Does Bardet-Biedl syndrome have a characteristic face?

Lorda‐Sánchez, Isabel

doi:10.1136/jmg.38.5.e14

Cited by 17 publications

(18 citation statements)

References 6 publications

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“…a long philtrum and thin upper lip." Lorda-Sanchez et al 83 came to similar conclusions with their analysis of the BBS face and added small mouth, malar hypoplasia (small cheek bones) and retrognathia to the facial characteristics. Figure 3 shows the typical facial appearance of children with BBS.…”

Section: Craniofacial Dysmorphologymentioning

confidence: 64%

“…67,83 In contrast to OFD1, the features are variable and subtle, and it often takes a trained dysmorphologist to accurately describe the face, even though there is often an obvious gestalt, or overall appearance. Beales et al 70 described the facies of patients with BBS as having: "deep-set eyes, hypertelorism, downward slanting palpebral fissures, a flat nasal bridge with anteverted nares .…”

Section: Craniofacial Dysmorphologymentioning

confidence: 99%

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The nonmotile ciliopathies

Tobin

Beales²

2009

Genetics in Medicine

188

168

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Over the last 5 years, disorders of nonmotile cilia have come of age and their study has contributed immeasurably to our understanding of cell biology and human genetics. This review summarizes the main features of the ciliopathies, their underlying genetics, and the functions of the proteins involved. We describe some of the key findings in the field, including new animal models, the role of ciliopathy proteins in signaling pathways and development, and the unusual genetics of these diseases. We also discuss the therapeutic potential for these diseases and finally, discuss important future work that will extend our understanding of this fascinating organelle and its associated pathologies. Genet Med 2009:11(6):386 -402.

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Section: Craniofacial Dysmorphologymentioning

confidence: 64%

Section: Craniofacial Dysmorphologymentioning

confidence: 99%

The nonmotile ciliopathies

Tobin

Beales²

2009

Genetics in Medicine

188

168

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“…[3] A characteristic facial phenotype comprising macrobrachycephaly, with short, narrow palpebral fissures, a long, shallow philtrum with thin upper lip and downturned corners of the mouth is described. [3,4] The clinical spectrum shows overlap with a number of other genetic disorders involving abnormalities of ciliogenesis, such as McKusick-Kaufman syndrome and Alström syndrome. [5] Additional reports have expanded both the ocular and systemic phenotype.…”

Section: To Prof Peter Beighton 'Do Genetics and See The World ' …mentioning

confidence: 99%

“…[10] Most of the genes code for proteins belonging to two functional groups. BBS 1,2,4,5,7,8 and 9 are responsible for the formation of a complex known as the BBSome, important in promoting ciliogenesis. BBS 6, 10 and 12 code for type II chaperonins, which contribute to assembly of the BBSome.…”

Section: To Prof Peter Beighton 'Do Genetics and See The World ' …mentioning

confidence: 99%

Bardet Biedl syndrome in South Africa: A single founder mutation

et al. 2016

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Background. Bardet Biedl syndrome (BBS) is a multisystem disorder characterised by obesity, polydactyly, intellectual disability and loss of vision due to a progressive retinopathy. Although typically a highly heterogeneous autosomal recessive disease, homozygosity for single mutation in BBS 10 has been identified in a significant number of affected individuals tested in South Africa (SA). Objectives. To delineate the ethnic distribution and clinical phenotype in a cohort of SA BBS patients with the K243IfsX15 mutation in BBS 10 and discuss the implications for genetic testing of and counselling for this disorder in SA.Method. This was a descriptive cross-sectional study collating clinical and laboratory data retrospectively in a genetically homogenous subgroup of BBS patients from SA. Results. A total of 76 patients from 74 families were tested. Homozygosity for the K243IfsX15 BBS 10 mutation was found in 50 families (67%) and heterozygosity for the same mutation in an additional two affected individuals. With the exception of one patient of mixed ancestry, all were black South Africans from different language groups. This is in keeping with the observation that BBS is more common in this ethnic group compared with white and coloured patients in SA, first made by Prof. Beighton nearly 3 decades ago. A subset of 15 patients available for detailed phenotyping confirmed consistency with well-described features of the disorder, with some overlap with other ciliopathies. The onset of visual impairment was early in our cohort, before the age of 8 years, cognitive impairment was significant, and renal and cardiac abnormalities were infrequently encountered. Conclusion. The high frequency of homozygosity for a single mutation in an ethnic subset of the SA population is strongly suggestive of a founder effect. This has allowed establishment of a diagnostic test with a high yield in our local population. Better understanding of the phenotype will improve earlier recognition of the disorder to allow for appropriate intervention. Testing can confirm but not negate a clinical diagnosis, and can permit carrier and prenatal testing in informative families.

