Prenatal diagnosis of diaphanospondylodysostosis (DSD): a case report

Hofstaetter, C.; Courage, Carolina; Bartholdi, Deborah; Biskup, Saskia; Raio, Luigi

doi:10.1002/ccr3.1368

Cited by 6 publications

(7 citation statements)

References 10 publications

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“…Patients with ISD may present with segmentation and ossification defects of the axial skeleton, resulting in fused or butterfly-shaped vertebrae, ischiosacral hypoplasia, and absent or fused ribs. DSD is an extremely rare and life-threatening disorder, with a known incidence of less than 1 per 1,000,000 pregnancies [17]. Patients with DSD have more severe skeletal malformations than those with ISD, often leading to intrauterine or neonatal death due to respiratory insufficiency.…”

Section: Discussionmentioning

confidence: 99%

Successfully Managed Respiratory Insufficiency in a Patient with a Novel Pathogenic Variant of the BMPER Gene: A Case Report

2022

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Bone morphogenetic protein-binding endothelial cell precursor-derived regulator (BMPER) gene mutation presents a disease spectrum ranging from a mild type of ischiospinal dysostosis (ISD) to a more severe type of diaphanospondylodysostosis (DSD). It is known that BMPER gene mutations are very rare, and their resulting clinical manifestations, including musculoskeletal modifications, appear in a spectrum of various types and severity levels. With the development of genetic diagnosis, case reports of patients with specific mutations in the BMPER gene have been published. The most commonly known clinical features are kidney structural problems, including neuroblastoma and renal cysts. Meanwhile, respiratory failure is a common and fatal symptom for patients with BMPER gene mutation, but it does not appear to have been well evaluated or managed so far. We report a case of a confirmed novel mutation of c.1750delT (p.Cys584fs) in the BMPER gene in a female adolescent patient and highlight the importance of the regular assessment of respiratory failure for successful management of this condition.

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Section: Discussionmentioning

confidence: 99%

Successfully Managed Respiratory Insufficiency in a Patient with a Novel Pathogenic Variant of the BMPER Gene: A Case Report

2022

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“…Diaphanospondylodysostosis and ischiospinal dysostosis are both skeletal dysplasias caused by mutations in the BMPER gene (Funari et al, 2010;Hofstaetter et al, 2018;Kuchinskaya et al, 2016;Legare et al, 2017). Clinical findings partially overlap and there is discussion of them being variants in severity of the same disease process in terms of a clinical continuum with DSD representing the more severe spectrum of the phenotype (Legare et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…Prenatally, the diagnosis of skeletal dysplasia can often be made combined with the most sensitive and specific predictors of the sonographic parameters, namely the degree of femoral shortening, femur length to abdominal circumference ratio, as well as chest circumference to abdominal circumference ratio. Elevated neck translucency on fetal ultrasound was reported repeatedly (Hofstaetter et al, 2018;Prefumo et al, 2003). Early prenatal detection of skeletal dysplasia can be an advantage to preparation on anticipating severity and agreeing on the aggressiveness of measures that are to be taken, particularly assisted ventilation or resuscitation (Krakow, 2015).…”

Section: Diagnosismentioning

confidence: 99%

“…Only few patients who survived beyond infancy are known and the oldest known patient in the literature is 9 years old. Leading causes of death are respiratory insufficiency and Wilms' tumor (Funari et al, 2010;Ben-Neriah et al, 2011;Zong et al, 2015;Kuchinskaya et al, 2016;Hofstaetter et al, 2018;Legare et al, 2017;Salian et al, 2019;Scottoline et al, 2012, Greenbaum et al, 2019. Ischiospinal dysostosis (ISD) is another congenital, polytopic dysostosis associated with mutations in the BMPER gene, but mostly describes a milder phenotype than DSD and may also be associated with nephroblastomatosis (Kuchinskaya et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

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Expansion of the mutational spectrum of BMPER leading to diaphanospondylodysostosis and description of the associated disease process

