Antenatal presentation of Bardet-Biedl syndrome may mimic Meckel syndrome

Area of Science:

• Medical Genetics
• Developmental Biology
• Clinical Dysmorphology

Background:

• Bardet-Biedl syndrome (BBS) is a complex genetic disorder with diverse clinical manifestations including obesity, retinal dystrophy, and organ dysfunction.
• Antenatal diagnosis of BBS is challenging due to overlapping features with other genetic syndromes, notably Meckel syndrome.
• Genetic heterogeneity of BBS involves at least eight genes, with BBS1 mutations accounting for a significant proportion of cases.

Purpose of the Study:

• To investigate the genetic basis of Bardet-Biedl syndrome in fetuses presenting with features overlapping with Meckel syndrome.
• To determine the frequency of Bardet-Biedl syndrome gene mutations in a cohort of antenatal cases with cystic kidneys and polydactyly or hepatic fibrosis.

Main Methods:

• Sequencing of eight known Bardet-Biedl syndrome genes (BBS1-BBS8).
• Analysis of 13 fetal cases with antenatal diagnoses of Meckel or Meckel-like syndrome, characterized by cystic kidneys and polydactyly and/or hepatic fibrosis.
• Genotyping for mutations in BBS genes.

Main Results:

• Recessive mutations in BBS genes were identified in six of the 13 fetuses (BBS2, BBS4, BBS6).
• Heterozygous BBS6 mutations were found in three additional cases.
• No mutations were detected in BBS1, BBS3, BBS5, BBS7, or BBS8 genes in this cohort.

Conclusions:

• The antenatal presentation of Bardet-Biedl syndrome can closely mimic Meckel syndrome.
• Genetic testing for BBS genes is crucial in the differential diagnosis of fetuses with cystic kidneys, polydactyly, and/or hepatic fibrosis.
• This study highlights the importance of considering BBS in the prenatal evaluation of specific dysmorphic features.