolescence visual field loss is moderate to severe with a reported annual loss of up to three degrees per year. Typically little more than a central island of vision remains by age 17 years.

By the second to third decade of life, the macula is involved in all individuals and is accompanied by visual acuity of 20/200 or worse. Legal blindness affects about 75% of affected individuals. In a previous study 63.6% of affected individuals were legally blind by age 20 years [Klein & Ammann 1969].

Full-field rod and cone electroretinograms (ERGs) are the investigations of choice to document the retinal involvement. ERG findings often include severely reduced or extinguished responses with the pattern being described as rod-cone in some and cone-rod in others. ERGs may be abnormal as early as age 14 months but significant cone-rod dystrophy is not apparent in most children under age five years and cooperation with ERG testing at that age is often poor. Unless strongly indicated, ERG testing may be deferred until at least age four years.

Other ophthalmologic findings can include nystagmus, strabismus, high myopia, cataract, and glaucoma.

Polydactyly. Postaxial polydactyly is common but not invariable. Presence ranges from 68% to 81% [Forsythe & Beales 2013].

Brachydactyly of the fingers and toes is common, as are partial syndactyly (most usually between the 2nd and 3rd toes), fifth-finger clinodactyly (inwardly curved little finger), and a prominent "sandal gap" between the first and second toes.

In a study of 27 affected individuals, 17 had polydactyly, four had scoliosis, two had tibia valga, two had tibia vara, and one had Legg-Calvé-Perthes disease [Ramirez et al 2004].

Obesity. Birth weight is usually normal in individuals with BBS. Significant weight gain begins within the first year and becomes a lifelong issue for most individuals. The distribution of adipose tissue is widespread in childhood but becomes most prominent in the trunk and proximal limbs in adulthood.

Obesity in BBS is thought to be multifactorial in origin. A combination of increased food intake and decreased energy expenditure is thought to underlie the development of obesity in BBS. Lower levels of physical activity have been demonstrated in persons with BBS compared to healthy controls despite comparable body mass indices [Grace et al 2003], and there is evidence of peripheral leptin resistance [Sheffield 2010].

Cognitive impairment. Although intellectual disability has been described as a major feature of BBS, often the effects of visual impairment have not been considered when assessing cognitive function. Several studies have now concluded that a majority of individuals have significant learning difficulties and only a minority have severe impairment on IQ testing [Beales et al 1999, Barnett et al 2002, Moore et al 2005]. Many indiviudals have obsessive-compulsive traits, attention difficulties, and slow thought processes [Bennouna-Greene et al 2011].

Hypogonadism/genital abnormalities. Hypogonadism, which is probably hypogonadotropic in origin, appears to be more frequent in males than females with BBS; hypogonadism may not be apparent in females until puberty when delay in onset of secondary sex characteristics and menarche become evident. Most males have micropenis at birth with small-volume testes; atrophic seminiferous tubules have been reported.

Affected females may have complex genitourinary malformations such as hypoplastic fallopian tubes, uterus and ovaries; partial and complete vaginal atresia; septate vagina; duplex uterus; hematocolpos; persistent urogenital sinus; vesico-vaginal fistula; absent vaginal orifice; and absent urethral orifice. Some of these anomalies have been described in McKusick-Kaufman syndrome; however, not all females with BBS who have these anomalies have pathogenic variants in MKKS, suggesting that this component of the syndrome is common to more than one type of BBS.

Several affected women have successfully given birth; only two affected males have been reported to have fathered children [Beales et al 1999].

Renal abnormalities. Both structural and functional renal disease has been associated with BBS [Beales et al 1999, Parfrey et al 2002]. Beales et al [1999] reported that 26 of 57 (46%) of individuals imaged had structural renal abnormalities, including calyceal clubbing or calyceal cysts, parenchymal cysts, fetal lobulation and diffuse cortical scarring, unilateral agenesis, and renal dysplasia. Clinical manifestations of structural abnormalities include decreased urine-concentrating capacity, renal tubular acidosis, and hypertension. Complications of structural malformations can include renal calculi and vesicoureteric reflux which may present with recurrent renal colic and urinary tract infection.

Progressive renal impairment frequently occurs in BBS and can lead to end-stage renal disease (ESRD), necessitating renal transplantation in up to 10% of affected individuals.

Hypertension and hyperlipidemia are common in BBS, occurring in more than 30% and 60% of affected individuals respectively [Imhoff et al 2011].

Speech impairment. Acquisition of intelligible speech and proper sentence formation is commonly delayed until age four years, but children tend to respond to early therapy. Even after language acquisition, impediments such as prolonged syllable repetition times or a tendency to substitute consonants or drop suffixes may remain [Beales et al 1999, Moore et al 2005].

Neurologic abnormalities. Ataxia and impaired coordination are encountered (≤86%), as is mild hypertonia affecting all four limbs [Beales et al 1999, Moore et al 2005]. In a study by Moore et al [2005], 75% of individuals had a paucity of facial movement sometimes associated with facial asymmetry and difficulty in smiling. As no weakness was present, they concluded that the defects were the result of impaired coordination.

Structural cerebral abnormalities described in BBS include ventriculomegaly of the lateral and third ventricles, cortical thinning, reduced size of the corpus striatum [Rooryck et al 2007], and reduced hippocampal volume and hippocampal dysgenesis [Baker et al 2011, Bennouna-Greene et al 2011].

Future clinical studies may help to further define the nature of the cognitive impairment in BBS.

Psychiatric problems. A relatively high proportion of affected individuals develop a psychiatric illness in their lifetime [Beales et al 1999, Moore et al 2005], including anxiety, mood disorders, depression, bipolar disorder, obsessive compulsive behavior, and psychosomatic manifestations. Several affected children have been reported to fall within the spectrum of autistic disorders [Barnett et al 2002, Moore et al 2005, Bennouna-Greene et al 2011].

Hearing loss. Almost half of adults with BBS develop a subclinical sensorineural hearing loss that is only detectable by audiometry [Ross et al 2005]. The implications of this finding are as yet unknown.

Glue ear (acute and chronic otitis media) resulting in conductive hearing loss early in childhood appears to be common [Beales et al 1999].

Genotype-Phenotype Correlations

Some reported genotype/phenotype correlations include the pattern of distribution of extra digits in BBS4 and characteristic ocular phenotypes in BBS2, BBS3, and BBS4 [Riise et al 2002, Héon et al 2005].

  • Individuals with pathogenic variants in BBS1 appear to have less severe ophthalmologic involvement than those with other genotypes [Daniels et al 2012].
  • Individuals with pathogenic variants in BBS10 appear to have significantly higher insulin resistance and visceral adiposity than those with BBS1 [Feuillan et al 2011].

By and large, however, correlations between phenotype and genotype have not been confirmed in large studies.


Penetrance was originally thought to be complete; however, several examples of unaffected individuals with two pathogenic variants in the same gene have been reported.


Historically, several terms have been used to describe the condition currently known as Bardet-Biedl syndrome. These include: Laurence-Moon-Biedl syndrome, Laurence-Moon-Bardet-Biedl syndrome (LMBBS), and Laurence-Moon syndrome (LMS).

JZ Laurence and RC Moon described a family with obesity, retinitis pigmentosa, and intellectual impairment in London in 1866. However, no further cases were published until the 1920s, when George Bardet reported two French girls with the triad of obesity, polydactyly, and retinitis pigmentosa; in 1922, the Austrian endocrinologist, Arthur Biedl, published a short case report of two sibs with retinitis pigmentosa, polydactyly, obesity, hypogenitalism, and intellectual impairment.

