Bardet-Biedl Syndrome

Carriers for Bardet-Biedl syndrome (those with one mutation but are unaffected by the condition) should ask parents and siblings to consider getting tested. Those with children or who are planning to have children should also ask their partners about testing for a mutation linked to Bardet-Biedl syndrome. If two would-be parents are carriers, each pregnancy carries a 25% risk for Bardet-Biedl syndrome.
Those with Bardet-Biedl syndrome should suggest that their parents and siblings get tested; their parents are most likely carriers for Bardet-Biedl syndrome, which means further that their siblings have a 50% chance of also being carriers. Someone with Bardet-Biedl syndrome with children or planning to have children should ask her partner about testing: if her partner is not a carrier, each child would be a carrier; if her partner is a carrier for Bardet-Biedl syndrome, each child would have a 50% risk of being a carrier and a 50% risk of inheriting Bardet-Biedl syndrome; if her partner also has Bardet-Biedl syndrome, each child would inherit Bardet-Biedl syndrome. Importantly, though, carrier testing cannot identify all mutations that case Bardet-Biedl syndrome.

The Bardet-Biedl Syndrome Family Association connects families and people with Bardet-Biedl syndrome. After asking people about their specific genetic mutation, a user can be connected with someone who has Bardet-Biedl syndrome or family members of those affected.
They can be contacted at their website http://www.bardetbiedl.org/ or through their Facebook page: https://www.facebook.com/BardetBiedlSyndromeFamilyAssociation/.
A young lady named Kaylin has been very open about her diagnosis and about living with her vision loss. There was an article written about her (https://globalgenes.org/raredaily/bardet-biedl-syndrome-robs-13-year-old-kaylin-of-her-vision-but-not-her-spirit/) with a link to her Facebook page if you wish to contact her.
A patient may also ask one’s doctor whether she knows of any person or families willing to meet and talk about the condition.

For parents and families of children with genetic diseases like Bardet-Biedl syndrome, all states have a Parent Training and Information Center (PTI) offering information on early interventions, school services, therapy, local policies, transportation and more. Some states also have Community Parent Resources Centers that offer similar support. More information on both and a map of the different states and their services can be found at http://www.parentcenterhub.org/find-your-center/.

Specialists whom those with Bardet-Biedl syndrome should see include:

Bardet-Biedl syndrome is usually abbreviated BBS.
“BBS1-related” indicates that Bardet-Biedl syndrome is caused by a change in the BBS1 gene.

Bardet-Biedl syndrome is a genetic disorder that affects many different body systems; it is known to cause progressive vision loss, extra fingers and/or toes, obesity, underdeveloped gonads—which can lead to infertility—kidney problems, and learning problems.

The main health problems in people with Bardet-Biedl syndrome are vision loss and poor kidney function. Vision loss is progressive, usually beginning as night blindness around 7-8 years. More than anything else, poor kidney function causes death in people with Bardet-Biedl syndrome, and so should be monitored carefully. Additional health problems include genital and urinary malformation, and hormone-induced obesity and infertility.

Mutations in the BBS1 gene produce shorter versions of a particular protein. This atypical protein affects the function of the cilia, hair-like tubules that extend outside cells in the body. Cilia help cells move and communicate between each other; when these cilia cannot function effectively, neither can the cells’ movement and communication. Researchers believe this dysfunction causes many symptoms of Bardet-Biedl syndrome including vision loss, kidney problems, lack of smell and hearing loss.

Over 30 different mutations are known to cause Bardet-Biedl syndrome. About 25% of all cases of Bardet-Biedl syndrome are caused by genetic changes in the BBS1 gene, located on chromosome 11 at q13.

Bardet-Biedl syndrome is typically diagnosed clinically. Genetic testing is used both to supplement an unclear clinical presentation and for family planning. If an individual is clinically diagnosed with Bardet-Biedl syndrome and afterward receives a variant of uncertain significance on their genetic test, she is not freed from her diagnosis—she should still be treated for Bardet-Biedl syndrome. However, the discussion about family planning may be unclear because the providers are not sure if the variant is causing Bardet-Biedl syndrome or if there is a different cause not picked up by the test (about 20-30% of people with Bardet-Biedl syndrome have negative genetic testing). Testing other family members may be recommended to help determine whether or not the variant appears disease-causing. Some reported cases of Bardet-Biedl syndrome involve three mutations rather than the usual two, which is called triallelic.

