- Laurence-Moon-Biedl syndrome and Laurence-Moon-Biedl-Bardet redirect here. See below for an explanation.
The Bardet-Biedl syndrome
is a ciliopathic human genetic disorder
that produces many effects
and affects many body systems. It is characterized pricipally by obesity
, retinitis pigmentosa
, mental retardation
, and renal failure
in some cases.
Eponym and classification
The syndrome is named after Georges Bardet
and Arthur Biedl
Two forms have been identified:
The first known case was reported by Laurence and Moon in 1866 at the Ophthalmic Hospital in South London. Laurence-Moon-Biedl-Bardet syndrome are no longer considered as valid terms in that patients of Laurence and Moon had paraplegia but no polydactyly and obesity which are the key elements of the Bardet-Biedl the syndrome. Laurence-Moon syndrome is usually considered a separate entity. However, some recent research suggests that the two conditions may not be distinct.
Major clinical features
- Eyes: Pigmentary retinopathy, poor visual acuity, low vision, and/or blindness.
- 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 and dilated cardiomyopathy.
- 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: Mental and growth retardation.
- Behavior and performance: a wide variety of socialization and social interaction problems have been identified with BBS. Some refer to it as a kind of "mild-Autism." Many children who are later (explicitly and formally) diagnosed with the syndrome have gone through an extended period of time where school and medical professionals have struggled to find a name for the child's problems over several years.
- Defective thermosensation or mechanosensation. New finding reported in October 2007: "hitherto unrecognized, but essential, role for mammalian basal body proteins in the acquisition of mechano- and thermosensory stimuli [highlight potential] clinical features of ciliopathies in humans.
- Additional features: Obesity, possibly related to a decreased sensory function that would normally indicate satiation.
The detailed biochemical mechanism that leads to BBS is still unclear. At this moment, twelve genes (BBS1
) that are responsible for the disease when mutated, have been cloned. The gene products encoded by these BBS
genes, called BBS proteins, are located in the basal body
of the cell.
Using the round worm C. 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 are essential for the formation and 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 roles in the ciliary function. 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, cause BBS.
Relation to other rare genetic disorders
Recent findings in genetic research have suggested that a large number of genetic disorders, both genetic syndromes and genetic diseases, that were not previously identified in the medical literature as related, may be, in fact, highly related in the genetypical root cause of the widely-varying, phenotypically-observed disorders. BBS is one such syndrome that has now been identified to be caused by defects in the cellular ciliary structure. Thus, BBS is a ciliopathy. Other known ciliopathies include primary ciliary dyskinesia, polycystic kidney and liver disease, nephronophthisis, Alstrom syndrome, Meckel-Gruber syndrome and some forms of retinal degeneration.
The syndrome is familial and is transmitted as an autosomal recessive
trait. chromosome 3
locus appears to be linked to polydactyly
of all four limbs, whereas chromosome 15
is associated with early-onset morbid obesity
and is mostly confined to the hands, and chromosome 16
represents the "leanest" form.