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Case Reports
. 2022 May;10(5):e1869.
doi: 10.1002/mgg3.1869. Epub 2022 Mar 23.

Atypical phenotype of a patient with Bardet-Biedl syndrome type 4

Natacha Sloboda  1 , Laetitia Lambert  1 , Viorica Ciorna  2 , Ange-Line Bruel  3 , Frédéric Tran Mau-Them  3   4 , Vladimir Gomola  5 , Jean-Louis Lemelle  5 , Olivier Klein  6 , Marie-Christine Camoin-Schweitzer  7 , Marie Magnavacca  7 , Carole Legagneur  8 , Marie-Laure Ezsto  9 , Céline Bonnet  10 , Christophe Philippe  3   4 , Bruno Leheup  1
Affiliations
Case Reports

Atypical phenotype of a patient with Bardet-Biedl syndrome type 4

Natacha Sloboda et al. Mol Genet Genomic Med. 2022 May.

Abstract

Background: Bardet-Biedl syndrome (BBS) is a multisystemic disorder characterized by rod-cone dystrophy, truncal obesity, postaxial polydactyly, cognitive impairment, male hypogonadotropic hypogonadism, complex female genitourinary malformations, and renal abnormalities. There is a large clinical and also genetic heterogeneity in BBS. Here, we report a patient with polydactyly, hyperechogenic kidneys increased in size with normal corticomedullary differentiation, anal imperforation, and malformation of genitals with presence of a genital tubercle with ventral urethral meatus associated with two unfused lateral genital swelling and absent urethral folds, in the context of 46, XY karyotype.

Methods: Karyotype and solo exome sequencing were performed to look for a genetic etiology for the features described in our patient.

Results: We identified a homozygous in-frame deletion of exons 4 to 6 in the BBS4 gene (NM-033028 (BBS4-i001): c.[(157-?)_(405 +?)del] p.(Ala53-Trp135del), which is classified as pathogenic variant. This analysis allowed the molecular diagnosis of BBS type 4 in this patient.

Conclusion: Complex genital malformations are only reported in female BBS6 patients yet, and genital abnormalities and anal imperforation are not reported in male BBS4 patients to date. We discuss the possible hypotheses for this phenotype, including the phenotypic overlap between ciliopathies.

Keywords: Bardet-Biedl syndrome; anal imperforation; genital anomalies; sex assignment.

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Conflict of interest statement

The authors have no conflict of interest to declare.

Figures

FIGURE 1
FIGURE 1
Ano‐genital malformations. External genital appearance at the age of day one (a, e), 6 months (b, f), 12 months (c, g), and 19 months (d, h)
FIGURE 2
FIGURE 2
IGV illustration. IGV illustration of the homozygous exon 4 to 6 deletion in the BBS4 gene: this in‐frame deletion theoretically leads to the lack of 83 amino acids in the TPR (Tetratrico Repeat Region) motif of the protein
See this image and copyright information in PMC

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