Main symptoms of Bardet-Biedl syndrome are vision problems (rod-cone dystrophy), obesity (which may cause diabetes mellitus and/or high blood pressure), extra fingers or toes (postaxial polydactyly), cognitive impairment, learning difficulties, reduced size of testes and fertility in males (due to male hypogonadotropic hypogonadism), malformations of females’ genital and urinary organs, and kidney abnormalities. Typically, due to the rod-cone dystrophy, people with Bardet-Biedl syndrome have night blindness which starts around 7-8 years of age; most are legally blind by 15-16 years of age.
Less common and more variable symptoms include impaired speech, delayed motor skills (e.g. walking), behavioral problems, clumsiness (ataxia), ear infections, hearing loss, asthma and partial or complete loss of smell (anosmia). Some individuals have reported issues with the heart, liver, and digestive system.
Specific physical features can include dental (teeth) abnormalities, short fingers and/or toes, wide-spaced eyes, flat nasal (nose) bridge, flared nostrils, a long groove above the center of the lip (philtrum), and downward-slanting eyelid folds (palpebral fissures).

Cilia project from the cells of the body. Of the two types of cilia, motile cilia help cells move and primary cilia permit intercellular communication. Primary cilia inform other cells of their activity and advise how these others should function. With Bardet-Biedl syndrome, however, cilia often send faulty messages and often cannot sent the necessary messages at all.

Treating any genetic condition like Bardet-Biedl syndrome is a marathon and not a sprint; not everything can be handled right away, and it is important to celebrate the milestones. The first order of business is addressing any of a child’s immediate medical problem with a doctor. Afterward one should have a child evaluated for developmental and speech delays; knowing the specific services a child requires will help parents guide their child toward the growth they need to improve on those delays. Speech, physical, occupational and vision therapies may assist a child in this process. Furthermore, a child’s parents should speak with her school’s teachers and administrators to best accommodate her needs.

People with Bardet-Biedl syndrome may or may not express all of the symptoms associated with their condition. There is variability, even among family members, regarding both which symptoms are expressed and how severe these symptoms are. The main symptoms, exhibited by most people with Bardet-Biedl syndrome, are vision loss, extra fingers and/or toes, obesity, kidney problems and learning difficulties. However, other symptoms, such as intellectual disability, genital and urinary abnormalities, infertility, speech impairment, and behavioral abnormalities are more variable and may not expressed in an individual with Bardet-Biedl syndrome.

Screening with a second-trimester ultrasound can reveal the anomalies typical of Bardet-Biedl syndrome, such as polydactyly and renal abnormalities. However, ultrasound cannot definitively rule out a diagnosis, as not all Bardet-Biedl babies will have these findings. If the familial mutations are already known, prenatal genetic testing may be performed through chorionic villi sampling (CVS) or an amniocentesis.

For a clinical diagnosis a doctor may order a kidney ultrasound to check for any malformations. For a vision test, a doctor (or ophthalmologist) may order an electroretinogram (ERG) to measure the response of eyes to light. When pursuing genetic testing, sequence analysis detects the majority of genetic changes and a genetic panel (looking at multiple genes associated with Bardet-Biedl syndrome, not just BBS1) will likely be ordered. A doctor may order targeted testing when a patient knows of a family member with a mutation associated with Bardet-Biedl syndrome in order to examine the specific gene mutated in the relative.

At ClinicalTrials.gov is a list of research trials—completed and recruiting—related to Bardet-Biedl syndrome. If the link does not work, one may search Bardet-Biedl syndrome at www.clinicaltrials.gov to find related studies.
As of February 2016 there were four studies still recruiting people with Bardet-Biedl syndrome.

There is currently no treatment for the mutations causing Bardet-Biedl syndrome; current treatment plans for Bardet-Biedl syndrome address its symptoms.
Due to the progressive vision loss, visual aids and educational programs specific to people with visual impairments are recommended.
For obesity, diet and exercise are recommended; medication used for the general population may also be used if hypertension or diabetes mellitus is a concern.
If the person with Bardet-Biedl syndrome has behavioral problems, behavioral therapies for them and their parents may be recommended. Behavioral therapies may also assist with obesity.
Early interventions and special education may benefit the child in the long run, especially to prepare for the loss of vision. Additionally, speech therapy will help those with delayed and impaired speech.
Surgery may be possible to correct genital or urinary malformations and for the extra fingers and/or toes.
Hormone replacement may help males with hypogonadism (small testes).
While infertility is a problem for many with Bardet-Biedl syndrome, it is not universal; contraceptives should still be discussed for those affected and interested in sexual relationships.

Bardet-Biedl syndrome causes vision loss, kidney problems, obesity, extra fingers and/or toes, and genital and/or urinary abnormalities. Individuals with Bardet-Biedl syndrome are also more likely to have intellectual disability. Learning difficulties caused by Bardet-Biedl syndrome are exacerbated by vision loss and intellectual disability.

