Ciliopathies are diseases of genetic origin that cause morphological and functional alterations in many parts of the body. In this article we will describe symptoms and causes of Bardet-Biedl syndromeOne of the most common ciliopathies, which causes progressive vision loss and kidney problems, among other problems.
What is Bardet-Biedl syndrome?
Bardet-Biedl syndrome is a type of ciliopathy, A group of genetic diseases involving alterations of the primary cilia of cells. Other common diseases include polycystic kidney disease, nephronoptysis, Joubert syndrome, congenital Leber’s amaurosis, orofaciodigital syndrome, suffocating thoracic dystrophy, and Alström syndrome.
Signs of ciliary disease include degeneration of retinal tissue, the presence of brain abnormalities, and the development of kidney disease. Obesity, diabetes and skeletal dysplasia (morphological abnormalities of bone cells) are also common consequences of genetic defects in the synthesis of ciliary proteins.
Bardet-Biedl syndrome affects approximately 1 in 150,000 people. Its specific manifestations vary from case to case due to the great genetic variability of the defects that cause this disease.
Causes of this disorder
So far they have identified at least 16 genes associated with Bardet-Biedl disease. In most cases, the alterations are caused by mutations in several of the genes involved; this varies the signs considerably. Defects in the MKS gene appear to give rise to particularly severe variants of the disease.
However, about a fifth of cases show no mutations in any of these genes, suggesting that in the future more people with the same signs and symptoms will be found.
These genetic defects cause the proteins that allow the synthesis and proper functioning of the primary cilia, structures that are found in different cells. This causes deformities and problems in the eyes, kidneys, face or genitals, among other parts of the body.
Bardet-Biedl syndrome is associated with McKusick-Kaufman, which is inherited by autosomal recessive inheritance and is characterized by the presence of postaxial polydactyly, congenital heart disease and hydrometrocolpos (cystic dilation of the vagina and uterus which causes fluid accumulation). The differential diagnosis between the two disorders can be complex.
Main symptoms and signs
Many alterations can appear as a result of eyelash defects. We will focus on the most characteristic and relevant, although we will mention most of them.
1. Dystrophy of the cones and rods (retinitis pigmentosa)
Retinitis or pigmentary retinopathy is one of the most characteristic signs of ciliopatías; it occurs in over 90% of cases. It involves gradual loss of vision which begins with poor visual acuity and night blindness and persists after childhood, in some cases leading to poor vision in adolescence or adulthood.
2. Postaxial polydactyly
Another key sign is the presence of an extra finger on the hands or feet, Which occurs in 69% of people with Bardet-Biedl syndrome. In some cases, the fingers are shorter than normal (brachydactyly) and / or are fused (syndactyly).
3. Obesity of the trunk
In more than 70% of cases, obesity occurs from the age of two or three years; it is common for them to develop hypertension, hypercholesterolemia and type 2 diabetes mellitus Consequently. This type of obesity is also considered a key sign.
4. Kidney problems
Bardet-Biedl syndrome increases the risk of various kidney diseases: polycystic kidney disease, kidney dysplasia, nephronoptysis (or tubular cystic disease), and focal segmental glomerulosclerosis. Sometimes there are also alterations in the lower part of the urinary tract, such as dysfunction of the bladder destroyer.
Hypogonadism consists of deficient production of sex hormones, Which prevents sexual characteristics from developing in a normative way. This disorder also causes infertility and is more common in men with the syndrome.
6. Developmental disorders
It is common for them to happen developmental delays, language, speech and motor skills, As well as cognitive deficits (usually moderate) due to ciliary dysfunction. These problems often lead to alterations of varying severity in learning, social interactions and self-management.
7. Other symptoms
There are many other symptoms and signs common in Bardet-Biedl syndrome, although they are not considered to be fundamental features of the disease. These include behavioral and psychological disturbances such as sudden outbursts of anger and lack of emotional maturity.
Changes in the size of the head and malformations of teeth and face, Especially in the nose area. Partial or complete loss of smell (anosmia) also occurs in some cases.
Hirschsprung’s disease commonly occurs as a result of Bardet-Biedl disease. It is a disorder of the large intestine that hinders intestinal transit causing constipation, diarrhea and vomiting. It can sometimes cause serious gastrointestinal problems, especially in the colon.
- Beales, P., Elcioglu, N., Woolf, A., Parker, D. and Flinter, F. (1999). New criteria to improve the diagnosis of Bardet-Biedl syndrome: results of a population survey. Journal of Medical Genetics, 36 (6): 437-46.
- Waters, AM and Beales, PL (2011). Ciliopathies: an expanding spectrum of diseases. Pediatric Nephrology, 26 (7): 1039-1056.