In 1925, Solis-Cohen and Weiss coined the term "Laurence-Moon-Bardet-Biedl syndrome" (LMBBS).

Ammann [1970] and Schachat & Maumenee [1982] highlighted essential differences between the Laurence-Moon and Bardet-Biedl syndromes. The medical and scientific communities have now adopted this split nomenclature. Because the family described by Laurence and Moon subsequently developed a progressive spastic paraparesis and because no mention was made of polydactyly, the Laurence-Moon syndrome is considered to comprise retinal dystrophy, obesity, hypogenitalism, and spastic paraparesis without polydactyly. In the authors' opinion and experience, little evidence exists to maintain this division and in fact, pathogenic variants have now been detected in BBS-related genes in families conforming to an LMS diagnosis [Moore et al 2005].


Among the non-consanguineous populations of northern Europe and America, the prevalence ranges from one in 100,000 (North America) to one in 160,000 (Switzerland).

Among the Bedouin peoples of Kuwait, where consanguinity is frequent, the prevalence is estimated at one in 13,500.

In the population isolate of the island of Newfoundland, Green et al [1989] reported a prevalence of one in 17,500 from a founder effect.

Differential Diagnosis

McKusick-Kaufman syndrome (MKS) is characterized by the triad of hydrometrocolpos (HMC), postaxial polydactyly (PAP), and congenital heart disease (CHD). HMC in infants is dilatation of the vagina and uterus as a result of the accumulation of cervical secretions from maternal estrogen stimulation. HMC can be caused by failure of the distal third of the vagina to develop (vaginal agenesis), a transverse vaginal membrane, or an imperforate hymen. Many cases of Bardet-Biedl syndrome (BBS) have been misdiagnosed as McKusick-Kaufman syndrome in infancy or early childhood prior to the development of other manifestations of BBS [David et al 1999]. MKS is caused by pathogenic variants in MKKS, which can also cause BBS. MKS is inherited in an autosomal recessive manner.

Alström syndrome is characterized by cone-rod dystrophy, obesity, progressive sensorineural hearing impairment, dilated cardiomyopathy, the insulin resistance syndrome, and developmental delay. Cone-rod dystrophy presents as progressive visual impairment, photophobia, and nystagmus starting between birth and age 15 months. Affected individuals have no light perception by age 20 years. Children usually have normal birth weight but become obese during their first year, resulting in childhood truncal obesity. Progressive sensorineural hearing loss presents in the first decade in as many as 70% of individuals. Hearing loss may progress to the moderately severe range (40-70 db) by the end of the first to second decade. Insulin resistance/type 2 diabetes mellitus often presents in childhood and is typically accompanied by the skin changes of acanthosis nigricans. More than 60% of individuals with Alström syndrome develop cardiac failure as a result of dilated cardiomyopathy at some stage of their lives. About 50% of individuals have delays in early developmental milestones. Males may have hypogonadotropic hypogonadism. Renal disease may present as polyuria and polydipsia resulting from a concentrating defect secondary to interstitial fibrosis. End-stage renal disease (ESRD) can occur as early as the late teens. In contrast to BBS, Alström syndrome is characterized by relative preservation of cognitive function and the absence of polydactyly. Alström syndrome is caused by pathogenic variants in ALMS1 and is inherited in an autosomal recessive manner.

Joubert syndrome is a rare condition that is genetically heterogeneous. Eighteen genes in which pathogenic variants cause Joubert syndrome have so far been identified, including NPHP1, AHI1, CEP290 (NPHP6), TMEM67 (MKS3), RPGRIP1L, CC2D2A, ARL13B, INPP5E, OFD1, TMEM216, KIF7, TCTN1, TCTN2, TMEM237, CEP41, TMEM138, CPLANE1, and TTC21B. Clinical manifestations include irregular breathing in infancy (episodic hyperpnea), developmental delay, intellectual disability, hypotonia, oculomotor apraxia, and inability to coordinate voluntary muscle movements (ataxia). Distinctive cerebellar and brain stem malformations associated with Joubert syndrome include vermis hyoplasia or agenesis (e.g., abnormalities at the pontomesencephalic junction). The characteristic molar tooth sign on cranial magnetic resonance imaging (MRI) is demonstrated by elongated but thin superior cerebellar peduncles and mild vermis hypoplasia with the resulting images reminiscent of section through a molar tooth. Dandy-Walker malformations may be evident in approximately 10% of cases as a result of abnormal cerebrospinal fluid collections in the posterior fossa. Additional clinical features include retinal dystrophy, cystic kidney disease (cystic dysplasia and nephronopthisis), ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas and endocrine abnormalities.

Senior-Løken syndrome (SLS) is another rare disorder that shares phenotypic overlap with Joubert syndrome and Bardet-Biedl syndrome. Genes identified to date include CEP290 [Sayer et al 2006], NPHP1, NPHP3 [Omran et al 2002], NPHP4 [Schuermann et al 2002], IQCB1 [Otto et al 2002], and SDCCAG8 [Otto et al 2010].

The main clinical features are retinitis pigmentosa and renal disease. Retinitis pigmentosa may present either as congenital retinal blindness caused by retinal hypoplasia or as progressive retinal degeneration later in childhood. The spectrum of cystic kidney diseases includes cystic renal dysplasia, nephronopthisis, medullary cystic kidneys, and polycystic kidneys. Presentation may occur in infancy or late childhood. Typically nephronopthisis presents in late childhood with ESRD often preceded by a long history of polydipsia and polyuria. Like Joubert syndrome and other related disorders, other features of SLS include cerebellar vermis hypoplasia and ataxia, developmental delay and intellectual disability, occiptal encephalocele, and oculomotor apraxia.

Leber congenital amaurosis (LCA), a severe dystrophy of the retina, typically becomes evident in the first year of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia, and keratoconus. Visual acuity is rarely better than 20/400. A characteristic finding is Franceschetti's oculo-digital sign, comprising eye poking, pressing, and rubbing. The appearance of the fundus is extremely variable. While the retina may initially appear normal, a pigmentary retinopathy reminiscent of retinitis pigmentosa is frequently observed later in childhood. The electroretinogram (ERG) is characteristically "nondetectable" or severely subnormal.

The diagnosis of LCA is established by clinical findings. Genes implicated in LCA include GUCY2D [Perrault et al 1996], RPE65 [Marlhens et al 1997], SPATA7 [Wang et al 2009], AIPL1 [Sohocki et al 2001], LCA5 [den Hollander et al 2007], RPGRIP1 [Dryja et al 2001, Gerber et al 2001, Hameed et al 2003, Lu & Ferreira 2005], CRX [Freund et al 1998, Swaroop et al 1999, Nakamura et al 2002], CRB1 [den Hollander et al 2001], IMPDH1 [Bowne et al 2006], RD3 [Friedman et al 2006], RDH12 [Janecke et al 2004, Perrault et al 2004, Thompson et al 2005], and CEP290. Mutation of LRAT and TULP1 may be associated with an LCA-like phenotype.

The ophthalmologic manifestations of LCA may present as a manifestation of Joubert syndrome or SLS syndrome and the fact that variants in many of the same genes are responsible for these three overlapping phenotypes leaves much to be sorted out in the nosology of these disorders.

