Prenatal and Postnatal Diagnostics of a Child with Bardet-Biedl Syndrome: Case Study

Abstract

Bardet Biedl Syndrome (BBS) is a rare, genetically determined syndrome which can result from a mutation in one of 19 known genes (often called BBS complex), which play a vital role in building structures and cell functions of cilia. Phenotypic symptoms of the syndrome usually progress in the first decade of life, however, they are characterized by a high diversity which makes their diagnosis difficult, especially in the early stage of life. The diagnosis is most frequently based on clinical symptoms and established in late childhood or adult life. BBS is a disorder of the non-motile cilia, which play the role of antennae receiving and transmitting sensory signals to photoreceptors of the retina, hearing cells or olfactory cells. Clinical symptoms of the disorders affecting these structures are: retinal pigmentary degeneration, polydactyly, learning difficulties, and formation of kidney, liver and pancreas cysts. The inheritance mode of BBS is in 80% autosomal recessive, which is connected with both parents carrying a mutated allele, and usually only giving birth to a symptomatic child defines a family as being at genetic risk, whith 25% risk of having another child with the disease and 50% of having offspring that are asymptomatic carriers For families with an identified mutation there exists a possibility of conducting prenatal or preimplementation genetic diagnosis in subsequent pregnancies The article presents a case of a patient in whom prenatal ultrasonography and subsequent clinical trials in post-natal period resulted in a Bardet-Biedl syndrome diagnosis, which was later confirmed through molecular tests.

Screening for mutation hotspots in Bardet–Biedl syndrome patients from India

“…The study revealed that BBS10 gene mutations were more common when compared to the other genes as has been reported earlier 18 . However, we were unable to replicate the results of other genes, probably due to genetic heterogeneity of the disease.…”

“…A detailed clinical history of other systemic features has also been recommended 17 . There are reports on diagnosis of BBS through prenatal ultrasonography which was subsequently confirmed postnatally through clinical evaluation and molecular confirmation 18 .…”

Fetal ciliopathies: a retrospective observational single-center study

“…Hydronephrosis was the leading renal abnormality and present in all our MKKS/BBS cases with either normal or enhanced amniotic fluid in 83% of all cases. Compared to other multisystem ciliopathies, average GA at diagnosis in fetuses with MKKS/BBS was significantly higher in our study cohort, however, detection of ultrasound abnormalities in fetuses with BBS as early as at 15 weeks has been described [19]. All our MKKS/BBS fetuses were female, but MKKS/BBS in males is possible and can be accompanied by genital malformations or hypogonadism.…”

“…MKKS is usually diagnosed on the basis of the typical diagnostic triad Fig. 2 Pre-and postnatal (postmortem) imaging in a fetus with Jeune syndrome: prenatal ultrasound showed a micromelia with a curved femur as well as b kidneys with missing corticomedullary differentiation at 21 + 3 weeks; c-e postnatal (post-mortem) radiography of the stillborn (TOP at 22 + 3 weeks): note the micromelia with the curved long bones as well as short ribs; e shows the typical "trident" appearance of the acetabular roof (white arrows) of hydrometrocolpos, postaxial polydactyly and congenital cardiac disease [19][20][21], which, in our cohort, were present in 83%, 67%, and 50%, respectively. Hydronephrosis was the leading renal abnormality and present in all our MKKS/BBS cases with either normal or enhanced amniotic fluid in 83% of all cases.…”

Computational and Structural Analysis to Assess the Pathogenicity of Bardet-Biedl Syndrome Related Missense Variants Identified in Bardet-Biedl Syndrome 10 Gene (BBS10)

“…10,16 Nevertheless, missense mutations could also be deleterious; however, the impact of identified missense mutations is rarely studied. 17,18 Consequently, it is crucial to develop in silico approaches to identify the significant functional mutations that might aid in the early detection and clinical management of BBS.…”