Doctors should be aware of all medications those affected are using to treat their symptoms and that they should not take medications contraindicated for people with kidney impairments. By virtue of the large number of specialists whom someone with Bardet-Biedl should see, it is important that all each doctor be informed of the other tests, results, and follow-ups ordered by each specialist.

Research does not yet know a clear correlation between the different genes mutated and the symptoms caused, or their severity. Whether an individual has a mutation in, for example, the BBS1 gene or the BBS10 gene, she will show Bardet-Biedl syndrome. Some research suggests that people with a mutation in BBS1 show less severe eye symptoms and that people with a mutation in BBS10 are more resistant to insulin (and thereby have a higher risk of obesity). However, larger studies have not confirmed these relations between specific mutations and specific symptoms.

Bardet-Biedl syndrome is most often inherited in an autosomal recessive fashion. Typical humans have 23 pairs of chromosomes, receiving one chromosome (containing many genes) of each pair from each parent (for a total of 46). Autosomal recessive conditions affect individuals with a mutation in both copies of a gene pair. For a person to have Bardet-Biedl syndrome, she must have a mutation in both copies of the gene. A person with a mutation in only one gene is called a carrier: while she is not affected by Bardet-Biedl syndrome, she can pass the mutation to her children. For each pregnancy with two carriers as parents, there is a 25% chance of having a child with Bardet-Biedl syndrome, a 50% chance of having a child who is also a carrier, and a 25% of having a child who is neither a carrier nor affected by Bardet-Biedl syndrome.

Bardet-Biedl syndrome is typically clinically diagnosed in childhood by identifying its characteristic presentations (ex. extra fingers and/or toes, obesity, vision problems). An ophthalmologist may diagnose it with an electroretinogram (ERG), measuring the eyes’ response to light.
For a clinical diagnosis a person either needs to present with 4 primary features or 3 primary and 2 secondary features.

Primary features

The lifespan for people with Bardet-Biedl syndrome varies, in large part depending on the severity of their symptoms and how well these are managed. Bardet-Biedl syndrome does increase the risk for early death, primarily due to kidney disease.

There is a national support group for Bardet-Biedl syndrome (http://www.bardetbiedl.org/). In the case that one wishes to start a local chapter or support group, one may contact the national group to ask for support and suggestions for starting, or about how they themselves got started and whether they have contacts nearby. Getting in touch with local doctors and service workers may also help to network with affected individuals and families in one’s area; they may also may have suggestions for referrals or other medical information people may want or need.

Go online to visit the Bardet-Biedl syndrome association foundation to donate. Donations will go towards supporting research in treatment and care and education and outreach to families, physicians, and educators. Its page is found at http://www.bardetbiedl.org/donate/.

Diagnosis is generally made in late childhood or early adulthood. Generally, Bardet-Biedl syndrome is first suspected when vision worsens around 7-8 years of age. When suspicious that a child has Bardet-Biedl syndrome, talking to a doctor about a referral to ophthalmology (eye doctor) is strongly recommended. A test that ophthalmologists can use to check for vision loss is done with an electroretinogram (ERG); it should be noted that significant changes in vision are usually not seen in people with Bardet-Biedl syndrome before five years of age.

One well-known center of excellence for Bardet-Biedl syndrome is Marshfield Clinic in Marshfield, WI. Its website has information on the clinic as well as other resources: https://www.marshfieldclinic.org/services/bardet-biedl-syndrome-(bbs).
If one is unable to travel to the Marshfield Clinic, nearby clinics and specialists may be researched online and sought out by talking with one’s doctor; also helpful is getting in touch with nearby families with a child or family member with Bardet-Biedl syndrome (http://www.bardetbiedl.org/).
More information on finding specialists for rare diseases can be found at the Genetic and Rare Diseases Information Center (GARD): https://rarediseases.info.nih.gov/gard/pages/25/how-to-find-a-disease-specialist.

Bardet-Biedl syndrome occurs in one out of between 140,000 and 160,000 newborns in North America and Europe. Bardet-Biedl syndrome is more common in Newfoundland (located off the east coast of Canada), occurring in about 1/17,000 newborns. Bardet-Biedl syndrome is also more common in Kuwait, specifically among the Bedouin population, occurring in about 1/13,500 newborns. Approximately 25%-30% of all cases of Bardet-Biedl syndrome are Bardet-Biedl syndrome (BBS1-related).

Approximately 33% of people with Bardet-Biedl syndrome have some form of behavioral problem. Managing these behaviors should be handled on an individual basis and therapies should target their specific presentation. Some common behavioral problems include depression, temper tantrums, misreading social cues, obsessive compulsive behavior, inattention and emotional immaturity. Early interventions and behavioral therapies may help.

The lab running the test will determine the sample type; Bardet-Biedl syndrome should not affect which sample type (blood or saliva) will work best. A biopsy should not be needed for a genetic test for Bardet-Biedl syndrome.