Biemond syndrome type II (BS2) is characterized by intellectual disability, ocular coloboma, obesity, polydactyly, hypogonadism, hydrocephalus, and facial dysostosis. No responsible genes have been mapped or identified.


Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with Bardet-Biedl syndrome (BBS), the following evaluations are recommended:

  • Ophthalmologic assessment to determine visual acuity, field deficits, or refractive errors. Fundoscopic photographs should be filed for later comparison.
  • Examination of the genitalia in both sexes. It is important to image the ovaries, fallopian tubes, uterus, and vagina in all affected females. Pelvic ultrasound examination is preferred.
  • Calculation of body mass index (BMI) (weight in kg divided by the height in meters squared) can aid in identifying medically significant obesity.
  • Dietary evaluation if obesity is present (BMI >30)
  • Renal function studies and renal ultrasound examination for assessment of possible structural renal anomalies. If significant abnormalities are identified, referral to a nephrologist is desirable.
  • Baseline blood pressure assessment
  • As nephrogenic diabetes insipidus is a commonly overlooked feature of BBS, questioning the individual or parents with regard to the individual’s fluid intake and output can be a simple but helpful diagnostic aid. In some instances, tests of renal concentrating ability by initial urinalysis may be helpful.
  • Cardiac evaluation including auscultation, ECG, and echocardiography
  • Developmental assessment and/or educational evaluation for the purpose of intervention and planning
  • Endocrinologic testing as needed including glucose tolerance testing (GTT) for diabetes mellitus, lipid levels, and assessment of thyroid and liver functions. More formal tests of pituitary function may be warranted particularly in assessing fertility and development of secondary sex characteristics. Infertility should not be assumed in all males or females.
  • Hearing evaluation. Otoacoustic emissions (OAE) and audiometry may reveal subclinical sensorineural hearing loss in adults. Conductive hearing loss is common in children as a result of recurrent otitis media.
  • Dental evaluation to assess for hygiene, dental crowding, and hypodontia
  • Neurologic examination to assess for ataxic gait, poor coordination, dysdiadochokinesia, inability to perform tandem gait walking, poor two-point discrimination, and diminished fine motor skills
  • Consider referral to a clinical geneticist.

Treatment of Manifestations

No therapy exists for the progressive visual loss, but early evaluation by a low-vision specialist facilitates introduction of low vision aids and mobility training. Educational planning should take the prospect of future blindness into consideration.

To manage obesity, multiple strategies are advocated, including diet, exercise, and behavioral therapies. Education and dietary measures to control weight gain must be initiated at an early age. No formal trials of drug therapy (appetite suppressants or lipase inhibitors) have been reported; however, such therapy may be attempted providing the individual does not have contraindications to specific drug use (i.e., renal or hepatic dysfunction).

Complications of obesity, such as hypercholesterolemia and diabetes mellitus, should be treated as in the general population.

Cognitive disability should be addressed through early intervention and special education, as indicated by evaluation. It is advisable to assess individual needs with respect to education, as many adults are capable of attaining independent living skills.

Speech therapy should be offered at the first sign of speech delay and/or impairment.

Renal transplantation has been successful, although the immunosuppressants used following transplantation can compound the weight problem.

Surgical correction of hydrocolpos, vaginal atresia, or hypospadias may be warranted.

As children approach puberty, gonadotropin and sex hormone levels should be monitored to determine if hormone replacement therapy is indicated.

It is important to offer contraceptive advice to all affected females rather than assume likely infertility.

The earliest and most common intervention for polydactyly is removal of the accessory digit. Indicators are functional interference and poorly fitting footwear. Most children have their accessory digits removed within the first two years.

Treatment of cardiac abnormalities is the same as for the general population.

Dental extractions are appropriate as required for dental crowding.

Prompt treatment for acute and chronic otitis media should be considered. Insertion of grommets is commonplace.

Prevention of Secondary Complications

Antibiotic prophylaxis for surgical and dental procedures is indicated for individuals with structural cardiac anomalies.


A multidisciplinary approach is required to effectively manage this pleiotropic condition. Suggested surveillance is summarized here:

  • Annual ophthalmologic evaluations with annual electroretinogram in those older than age five years
  • Routine (at least annual) measurement of blood pressure
  • A baseline renal ultrasound scan and annual renal function tests for all individuals with BBS. If a structural renal malformation is detected, review by a nephrologist and follow-up sonography is indicated.
    • Monitor BUN and serum concentration of creatinine if a progressive obstructive urinary tract anomaly is detected or if bilateral renal malformations are observed and satisfactory renal growth is not observed on follow-up ultrasonography.
    • In individuals with renal impairment (elevated serum creatinine) as a result of an underlying structural malformation, six-month to annual monitoring by a nephrologist for complications of chronic kidney disease is indicated.
  • Annual endocrinology review
    • Regular testing for diabetes mellitus by measurement of fasting glucose concentration or glucose tolerance testing
    • Annual thyroid function tests, liver function tests and lipid profile

Agents/Circumstances to Avoid

Any substances contraindicated in persons with renal impairment should be avoided.

Evaluation of Relatives at Risk

Sibs or relatives who have clinical features similar to those of the individual with BBS warrant genetic consultation. If the relative is deemed affected, molecular genetic testing, consultation with an ophthalmologist, and a renal sonogram to evaluate for structural renal malformations are recommended.

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Pregnancy Management

Expectant mothers affected with BBS require close monitoring for any deterioration in renal function or pregnancy-related complications due to structural abnormalities of the reproductive tract.

Therapies Under Investigation

Search in the US and in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

Bardet-Biedl syndrome (BBS) is usually inherited in an autosomal recessive manner (see Related Genetic Counseling Issues, Multiallelic inheritance).

Risk to Family Members

Parents of a proband

  • The parents of an affected child are obligate heterozygotes (i.e., carriers of one mutated allele).
  • Heterozygotes (carriers) are asymptomatic.

Sibs of a proband

  • At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
  • Once an at-risk sib is known to be unaffected, the chance of his/her being a carrier is 2/3.
  • Heterozygotes (carriers) are asymptomatic.

Offspring of a proband. The offspring of an individual with BBS are obligate carriers for a pathogenic variant.

Other family members of a proband. Each sib of the proband's parents is at a 50% risk of being a carrier.

Carrier (Heterozygote) Detection

Carrier testing using molecular genetic techniques is possible for at-risk family members when the pathogenic variants in the family are known.

Related Genetic Counseling Issues

See Management, Evaluation of Relatives at Risk for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.

Family planning

  • The optimal time for determination of genetic risk, clarification of carrier status, and discussion of the availability of prenatal testing is before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.

Multiallelic inheritance. The risks outlined above are those for straightforward autosomal recessive patterns of disease inheritance. However, some cases of BBS appear to require the presence of at least three pathogenic variants for the phenotype to manifest (triallelic inheritance).

Katsanis et al [2001] proposed that BBS may also be inherited in a more complex fashion, as an oligogenic disorder. They described a number of pedigrees in which individuals were homozygous or compound heterozygous for variants at one locus, but required the presence of a third heterozygous variant residing at a second BBS locus to manifest the disease phenotype — a pattern termed triallelism.

Following the identification of BBS1, Mykytyn et al [2002] and Mykytyn et al [2003] failed to find any examples of multiallelic inheritance in their cohort to support the theory of Katsanis et al [2001]. Beales et al [2003] found evidence for more than two variants at two BBS gene loci including BBS1. Badano et al [2003] reported a family with multiallelism involving BBS7.

