Antenatal Presentation of Bardet-Biedl Syndrome May Mimic Meckel Syndrome

Abstract

Bardet-Biedl syndrome (BBS) is a multisystemic disorder characterized by postaxial polydactyly, progressive retinal dystrophy, obesity, hypogonadism, renal dysfunction, and learning difficulty. Other manifestations include diabetes mellitus, heart disease, hepatic fibrosis, and neurological features. The condition is genetically heterogeneous, and eight genes (BBS1-BBS8) have been identified to date. A mutation of the BBS1 gene on chromosome 11q13 is observed in 30%-40% of BBS cases. In addition, a complex triallelic inheritance has been established in this disorder--that is, in some families, three mutations at two BBS loci are necessary for the disease to be expressed. The clinical features of BBS that can be observed at birth are polydactyly, kidney anomaly, hepatic fibrosis, and genital and heart malformations. Interestingly, polydactyly, cystic kidneys, and liver anomalies (hepatic fibrosis with bile-duct proliferation) are also observed in Meckel syndrome, along with occipital encephalocele. Therefore, we decided to sequence the eight BBS genes in a series of 13 antenatal cases presenting with cystic kidneys and polydactyly and/or hepatic fibrosis but no encephalocele. These fetuses were mostly diagnosed as having Meckel or "Meckel-like" syndrome. In six cases, we identified a recessive mutation in a BBS gene (three in BBS2, two in BBS4, and one in BBS6). We found a heterozygous BBS6 mutation in three additional cases. No BBS1, BBS3, BBS5, BBS7, or BBS8 mutations were identified in our series. These results suggest that the antenatal presentation of BBS may mimic Meckel syndrome.

Spectrum ofMKS1andMKS3mutations in Meckel syndrome: a genotype-phenotype correlation

“…However, we failed to find any MKS gene mutations in the fetal BBS cases previously reported (Karmous-Benailly, et al, 2005). Also, we did not find a combination of mutations in both MKS1 and MKS3 genes in the same patient.…”

“…This condition is also genetically heterogeneous, with 12 genes identified to date (BBS1-BBS12). Although kidney histopathological findings were similar in BBS and MKS, bile duct proliferation of liver was not observed in BBS cases (Karmous-Benailly, et al, 2005). In one case with Dandy-Walker malformation, MKS cystic kidneys and polydactyly, but no bile duct proliferation, we identified BBS2 gene mutations (Karmous-Benailly, et al, 2005).…”

“…Whilst all had cystic dysplasia of the kidney as an obligatory feature, 63% had an occipital meningocele, and 18% had no reported brain malformation (Fraser and Lytwyn, 1981). We have recently shown a phenotypic overlap of Meckel and Bardet-Biedl syndrome, another multisystemic genetic disorder characterized by postaxial polydactyly, progressive retinal dystrophy, obesity, hypogonadism, learning difficulties and renal dysfunction (Karmous-Benailly, et al, 2005). This condition is also genetically heterogeneous, with 12 genes identified to date (BBS1-BBS12).…”

Bardet–Biedl syndrome

“…37 For example, mutations in BBS2, BBS4 and BBS6 have been identified in patients with Meckel syndrome. 38 Similarly, mutations in MKS1, which normally lead to Meckel syndrome, may be associated with a BBS phenotype and mutations in MKS3 have been identified in patients with BBS and Joubert syndrome. 39 It appears that the ciliopathy phenotype reflects both the specific mutated loci and the total mutational load.…”

Small organelle, big responsibility: the role of centrosomes in development and disease

“…In humans, BBS4 mutations cause BBS characterized by retinal dystrophy, obesity, cognitive impairments and renal malformation [140]. BBS4 mutations are also present in the embryonically lethal Meckel syndrome [141]. Likewise, CEP290 mutations have been linked to both BBS and Meckel, in addition to Senior-Loken and Joubert syndromes [142].…”