While all people with Bardet-Biedl syndrome experience some vision loss, the degree and progression among them may differ. Some may be considered legally blind by their teens, others may live until middle age before facing this blindness. Despite this blindness, those affected tend to retain some degree of light sensitivity. Due to the way the retina degenerates, most with Bardet-Biedl syndrome begin losing their sight in dim light (night blindness), losing the acuity of their color vision, or losing their peripheral vision. Others may experience uncontrolled eye movements (nystagmus), eyes looking in different directions (strabismus), the eyeball becoming too long (high myopia), glaucoma and cataracts.

People with Bardet-Biedl syndrome should avoid substances contraindicated (not recommended) for those with kidney impairment.

Most men with Bardet-Biedl syndrome do not produce enough sex hormones to have children. However, men with Bardet-Biedl have fathered children in at least two reported cases.

No current treatment delays or prevents the progressive vision loss characteristic of Bardet-Biedl syndrome. Kidney dysfunction and malformations should be treated for their specific problems; a kidney transplant may be required, something the patient’s doctor should evaluate and recommend when appropriate. Cardiac abnormalities in a person with Bardet-Biedl syndrome can be treated as they would in a member of the general population. People with Bardet-Biedl syndrome should avoid also substances that are contraindicated (not recommended) for those with kidney impairment.

Other names for Bardet-Biedl syndrome include Bardet-Biedl syndrome and (less commonly) Laurence-Moon-Bardet-Biedl syndrome.

Approximately 70% of people with Bardet-Biedl syndrome have extra fingers and/or toes near their pinkie fingers or pinkie toes (postaxial polydactyly). Vision loss in people with Bardet-Biedl syndrome, while nearly universal, is progressive and may not be present at birth. The extra fingers and/or toes may therefore be the first indication of Bardet-Biedl syndrome.

The Bardet-Biedl Syndrome Family Association has information on what Bardet-Biedl syndrome is, ongoing research, and upcoming conferences. In addition, they provide a newsletter to connect families and keep them up-to-date on research and options for treatment of and therapy for Bardet-Biedl syndrome. They also have a Facebook page: https://www.facebook.com/BardetBiedlSyndromeFamilyAssociation/.

Bardet-Biedl syndrome has no specific earlier, later, or variant forms. However, the symptoms of Bardet-Biedl syndrome vary greatly, as does the severity of those symptoms, and even within the same family. Most afflicted with Bardet-Biedl syndrome exhibit vision loss, extra fingers and/or toes, obesity, kidney problems, and learning difficulties. Other symptoms, such as intellectual disability, genital and urinary abnormalities, infertility, speech impairment and behavioral abnormalities, are expressed in different ways—or are not expressed at all—across individuals with Bardet-Biedl syndrome.

Bardet-Biedl syndrome also overlaps with Laurence-Moon syndrome (LMS), so much so that the two were once thought to be the same condition, and were called Laurence-Moon-Bardet-Biedl syndrome (LMBBS). However, differences between the two conditions were noted in the 1980s and each now has its own diagnosis. Nevertheless, some individuals with LMS show genetic mutations in genes related to Bardet-Biedl syndrome, and lines between the conditions remain blurred.
Alstrom syndrome is characterized by vision and hearing abnormalities, childhood obesity, diabetes mellitus and progressive kidney dysfunction. Additional findings may include involuntary eye movements (nystagmus), heart disease, and skin abnormalities. Intelligence is not typically affected and extra fingers and toes are not associated with this condition.
Meckel syndrome (also called Meckel-Gruber syndrome) is characterized by a part of the brain protruding through the front or back of the skull (encephalocele), extra fingers and/or toes, multiple cysts in the kidneys, liver scarring, underdeveloped lungs and genital abnormalities. Mutations in some of the Bardet-Biedl syndrome genes—though not BBS1—have been found in people with Meckel syndrome.
McKusick-Kaufman syndrome (MKKS) is extremely rare and characterized by extra fingers and/or toes, heart defects, water fluid in the uterus and vagina (hydrometrocolpos), genital and urinary malformations, underdeveloped lungs, gastrointestinal abnormalities and kidney problems. The mutation associated with MKKS is called BBS6 and is also associated with Bardet-Biedl syndrome.
Biemond II syndrome is also extremely rare and is characterized by lacking part of the colored portion of the eye (the iris coloboma), intellectual disability, obesity, genital and urinary abnormalities and extra fingers and/or toes. No genes are yet identified with this syndrome.
Prader-Willi syndrome is characterized by low muscle tone (hypotonia), feeding difficulties in infancy, obesity later in life, genital abnormalities, intellectual disability and behavioral problems.