Fauser et al [2003] reported examples of complex inheritance in 21 persons with BBS. In testing six BBS-related genes in 27 families, Hichri et al [2005] did not identify any individuals with pathogenic variants in more than one BBS-related gene; however, the excess of heterozygous variants observed was consistent with complex inheritance.

More recently, mutation of MKS1 and CEP290 has been shown to cause BBS and to have a possible epistatic effect on variants at other known BBS loci [Leitch et al 2008].

Abu-Safieh et al [2012] sequenced BBS1-14 in 29 BBS families and found no evidence for triallelism.

At present, the extent to which possible multiallelism accounts for the phenotype is unknown. In practical terms, however, identification of such families is difficult and by previous estimations may account for fewer than 10% of all families with BBS. Therefore, until testing improves and further multiallelic affected individuals are reported, it is prudent to use autosomal recessive risk figures when providing genetic counseling and to note that in some affected individuals, BBS may not conform to Mendelian laws of inheritance.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing and Preimplantation Genetic Diagnosis

Molecular genetic testing. Once the pathogenic variants have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis for BBS are possible.

Ultrasound examination in pregnancies at increased risk. Prenatal diagnosis using second-trimester ultrasound examination to detect anomalies such as postaxial polydactyly and renal cysts found in BBS has been reported [Dar et al 2001]. Cassart et al [2004] studied 11 pregnancies by ultrasound examination and concluded that in families in which BBS had occurred previously, the prenatal appearance of enlarged hyperechoic kidneys without corticomedullary differentiation should be considered recurrence of BBS.

Ultrasound examination in pregnancies not known to be at increased risk. When antenatal ultrasonography reveals large hyperechoic kidneys with loss of corticomedullary differentiation in the presence of polydactyly a diagnosis of BBS or Meckel syndrome should be considered [Dippell & Varlam 1998, Cassart et al 2004].


GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

  • Laurence-Moon-Bardet-Biedl Society (LMBBS)
    10 High Cross Road
    Rogerstone Newport NP10 9AD
    United Kingdom
    Phone: +44 1633 718415
  • Foundation Fighting Blindness
    11435 Cronhill Drive
    Owings Mills MD 21117-2220
    Phone: 800-683-5555 (toll-free); 800-683-5551 (toll-free TDD); 410-568-0150
  • Retina International
    Retina Suisse
    Ausstellungsstrasse 36
    Zurich CH-8005
    Phone: +41 (0) 44 444 1077
    Fax: +41 (0) 44 444 1070
  • EURO-WABB Project Registry
    An EU Rare Diseases Registry for Wolfram syndrome, Alstrom syndrome, Bardet-Biedl syndrome and other rare diabetes syndromes.

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A.

Bardet-Biedl Syndrome: Genes and Databases

Locus NameGeneChromosome LocusProteinLocus-Specific DatabasesHGMDClinVar
BBS1BBS111q13​.2Bardet-Biedl syndrome 1 proteinRetina International Mutations of the Bardet-Biedl Syndrome Type 1 Gene (BBS2L2)
BBS1 database
BBS2BBS216q13Bardet-Biedl syndrome 2 proteinRetina International Mutations of the Bardet-Biedl Syndrome Type 2 Gene (BBS2)BBS2BBS2
BBS3ARL63q11​.2ADP-ribosylation factor-like protein 6ARL6 @ LOVDARL6ARL6
BBS4BBS415q24​.1Bardet-Biedl syndrome 4 proteinRetina International Mutations of the Bardet-Biedl Syndrome Type 4 Gene (BBS4)BBS4BBS4
BBS5BBS52q31​.1Bardet-Biedl syndrome 5 proteinBBS5 @ LOVDBBS5BBS5
BBS6MKKS20p12​.2McKusick-Kaufman/Bardet-Biedl syndromes putative chaperoninRetina International Mutations of the McKusick-Kaufman Gene (MKKS)MKKSMKKS
BBS7BBS74q27Bardet-Biedl syndrome 7 proteinRetina International Mutations of the Bardet-Biedl Syndrome Type 7 Gene (BBS2L1)BBS7BBS7
BBS8TTC814q31​.3Tetratricopeptide repeat protein 8TTC8 databaseTTC8TTC8
BBS10BBS1012q21​.2Bardet-Biedl syndrome 10 proteinBBS10 @ LOVDBBS10BBS10
BBS11TRIM329q33​.1E3 ubiquitin-protein ligase TRIM32TRIM32 homepage - Leiden Muscular Dystrophy pagesTRIM32TRIM32
BBS12BBS124q27Bardet-Biedl syndrome 12 proteinBBS12 @ LOVDBBS12BBS12
BBS13MKS117q22Meckel syndrome type 1 proteinMKS1 @ LOVDMKS1MKS1
BBS14CEP29012q21​.32Centrosomal protein of 290 kDaCEP290CEP290
BBS15WDPCP2p15WD repeat-containing and planar cell polarity effector protein fritz homologWDPCP @ LOVDWDPCPWDPCP
BBS16SDCCAG81q43-q44Serologically defined colon cancer antigen 8SDCCAG8 @ LOVDSDCCAG8SDCCAG8
BBS17LZTFL13p21​.31Leucine zipper transcription factor-like protein 1LZTFL1 @ LOVDLZTFL1LZTFL1
BBS18BBIP110q25​.2BBSome-interacting protein 1BBIP1BBIP1
BBS19IFT2722q12​.3Intraflagellar transport protein 27 homologIFT27IFT27

Data are compiled from the following standard references: gene from HGNC; chromosome locus from OMIM; protein from UniProt. For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click here.

Table B.

OMIM Entries for Bardet-Biedl Syndrome (View All in OMIM)

209901BBS1 GENE; BBS1
600374BBS4 GENE; BBS4
603650BBS5 GENE; BBS5
606151BBS2 GENE; BBS2
607590BBS7 GENE; BBS7
609883MKS1 GENE; MKS1
610148BBS10 GENE; BBS10
610683BBS12 GENE; BBS12

Molecular Genetic Pathogenesis

Ciliary defects. Defects in cilia or intraflagellar transport (IFT) have been associated with several human disorders including Bardet-Biedl syndrome (BBS), Kartagener syndrome (see Primary Ciliary Dyskinesia), autosomal dominant polycystic kidney disease, and nephronophthisis.

Cilia protrude from almost all vertebrate cells and extend from basal bodies within the cell. Cilia are classified as primary cilia or motile cilia. Primary cilia have a 9+0 axonemal microtubule formation, are usually immotile, lack dynein arms, and are hypothesized to function as sensory organelles [Pazour & Witman 2003]. Motile cilia have a 9+2 axonemal microtubule formation and are usually involved in generating flow or movement. The assembly and maintenance of cilia depend on intraflagellar transport that moves particles from the basal body along the microtubular structure of the ciliary axoneme to the tip.

A significant leap in understanding the molecular pathogenesis of BBS emerged from the discovery of BBS8, which led to the proposal of ciliary involvement in BBS [Ansley et al 2003]. Compelling evidence was subsequently provided from comparative genomic studies that identified all known BBS orthologs among genes present exclusively in ciliated organisms [Avidor-Reiss et al 2004, Li et al 2004]. All known C. elegans bbs orthologs are exclusively expressed in a subset of ciliated sensory neurons [Ansley et al 2003, Fan et al 2004, Li et al 2004], and bbs-7 and bbs-8 mutants have structural and functional ciliary defects [Blacque et al 2004]. Furthermore, several BBS proteins localize to the centrosome (the "microtubule organizing center" of the cell) and basal body (a product of the centrosome that is positioned at the base of the cilium and required for cilia formation) [Ansley et al 2003, Kim et al 2004, Li et al 2004, Kim et al 2005]. A study of the BBS4 protein suggested that it may act as an adaptor protein facilitating the microtubule-dependent intracellular transport within the cilium or in the cytosol [Kim et al 2004]. A summary of the localization and putative role of the BBS proteins is illustrated in Figure 2.

