Ciliopathies are diseases of genetic origin that cause morphological and functional alterations in many parts of the body. In this article we will describe the symptoms and the causes of Bardet-Biedl’s syndrome , one of the most frequent ciliopathies, which provokes a loss of progressive vision and renal alterations, among other problems.

What is Bardet-Biedl’s syndrome?

Bardet-Biedl’s syndrome is a type of ciliopathy , a group of genetic disease that involves alterations in the primary cilia of the cells. Other common ciliopathies are the renal polycystic disease, the nefronoptisis, the syndrome of Joubert, the congenital amaurosis of Leber, the orofaciodigital syndrome, the asphyxiating thoracic dystrophy and the syndrome of Alström.

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 in bone cells) are also common consequences of genetic defects in the synthesis of ciliary proteins .

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Bardet-Biedl’s syndrome affects approximately 1 of every 150 thousand persons. Their specific manifestations vary in function of the case because of the great genetic variability of the defects that cause this disease.

Causes of this disorder

Up to the moment there have been identified at least 16 genes that are associated with Bardet-Biedl’s disease . In great part of the cases the alterations are caused by mutations in several of the implied genes; this causes that the signs vary a lot. The defects in the gene MKS seem to give place to especially serious variants of the disorder.

However, about one-fifth of cases have no mutations in any of these genes, suggesting that others will be found in the future to be related to the same signs and symptoms.

These genetic defects make the proteins that allow the synthesis and proper functioning of the primary cilia, structures that are found in different cells. This causes malformations and problems in the eyes, kidneys, face or genitals, among other parts of the body.

Bardet-Biedl’s syndrome is associated with that of McKusick-Kaufman, which is transmitted by inheritance autosomal recessive and it is characterized by the presence of polydactylia postaxial, congenital cardiopathy and hidrometrocolpos (cystic dilation of the vagina and of the uterus that causes accumulation of fluids). The differential diagnosis between the two disorders can be complex.

Main symptoms and signs

There are many alterations that can appear as a result of defects in the cilia. We will focus on the most characteristic and relevant ones, although we will mention most of the

1. Cone and stick dystrophy (retinitis pigmentosa)

Retinitis or retinopathy of pigment is one of the most characteristic signs of ciliary diseases; it occurs in more than 90% of cases. It involves a progressive loss of vision that begins with a lack of visual acuity and night blindness and is maintained after childhood, in some cases reaching a lack of vision in adolescence or adulthood.

2. Post-tax polydactyly

Another of the key signs is the presence of a finger additional in the hands or in the feet , which occurs in 69 % of the persons with Bardet-Biedl’s syndrome. In some cases the fingers are shorter than normal (brachidactyly) and/or they are fused between them (syndactyly).

3. Trunk obesity

In more than 70% of the cases, obesity occurs from the age of two or three; it is common for hypertension, hypercholesterolemia and type 2 diabetes mellitus to develop as a consequence. This type of obesity is also considered a key sign.

4. Renal disorders

Bardet-Biedl’s syndrome increases the risk of suffering diverse diseases of the kidneys: polycystic kidneys, renal dysplasia, nephronoptisis (or tubular cystic disease) and focal segmental glomerulosclerosis. Sometimes alterations in the lower part of the urinary tract also appear, such as dysfunctions of the detrusor of the bladder.

5. Hypogonadism

Hypogonadism consists of the deficient production of sex hormones , which causes sexual characteristics not to develop in a normative way. This alteration also causes sterility and is more frequent in males with the syndrome.

6. Developmental disorders

It is common for developmental delays in language, speech and motor skills to occur, as well as cognitive deficits (generally moderate) as a result of ciliary dysfunctions. These problems usually cause alterations of varying severity in learning, social interaction and self-management.

7. Other symptoms

Many other symptoms and frequent signs exist in Bardet-Biedl’s syndrome, though they are not considered to be fundamental characteristics of the disease. Among these we find behavioural and psychological alterations as sudden attacks of anger and lack of emotional maturity.

Alterations in the size of the head and malformations in the teeth and face are common, especially in the nose area. Partial or total loss of smell (anosmia) also appears in some cases.

The disease of Hirschsprung appears frequently as consequence of that of Bardet-Biedl. It is a disorder of the big intestine that hinders the intestinal traffic causing constipation, diarrhea and vomits. Sometimes it can provoke severe gastrointestinal problems, especially in the colon.

Bibliographic references:

  • Beales, P., Elcioglu, N., Woolf, A., Parker, D. & Flinter, F. (1999). New criteria for improved diagnosis of Bardet-Biedl syndrome: results of a population survey. Journal of Medical Genetics, 36(6): 437-46.
  • Waters, A. M. & Beales, P. L. (2011). Ciliopathies: an expanding disease spectrum. Pediatric Nephrology, 26(7): 1039-1056.