2. Epidemiology and key points
Autosomal recessive ciliopathy.
The estimated incidence is 1:160 000 in northern European populations and 1:13 500 in
some Arab populations, more common in the Bedouin population of Kuwait and on the
island of Newfoundland
North American population 1:140,000
Characterised by retinal dystrophy, renal dysfunction, post-axial polydactyly, obesity,
cognitive deficit and hypogenitalism.
Diagnosis is based on clinical features.
Molecular genetic testing is available and currently 16 genes are known to be
associated with Bardet–Biedl syndrome (BBS), accounting for approximately 80% of
clinically diagnosed BBS.
Surveillance includes regular ophthalmological evaluation, montoring of renal, liver,
glucose, lipid and endocrine profile and regular weight and blood pressure
measurements.
3. LMBBS or BBS ?
BBS is named after Georges Bardet and Arthur Biedl. The first known case was
reported by Laurence and Moon in 1866.
Laurence-Moon-Biedl-Bardet syndrome (LMBBS) is no longer considered as a valid
term as patients of Laurence and Moon had paraplegia but no polydactyly and
obesity, which are the key elements of the BBS.
Hence, Laurence-Moon syndrome is usually considered a separate entity. However,
some recent research suggests that the two conditions may not be distinct.
4. BBS Clinical Features
Eyes: Pigmentary retinopathy, poor visual acuity, low vision,
and/or blindness caused by an impaired photoreceptor transport mechanism in
the retina.
Nose: Loss of, or reduced sense of, smell. (anosmia). Some patients claim extra-sensitive
sense of smell.
Hand and foot: Polydactyly (extra digits) or syndactyly (webbing of fingers and
toes).
Cardiovascular system: Hypertrophy of interventricular septum and left ventricle,
Hypertension and dilated cardiomyopathy.
5. Gastrointestinal system: Fibrosis.
Urogenital system: Hypogonadism, renal failure, urogenital sinuses, ectopic
urethra, uterus duplex, septate vagina, and hypoplasia of the uterus, ovaries,
and fallopian tubes.
Growth and development: Developmental Delay, especially of fine and gross motor
skills
Behavior: a wide variety of socialization and social interaction problems have been
identified with BBS.
learning difficulties (may or may not be mental retardation)
Diabetes, in some cases.
Dyslipidemia, in some cases.
6. Defective thermosensation or mechanosensation.
Additional features: Obesity, possibly related to a decreased sensory function that
would normally indicate satiation. Hyperphagia in some patients.
7. Pathophysiology
The detailed biochemical mechanism that leads to BBS is still unclear.
The gene products encoded by these BBS genes, called BBS proteins, are located in
the basal body and cilia of the cell.
Using the round wormC. elegans as a model system, biologists found that BBS
proteins are involved in a process called Intraflagellar transport (IFT), a bi-directional
transportation activity within the cilia along the long axis of the ciliary
shaft that is essential for ciliogenesis and the maintenance of cilia. Recent
biochemical analysis of human BBS proteins revealed that BBS proteins are
assembled into a multiple protein complex, called "BBSome". BBSome is proposed
to be responsible for transporting intracellular vesicles to the base of the cilia and
to play an important role in the ciliary function.
8. Since abnormalities of cilia are known to be related to a wide range of disease
symptoms including those commonly seen in BBS patients, it is now widely
accepted that mutated BBS genes affect normal cilia functions, which, in turns,
causes BBS
A theory that photoreceptor cells are nourished by the IFT of retinal cilia now offers
a potential explanation for the retinal dystrophy common in BBS patients after their
early years of life
BBsome: BBS1, BBS2, ARL6/BBS3, BBS4, BBS5, BBS7, TTC8/BBS8, BBS10, TRIM32/BB
S11 BBS12, CCDC28B, CEP290, TMEM67, MKS1, MKKS
Autosomal Recessive Ciliopathy.
9. Other forms of ciliopathies
Other known ciliopathies include
primary ciliary dyskinesia,
polycystic kidney and
nephronophthisis,
Alstrom syndrome,
Meckel–Gruber syndrome
and some forms of retinal degeneration