Figure 2. . Schematic diagram of the primary cilium illustrating the concept of intraflagellar transport (IFT) and the component parts therein.

Figure 2.

Schematic diagram of the primary cilium illustrating the concept of intraflagellar transport (IFT) and the component parts therein. The protein cargo is manufactured in the Golgi apparatus and carried by vesicles to the cell membrane where receptor proteins (more...)

Pathogenesis of anosmia. Studies of mouse knockouts of Bbs1 [Kulaga et al 2004], Bbs2 [Nishimura et al 2004], Bbs4 [Kulaga et al 2004, Mykytyn et al 2004] and Bbs6 [Fath et al 2005, Ross et al 2005] have provided further support for ciliary involvement in BBS. Mice display sperm flagellation defects, retinal degeneration likely secondary to defective IFT, as well as olfactory dysfunction presenting as partial or complete anosmia with diminution of the ciliated olfactory epithelium. Humans with BBS were subsequently identified with partial or complete anosmia [Kulaga et al 2004, Iannaccone et al 2005].

Pathogenesis of rod-cone dystrophy. Defects in the transport of phototransduction proteins from the inner to the outer segments of photoreceptors leads to cell death and is thought to underlie the pathogenesis of retinitis pigmentosa in BBS [Nishimura et al 2004, Mockel et al 2011]. In addition, defects in synaptic transmission from the photoreceptors to secondary neurons of the visual system have also been reported to occur in Bbs4-null mice, thereby suggesting multiple functions for BBS4 in photoreceptors.

Pathogenesis of polydactyly. Aberrant sonic hedgehog signaling has been suggested to account for the features of polydactyly in BBS. Recently, zebrafish bbs morphants have been shown to have altered sonic hedgehog expression associated with abnormal fin bud patterning reminiscent of polydactyly in BBS [Tayeh et al 2008].

Pathogenesis of obesity. Recent findings have demonstrated that the development of obesity in murine models of BBS is associated with increased food intake and decreased locomotor activity [Rahmouni et al 2008].

Defects in leptin action may be responsible for the development of obesity in BBS. Leptin under normal physiologic circumstances suppresses appetite and increases energy expenditure by activating leptin receptors on specific neurons. In murine BBS, high circulating levels of leptin have been demonstrated and exogenous leptin administration fails to decrease body weight and food intake thereby suggesting that leptin resistance likely underlies the development of obesity in BBS [Rahmouni et al 2008]. Interestingly, loss of cilia specifically in proopiomelanocortin (POMC) neurons can result in an increase in weight and adiposity, suggesting that cilia on hypothalamic neurons may play a key role mediating feeding behavior through the perception of satiety cues such as leptin. Leptin has been shown to excite POMC neurons in the presence of high glucose levels to signal to reduce food intake. High leptin levels and POMC gene expression is reduced in Bbs-null mice thereby suggesting a role for BBS proteins in mediating leptin signaling within the hypothalamus. Other recent studies suggest that BBS proteins may also be involved in adipogenesis and future studies will need to determine whether hypothalamic dysfunction alone is sufficient to account for the obesity phenotype observed in BBS [Forti et al 2007].

For a detailed summary of gene and protein information for the genes listed below, see Table A, Gene.


Gene structure. BBS1 is composed of 17 exons (NM_024649.4) and encodes a 593-amino acid protein, with the ATG start codon lying within exon 1 [Mykytyn et al 2002, Beales et al 2003, Mykytyn et al 2003].

Pathogenic variants. A common p.Met390Arg pathogenic variant within exon 12 of BBS1 was shown to be involved in 30% of individuals in a cohort of 129 probands with BBS [Mykytyn et al 2003]. In a further study of 259 individuals with BBS, a total of 74 p.Met390Arg mutated alleles were identified, with p.Met390Arg contributing to 18% of the cohort and involved in 79% of all families with BBS1 pathogenic variants [Beales et al 2003]. In addition, frameshift and nonsense variants have been identified within the BBS1 coding sequence. See Table 2 (pdf). For more information, see Table A.

Normal gene product. The sequence of the protein encoded by BBS1 displays no significant homology to any other known proteins, with the exception of a region near the N terminal shared with BBS2 and BBS7 containing a predicted beta-propeller domain. In C. elegans it is expressed exclusively in ciliated cells and predominantly localizes to the transition zones (akin to basal bodies) as well as moving bidirectionally along the ciliary axoneme [Blacque et al 2004].

Abnormal gene product. Bbs1-null mice display olfactory deficiencies and defects in olfactory structure and function [Kulaga et al 2004].


Gene structure. BBS2 is composed of 17 exons (NM_031885.3) and encodes a 721-amino acid protein; the start codon lies within exon 1 [Nishimura et al 2001].

Benign variants. See Table 3 (pdf).

Pathogenic variants. A variety of nucleotide changes resulting in frameshift, nonsense, and missense variants have been identified throughout BBS2; there is no known mutational hot spot. See Table 4 (pdf) [Katsanis et al 2000, Katsanis et al 2001, Nishimura et al 2001, Katsanis et al 2002]. For more information, see Table A.

Normal gene product. The sequence of the protein encoded by BBS2 displays no significant homology to any other known proteins, with the exception of a region near the N terminal shared with BBS1 and BBS7 containing a predicted beta-propeller domain. In C. elegans it is expressed exclusively in ciliated cells and predominantly localizes to the transition zones (akin to basal bodies) as well as moving bidirectionally along the ciliary axoneme [Blacque et al 2004].

Abnormal gene product. Bbs2-null mice display obesity, retinal degeneration, renal cysts, male infertility, and olfactory deficiencies [Nishimura et al 2004].


Gene structure. ARL6 is composed of nine exons (NM_032146.3) and encodes a 186-amino acid protein; the start codon lies within exon 3 [Chiang et al 2004, Fan et al 2004].

Pathogenic variants. Mutation of ARL6 accounts for a very small percentage of BBS (~0.4%). To date, only four homozygous missense variants and one nonsense variant have been identified within the coding sequence. For more information, see Table A.

Normal gene product. ARL6 encodes an ADP-ribosylation-like factor (ARL) protein that belongs to the Ras superfamily of small GTP-binding proteins essential for various membrane-associated intracellular trafficking events [Chiang et al 2004, Fan et al 2004]. The C. elegans ARL6 ortholog is specifically expressed in ciliated cells and undergoes IFT within the ciliary axoneme [Fan et al 2004].

Abnormal gene product. Protein modeling suggests that the four missense variants identified so far (p.Gly169Ala, p.Thr31Met, p.Leu170Trp, and p.Thr31Arg) alter residues near or within the GTP-binding site and are therefore likely to abrogate GTP binding [Fan et al 2004].


Gene structure. BBS4 is composed of 16 exons (NM_033028.4) and has an open reading frame of 519 codons with the start codon positioned within the first exon [Mykytyn et al 2001].