Braun

Gangfuß

Stöbe

et al. 2021

Molec Gen & Gen Med

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BackgroundDiaphanospondylodysostosis (DSD) is a rare congenital, lethal skeletal disorder caused by recessively inherited mutations in the BMPER gene, which encodes the bone morphogenetic protein‐binding endothelial cell precursor‐derived regulator. The most prominent features of DSD are missing ossification of the axial skeleton, rib abnormalities and thoracic hypoplasia/insufficiency, as well as intralobar nephrogenic rests within the kidneys.MethodsWe report on the case of a 22‐month‐old patient with DSD where trio‐exome sequencing was performed.ResultsGenetic testing revealed a homozygous nonsense variant c.1577G>A (p.Trp526*) in the BMPER gene, leading to a premature stop in protein translation. Both parents are asymptomatic carriers for the BMPER variant, which has not been described in the literature before.ConclusionsOur findings expand the genotypic and phenotypic spectrum of BMPER variants leading to DSD.

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“…To our knowledge, the inner ear phenotype has not been characterised in the mouse, although Bmper is expressed in the murine otic vesicle (Coffinier et al, 2002;Ikeya et al, 2006;Urness et al, 2018). In humans, recessive mutations in BMPER are causative for a family of rare skeletal dysplasias including diaphanospondylodysostosis (DSD), symptoms of which include delayed or absent vertebral ossification, missing ribs and craniofacial and renal anomalies (Ben-Neriah et al, 2011;Funari et al, 2010;Gonzales et al, 2005;Greenbaum et al, 2019;Hofstaetter et al, 2018;Kuchinskaya et al, 2016;Legare et al, 2017;Zong et al, 2015) (OMIM 608022). The most severe cases are perinatal lethal due to respiratory insufficiency; hearing loss was reported in two patients surviving beyond infancy (Kuchinskaya et al, 2016;Scottoline et al, 2012).…”

Section: Expression and Roles In Other Tissues And Comparison With Mammalian Bmper Mutant Phenotypesmentioning

confidence: 99%

Bmper is required for morphogenesis of the anterior and posterior semicircular canal ducts in the developing zebrafish inner ear

Baxendale

et al. 2021

Preprint

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BMP signalling is known to have a conserved function in development of the semicircular canal system of the vertebrate inner ear, but its regulation, target genes and effects on cell behaviour during otic morphogenesis are not fully understood. We have characterised the effects of mutations in the zebrafish gene bmper, which codes for a regulator of BMP signalling with both pro- and anti-BMP roles in different developmental contexts. The inner ears of bmper mutant embryos develop with truncations of the anterior and posterior semicircular canal ducts. To image the developing ear in live embryos, we have exploited a new transgenic line, Tg(smad6b:EGFP), which exhibits strong GFP expression in the otic epithelium. Morphometric analysis indicates defects in the bmper mutant ear from early stages of semicircular canal formation, correlating with a specific reduction in BMP signalling activity and specific loss of dlx5a expression in dorsal otic epithelium. Subsequent changes to cell shape occur at the truncation site and the dorsolateral septum. The bmper mutations that we describe are adult viable; truncation of the anterior and posterior semicircular canal ducts persists into adulthood. Our results argue against a major role for Bmper in specification of the pre-placodal region, induction of the otic placode, or development of the neural crest, processes in which Bmper function has previously been implicated. Instead, we conclude that a key requirement for Bmper function in the zebrafish is to promote BMP signalling during patterning and morphogenesis of the semicircular canal system.

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Prenatal diagnosis of diaphanospondylodysostosis (DSD): a case report

Cited by 6 publications

References 10 publications

Successfully Managed Respiratory Insufficiency in a Patient with a Novel Pathogenic Variant of the BMPER Gene: A Case Report

Successfully Managed Respiratory Insufficiency in a Patient with a Novel Pathogenic Variant of the BMPER Gene: A Case Report

Expansion of the mutational spectrum of BMPER leading to diaphanospondylodysostosis and description of the associated disease process

Bmper is required for morphogenesis of the anterior and posterior semicircular canal ducts in the developing zebrafish inner ear

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