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“…BBS4, BBS6, and BBS8 (investigated in this study) are expressed in ciliated epithelia and localize to the centrosome and basal bodies of ciliated cells (5)(6)(7). Subtle craniofacial abnormalities in patients have been reported (8)(9)(10). Among the many additional features of BBS is Hirschsprung's disease (HD), a disorder of the enteric nervous system (ENS) (11).…”

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confidence: 99%

Inhibition of neural crest migration underlies craniofacial dysmorphology and Hirschsprung's disease in Bardet–Biedl syndrome

Tobin¹,

Franco

Eichers

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

175

171

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Facial recognition is central to the diagnosis of many syndromes, and craniofacial patterns may reflect common etiologies. In the pleiotropic Bardet-Biedl syndrome (BBS), a primary ciliopathy with intraflagellar transport dysfunction, patients have a characteristic facial ''gestalt'' that dysmorphologists have found difficult to characterize. Here, we use dense surface modeling (DSM) to reveal that BBS patients and mouse mutants have mid-facial defects involving homologous neural crest-derived structures shared by zebrafish morphants. These defects of the craniofacial (CF) skeleton arise from aberrant cranial neural crest cell (NCC) migration. These effects are not confined to the craniofacial region, but vagal-derived NCCs fail to populate the enteric nervous system, culminating in disordered gut motility. Furthermore, morphants display hallmarks of disrupted Sonic Hedgehog (Shh) signaling from which NCCs take positional cues. We propose a model whereby Bbs proteins modulate NCC migration, contributing to craniofacial morphogenesis and development of the enteric nervous system. These migration defects also explain the association of Hirschsprung's disease (HD) with BBS. Moreover, this is a previously undescribed method of using characterization of facial dysmorphology as a basis for investigating the pathomechanism of CF development in dysmorphic syndromes.sonic hedgehog ͉ Wnt ͉ cilia ͉ cell migration R ecognition of the facial ''gestalt'' is central to diagnosis of many genetic disorders, but the great variability of features often hinders successful classification (1). Recently, noninvasive 3D surface imaging has characterized dysmorphology in syndromes (2, 3). None, however, has been used to either define subtle facial dysmorphism or aid investigation of mechanisms for craniofacial dysmorphology.Bardet-Biedl syndrome (BBS) causes retinal degeneration, postaxial polydactyly, obesity, renal dysfunction, and cognitive impairment. Twelve BBS genes (BBS1-BBS12) have been discovered, and pathogenesis lies in primary cilia dysfunction (4). BBS4, BBS6, and BBS8 (investigated in this study) are expressed in ciliated epithelia and localize to the centrosome and basal bodies of ciliated cells (5-7). Subtle craniofacial abnormalities in patients have been reported (8-10). Among the many additional features of BBS is Hirschsprung's disease (HD), a disorder of the enteric nervous system (ENS) (11).Streams of neural crest cells (NCCs) from the caudal brain form most of the craniofacial (CF) skeleton (see ref. 12 for review). Cranial NCCs (CNCC) follow defined paths to populate the frontonasal prominence and branchial arch mesenchyme. Here, they proliferate and differentiate into structures of the face and cranium. Sonic Hedgehog (Shh) expressed in the ventral brain and oral ectoderm is essential for the formation of most facial structures (12). Shh-deficient mice have severe loss of craniofacial bones, and, in humans, SHH mutations cause midline CF defects with holoprosencephaly (HPE) (12).The ENS regulates gastrointestina...

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Does Bardet-Biedl syndrome have a characteristic face?

Cited by 17 publications

References 6 publications

The nonmotile ciliopathies

The nonmotile ciliopathies

Bardet Biedl syndrome in South Africa: A single founder mutation

Inhibition of neural crest migration underlies craniofacial dysmorphology and Hirschsprung's disease in Bardet–Biedl syndrome

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