Benign variants. See Table 5 (pdf).

Pathogenic variants. A variety of nucleotide changes resulting in frameshift, nonsense, and missense variants have been identified throughout BBS4, as well as two deletions of multiple exons. There is no known mutational hot spot. See Table 6 (pdf) [Katsanis et al 2001, Mykytyn et al 2001, Katsanis et al 2002, Nishimura et al 2005]. For more information, see Table A.

Normal gene product. The protein encoded by BBS4 contains at least ten TPR domains, which are thought to be involved in protein-protein interactions. It localizes to the basal body and centrosome in cultured cells and may function as an adaptor protein facilitating the loading of cargo onto the dynein-dynactin molecular motor in preparation for microtubule-dependent intracellular transport within the cilium or in the cytosol [Kim et al 2004].

Abnormal gene product. Mice null for Bbs4 are obese and have retinal degeneration, sperm flagellation defects, olfactory deficiencies, and defects in olfactory structure and function [Kulaga et al 2004, Mykytyn & Sheffield 2004]. Silencing of BBS4 in cultured cells leads to de-anchoring of microtubules, arrest of cell division, and apoptotic cell death [Kim et al 2004].


Gene structure. BBS5 is composed of 12 exons (NM_152384.2) and has an open reading frame of 342 codons [Li et al 2004].

Pathogenic variants. Mutation of BBS5 accounts for a very small percentage of BBS (~0.4%). To date, one splice donor variant that leads to a frameshift and a premature termination codon in exon 7, two nonsense variants [Li et al 2004], and one multiexon deletion [Nishimura et al 2005] have been identified. For more information, see Table A.

Normal gene product. The protein encoded by BBS5 localizes to the basal bodies and faintly within the ciliary axoneme in the ependymal cells lining the ventricles of the brain in mouse [Li et al 2004]. In C. elegans, bbs-5 is expressed exclusively in ciliated cells and predominantly localizes to the base of the cilia in ciliated head and tail neurons [Li et al 2004].

Abnormal gene product. Silencing of BBS5 in Chlamydomonas results in an aflagellated phenotype [Li et al 2004].


Gene structure. MKKS comprises six exons (NM_018848.3) and encodes a 570-amino acid protein [Stone et al 2000]. The start codon lies within exon 3. Two alternatively spliced 5' exons are not translated. For a detailed summary of gene and protein information, see Table A, Gene.

Benign variants. See Table 7 (pdf) [Stone et al 2000, Slavotinek et al 2002].

Pathogenic variants. Nucleotide changes have been identified in all of the coding exons of MKKS that result in frameshift, nonsense, and missense variants; there is no known mutational hot spot. For a number of individuals, only one heterozygous variant has been identified; one possible explanation includes triallelic inheritance, as these individuals may harbor pathogenic variants at one of the other BBS loci [Katsanis et al 2001]. See Table 8 (pdf). For more information, see Table A.

Normal gene product. The 570-amino acid protein encoded by MKKS [Stone et al 2000] shows strong homology to archaebacterial chaperonins and the eukaryotic T-complex-related proteins (TCPs), which belong to the type II class of chaperonins [Kim et al 2005]. These proteins are implicated in facilitation of nascent protein folding in an ATP-dependent manner (reviewed by Wickner et al [1999]). MKKS localizes to the pericentriolar material (PCM), a proteinaceous tube surrounding centrioles but during mitosis it is also found at intracellular bridges [Kim et al 2005].

Abnormal gene product. The predicted substrate binding apical domain of the protein encoded by MKKS is sufficient for centrosomal localization, but several patient-derived missense variants in this domain (p.Gly52Asp, p.Asp285Ala, p.Thr325Pro, and p.Gly345Glu) result in the protein mislocalization in cells [Kim et al 2005]. Silencing of MKKS in cultured cells leads to multinucleate and multicentrosomal cells with cytokinesis defects [Kim et al 2005]. Mice null for Mkks/Bbs6 are obese and have retinal degeneration, sperm flagellation defects, olfactory deficiencies, and defects in olfactory structure and function [Fath et al 2005, Ross et al 2005].


Gene structure. BBS7 is composed of 19 exons (NM_018190.3) and encodes a 672-amino acid protein (NP_060660.2) [Badano et al 2003]. An alternative isoform produced by differential splicing of an alternative exon 18 results in an additional 44 residues and a discrete 3' UTR [Badano et al 2003].

Pathogenic variants. Only four different pathogenic variants have been identified in BBS7 thus far: one that results in a frameshift and the introduction of a premature termination codon, two missense variants, and one multiexon deletion [Badano et al 2003, Nishimura et al 2005]. See Table 9 (pdf). For more information, see Table A.

Normal gene product. The sequence of the protein encoded by BBS7 displays no significant homology to any other known proteins, with the exception of a region near the N terminal shared with BBS1 and BBS2 containing a predicted beta-propeller domain. In C. elegans, it is expressed exclusively in ciliated cells and predominantly localizes to the transition zones (akin to basal bodies) as well as moving bidirectionally along the ciliary axoneme [Blacque et al 2004].

Abnormal gene product. C. elegans with mutation of the bbs-7 ortholog have structural and functional ciliary defects and compromised intraflagellar transport [Blacque et al 2004].


Gene structure. TTC8 is composed of 15 exons (NM_144596.2) and encodes a 531-amino acid protein.

Pathogenic variants. Mutation of TTC8 accounts for only a small percentage of BBS. Two families with identical six base-pair deletions resulting in the deletion of two amino acids and another with a three base-pair deletion abolishing the splice donor site of exon 10 have been identified [Ansley et al 2003]. For more information, see Table A.

Normal gene product. BBS8 was identified because of its similarity to the BBS4 protein, containing eight TPR domains possibly involved in protein-protein interactions [Ansley et al 2003]. It also exhibits similarity to a prokaryotic domain pilF involved in twitching mobility and type-IV pilus assembly. The BBS8 protein localizes to the centrosome and basal body of cultured ciliated cells [Ansley et al 2003]. In C. elegans it is expressed exclusively in ciliated cells and predominantly localizes to the transition zones (akin to basal bodies) as well as moving bidirectionally along the ciliary axoneme [Ansley et al 2003, Blacque et al 2004].

Abnormal gene product. C. elegans with mutation of the bbs-8 ortholog have structural and functional ciliary defects and compromised intraflagellar transport [Blacque et al 2004].

BBS9 (B1)

Gene structure. The parathyroid hormone-responsive gene B1 (B1) was recently identified as BBS9 [Nishimura et al 2005]. It is composed of 25 exons, with all except the first contributing to its various protein isoforms that range between 879 and 916 amino acids in length.

Pathogenic variants. A total of seven BBS9 variants, including nonsense, splice site, missense, frameshift, and one single- and one multiexon deletion have been identified [Nishimura et al 2005]. For more information, see Table A.

Normal gene product. PTHB1 is widely expressed. It has no similarity to other BBS proteins and its specific function is unknown.

Abnormal gene product. PTHB1 is downregulated in the retina of Bbs4-null mice [Nishimura et al 2005].


Gene structure. A vertebrate-specific chaperonin-like gene was recently identified as BBS10 (NM_024685.3) [Stoetzel et al 2006]. It is composed of two exons encoding a 723-amino acid protein, with the start codon contained within exon 1.

Pathogenic variants. BBS10 is a major locus for BBS, contributing mutated alleles in approximately 20% of all individuals with BBS. There are numerous missense, frameshift, and nonsense variants spread throughout the coding region, with no mutational hot spot [Stoetzel et al 2006].

Normal gene product. BBS10 has a chaperonin domain organization conserved with all three major functional domains — equatorial, intermediate, and apical — and the flexible protrusion region specific to group II chaperonins. The ATP hydrolytic domain is conserved in BBS10, suggesting that it may be an active enzyme, in contrast to BBS6, where this catalytic site is absent.

Abnormal gene product. Suppression of bbs10 expression in zebrafish embryos causes shortening of the body axis and dorsal thinning, broadening and kinking of the notochord, and elongation of the somites [Stoetzel et al 2006].

TRIM32 (BBS11)

Gene structure. TRIM32, a ubiquitin ligase, was recently identified [Chiang et al 2006]. It is composed of two exons (NM_012210.3) encoding a 652-amino acid protein, with the ATG start codon in exon 2.

Pathogenic variants. The only TRIM32 pathogenic variant identified to date to be associated with BBS is a homozygous missense variant p.Pro130Ser, which lies in the N-terminal B-box domain, in affected individuals in an inbred Bedouin Arab family [Chiang et al 2006]. However, a missense variant, p.Asp487Asn in the C-terminal NHL domain of TRIM32, was previously associated with autosomal recessive limb-girdle muscular dystrophy (LGMD) [Frosk et al 2002].

Normal gene product. TRIM32 is a member of the TRIM family that is characterized by a common domain structure composed of a RING finger, B-box, and a coiled-coiled motif. It also contains five C-terminal NHL repeats. TRIM32 is thought to have E3 ubiquitin ligase activity, binds to myosin, and ubiquitinates actin, implicating TRIM32 in regulating components of the cytoskeleton.

Abnormal gene product. Zebrafish embryos with knockdown of TRIM32 expression display an abnormal Kuppfer’s vesicle, a transient ciliated organ involved in left-right patterning, and a delay in melanosome transport. The p.Pro130Ser mutated allele associated with BBS fails to rescue these abnormal phenotypes, in contrast to the p.Asp487Asn allele associated with LGMD, suggesting that each variant disrupts different functions of TRIM32 [Chiang et al 2006].


Gene structure. BBS12 encodes a vertebrate-specific predicted chaperonin-like protein [Stoetzel et al 2007]. The gene is composed of two exons (NM_152618.2), of which only the second is coding, for a predicted protein of 710 amino acids.

Pathogenic variants. BBS12 is mutated in approximately 5% of families affected with BBS [Stoetzel et al 2007]. Variants identified include frameshift (one of which, p.Phe372Ter [also known as F372fsX373], is recurrent and present in several families), nonsense variants, small in-frame deletions, a variant that is predicted to extend the C-terminus of the protein, and missense alleles.

Normal gene product. BBS12 is related to the group II chaperonins and to a family of vertebrate-specific chaperonin-like sequences encompassing BBS10 and BBS6 [Stoetzel et al 2007]. The classic chaperonin domain architecture (equatorial, intermediate, and apical domains) is conserved, but BBS12 has an additional five specific inserted sequences within the intermediate and equatorial domains. However, the functional ATP hydrolysis motif is not conserved in BBS12, as is the case for BBS6.

Abnormal gene product. Injection of bbs12-specific morpholino (antisense oligonucleotides) into zebrafish embryos results in phenotypes consistent with convergence and extension (CE) defects, including shortened body axis, broadened somites, kinked notochord and dorsal thinning [Stoetzel et al 2007]. Simultaneous suppression of bbs12, bbs10, and bbs6 gene expression yielded similar but more severe phenotypes, suggesting a possible partial functional redundancy within this protein family.

MKS1 (BBS13)

Gene structure. MKS1 contains 17 exons (NM_017777.3) and encodes a 559-amino acid polypeptide containing a conserved B9 domain of unknown function [Leitch et al 2008]. Four splice variants are known.

Pathogenic variants. MKS1 accounts for approximately 4.5% of the total mutational load in BBS. Variants identified include heterozygous missense variants such as p.Arg123Gln, identified in two unrelated families, one of Lebanese origin; in the affected individual, a homozygous frameshift variant in BBS10, p.Ser73fsTer91, was also identified. Similarly, the p.Arg123Gln variant was also described in a Saudi family with a pathogenic heterozygous variant in BBS10 (p.Gln242fsTer258). Another heterozygous variant, p.Val339Met, was detected in a third Middle Eastern family who also had a homozygous BBS1 variant, p.Arg146Ter. In a fifth family of northern European descent, another variant, p.Ile450Thr, was also found. A sixth pedigree of Turkish descent was found to be compound heterozygous for two pathogenic MKS1 variants that segregated in an autosomal recessive fashion: an allele resulting in p.Cys492Trp substitution and a base pair deletion that removes phenylalanine (p.Phe371del) [Leitch et al 2008].

Normal gene product. Mks proteins have been localized to either the basal body, primary cilium, or both [Dawe et al 2007, Delous et al 2007, Williams et al 2008]. Mks1 is one of six Mks proteins that is identified by the conserved B9 domain, the function of which is unclear. Nematode mks proteins also contain B9 domains and like their mammalian orthologs localize to the transition zones/basal bodies of sensory cilia, thereby demonstrating a conserved role for Mks proteins in ciliary function. Supporting this hypothesis is the finding of X-box consensus sequences lying within the promoter regions of these proteins. X-box sequences are recognized and regulated by the daf-19 or rfx family of transcription factors and thereby regulate the transcription of ciliogenic programs [Blacque et al 2005, Efimenko et al 2005].

Abnormal gene product. Human variants in MKS1 lead to a ciliopathy phenotype characterized by encephalocele, cystic kidneys, hepatic fibrosis, and polydactyly. Knockdown of the human MKSR1 and MKSR2 (MKS-related protein 1 and 2) using RNA interference leads to a ciliogenesis defect [Bialas et al 2009]. Co-injection of MKS1 mRNA encoding the pathogenic MKS variants p.Asp123Gln, p.Asp286Gly, and p.Cys492Trp with mks1 morpholino in zebrafish does not rescue the gastrulation defect to the same degree as wild-type MKS1 mRNA [Leitch et al 2008].

CEP290 (NPHP6) (BBS14)

Gene structure. CEP290 is also known as 3H11Ag, BBS14, FLJ13615, JBTS5, KIAA0373, LCA10, MKS4, NPHP6, and SLSN6. It contains 54 exons (NM_025114.3) which encode for a polypeptide of 2481 amino acids. Two splice variants are known.

Pathogenic variants. Mutation of CEP290 has been associated with a number of ciliopathies including BBS [Sayer et al 2006, Baala et al 2007, Helou et al 2007, Leitch et al 2008]. A homozygous nonsense variant in CEP290, p.Glu1903Ter, was identified in an individual with BBS born to a consanguineous Saudi couple [Leitch et al 2008]. This individual also carried a complex compound heterozygous variant in TMEM67 (MKS3) (p.Gly218Ala and p.Ser320Cys) [Leitch et al 2008]. The clinical manifestations in this person included retinitis pigmentosa, nystagmus, renal disease, developmental delay, obesity, and intellectual disability. Zebrafish embryos injected with both cep290 and mks morpholino show severe gastrulation defects, shortened body axis, widened notochords, and broad somites [Leitch et al 2008].

Normal gene product. CEP290 localizes to the centrosome and basal bodies of cilia in renal epithelial cells and the connecting cilium of photoreceptor cells. CEP290 has recently been shown to interact with another ciliary protein, PCM-1, a centriolar satellite protein [Kim et al 2008]. CEP290 and PCM-1 bind to each other and localize to centriolar satellites in a microtubule-dependent manner and CEP290 appears to be required for the integrity of the cytoplasmic microtubular network. Furthermore, both CEP290 and PCM-1 are required for ciliogenesis and play a role in targeting the small GTPase Rab8 to the ciliary membrane [Kim et al 2008].

Abnormal gene product. The CEP290 p.Glu1903Ter variant results in a truncated C-terminus of 576 amino acids. This allele was not found in 96 ethnically matched controls, in 184 European descended controls, or in any publicly available SNP database, thereby supporting a pathogenic variant as accountable for the BBS phenotype [Leitch et al 2008].


Gene structure. WDPCP contains 12 exons and a transcript of 3326 bp (NM_015910.5).

Pathogenic variants. Mutation of WDPCP may be associated with BBS based on the following: Kim et al [2010] identified a homozygous G>T transition at the -1 position of a splice site in WDPCP in a child with BBS. The parents and an unaffected sib were carriers of this variant; the variant was not found in 384 control chromosomes or in individuals in the HapMap project or the 1,000 genomes project [Kim et al 2010]. However, neither transcript analysis nor other evidence of pathogenicity was presented.

Normal gene product. WDPCP encodes WD repeat-containing and planar cell polarity effector protein fritz homolog.

Abnormal gene product. A splice defect has been identified, but it is not known how this affects the transcript or if an abnormal gene product is produced.


Gene structure. This gene has 18 exons and a transcript of 2632 bp (NM_006642.3). For a detailed summary of gene and protein information, see Table A, Gene.

Pathogenic variants. Mutation of WDPCP may be associated with BBS based on the following: Individuals in one large family with BBS, were homozygous for a complex intron 7 insertion that disrupted an exonic splice enhancer site and created a premature stop codon. Detailed analysis of transcripts and proteins demonstrated a near complete absence of normal full-length protein product of SDCCAG8 [Otto et al 2010]. Sibs of east Indian origin with a diagnosis of BBS, severe renal involvement, and absence of polydactyly were found to have compound heterozygous variants in SCCAG8 (p.Thr482LysfsTer12 and p.Asp543AlafsTer24) [Billingsley et al 2012].

Normal gene product. SDCCAG8 encodes a centrosome associated protein that may be involved in organizing the centrosome during interphase and mitosis.

Abnormal gene product. This variant led to a near-complete absence of normal full-length protein product from SDCCAG8. The residual full-length transcript and product was proposed as an explanation for the late onset of renal failure and retinal degeneration in affected persons of this kindred [Otto et al 2010].


Gene structure. LZTFL1 encodes leucine zipper transcription factor-like protein 1. The gene has ten exons and a transcript of 4073 bp (NM_020347.2).

Pathogenic variants. Mutation of LZTFL1 may be associated with BBS based on the following: Schaefer et al [2014] report dizygotic twins with a clinical diagnosis of BBS where sequencing of LZTFL1 revealed a compound heterozygous mutation of a missense c.260T>C (p.Leu87Pro) and a nonsense c.778G>T (p.Glu260Ter) alteration. The twins presented with retinitis pigmentosa, learning difficulties, renal dysfunction, and (most notably) insertional polydactyly bilaterally. Marion et al [2012] also reported a patient presenting with BBS including situs intersus and insertional polydactyly with a homozygous 5-bp deletion in LZTFL1.

Normal gene product. The LZTFL1 product, leucine zipper transcription factor-like protein 1 (LZTFL1), is ubiquitously expressed and localizes to the cytoplasm. It is an important negative regulator of the BBSome ciliary trafficking and sonic hedgehog pathway signaling [Seo et al 2011].

Abnormal gene length product: LZTFL1 protein expression was halved in affected individuals and the variant was not found in 176 healthy controls analyzed by exome sequencing. The LZTFL1 protein was detected at 30 kd by western blot in dermal fibroblasts and not at 35 kd as expected. This may be because the c.778G>T (p.Glu260Ter) allele with the premature stop variant results in the production of a smaller mRNA translated to a smaller protein detected at 30 kd. It is proposed that the second allele carrying the missense variant (c.260T>C) probably leads to an abnormal splicing event with an aberrant mRNA and no protein translated [Schaefer et al 2014].


Gene structure. BBIP1 encodes BBSome-interacting protein 1 (BBIP1). The gene contains four exons and has a transcript of 2057 bp (NM_001195306.1).

Pathogenic variants. Mutation of BBIP1 may be associated with BBS based on the following: Scheidecker et al [2014] report on a patient fulfilling the clinical criteria for BBS including retinitis pigmentosa, obesity, renal dysfunction, and intellectual disability born to consanguineous parents. Exome sequencing identified a homozygous stop variant in BBIP1 c.173T>G (p.Leu58Ter). This variant is presumed pathogenic since no BBIP1 protein could be detected in fibroblasts from an affected individual and BBIP1 (p.Leu58Ter) is unable to associate with the BBSome subunit BBS4 in immortalized human embryonic kidney (HEK)293FT cells.

Normal gene product. The protein BBIP1 co-localizes with seven of the known BBS gene products to form the BBSome, a protein complex involving in trafficking signal receptors to and from the cilia.

Abnormal gene length product. No BBIP1 protein product was identified in the fibroblasts of the individual with BBS and a homozygous stop variant strongly supporting the pathogenicity of this allele [Scheidecker et al 2014].

IFT27 (BBS19)

See Tables A and B.


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Chapter Notes

Author History

Philip L Beales, BSc, MD, FRCP, FMedSci (2003-present)
Elizabeth Forsythe, MBBS, BMedSci, MRCPCH (2014-present)
Alison J Ross, PhD; University College London (2003-2009)
Aoife M Waters, MB BAO, BCh, MRCPI, MSc; University College London (2009-2014)

Revision History

  • 23 April 2015 (aa) Revision: addition of IFT27 (BBS19); edits to Tables 1a, 1b
  • 20 February 2014 (me) Comprehensive update posted live
  • 29 September 2011 (cd) Revision: mutations in WDPCP (BBS15) and SDCCAG8 (BBS16) possibly associated with BBS
  • 18 November 2010 (cd) Revision: deletion/duplication analysis available for BBS4, BBS5, BBS7, and BBS9; deletions/duplications have been reported. Deletion/duplication analysis available for BBS1, BBS2, ARL6, MKKS, TTC8, BBS10, TRIM32, BBS12, and MKS1; no deletions or duplications involving any of these genes as causative of Bardet-Biedl syndrome have been reported.
  • 22 July 2010 (cd) Revision: sequence analysis available clinically for all 14 BBS-related genes; targeted mutation analysis available clinically for 11/ 14 genes; prenatal testing available for most (13/14) BBS-related genes
  • 13 October 2009 (me) Comprehensive update posted live
  • 5 January 2007 (cd) Revision: BBS12 identified
  • 26 June 2006 (ca) Revision: BBS10 and TRIM32 identified as genes involved in BBS, testing for C91fsX95 mutation in BBS10 clinically available
  • 18 November 2005 (me) Comprehensive update posted live
  • 17 October 2003 (pb) Revision: change in test availability
  • 14 July 2003 (me) Review posted live
  • 22 January 2003 (pb) Original submission
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