Meckel-Gruber syndrome: A rare and lethal anomaly with review of literature

Parelkar, Sandesh; Kapadnis, Satish P.; Sanghvi, Beejal; Joshi, Prashant; Mundada, Dinesh; Oak, Sanjay

doi:10.4103/1817-1745.117855

Cited by 33 publications

(23 citation statements)

References 11 publications

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“…25 We observed 2-and 3-fold higher cystogenic potentials in cultured Pkd1 m1Bei/+ and Pkd1 m1Bei/m1Bei kidneys, respectively, relative to wt ( Figure 7B). 40 The clinical relevance of THM1 is underscored by the finding that THM1 contributes the most pathogenic alleles in patients with infantile and pediatric ciliopathies. 24 Further, Thm1 ablation during late embryogenesis results in cystic kidney disease in adulthood, showing that THM1 loss can cause both pediatric and adult forms of the cystic kidney disease spectrum.…”

Section: Small Molecule Hh Inhibitors Do Notmentioning

confidence: 99%

Downregulating Hedgehog Signaling Reduces Renal Cystogenic Potential of Mouse Models

Tran

Talbott

Turbé-Doan

et al. 2014

Journal of the American Society of Nephrology

110

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Renal cystic diseases are a leading cause of renal failure. Mutations associated with renal cystic diseases reside in genes encoding proteins that localize to primary cilia. These cystoproteins can disrupt ciliary structure or cilia-mediated signaling, although molecular mechanisms connecting cilia function to renal cystogenesis remain unclear. The ciliary gene, Thm1(Ttc21b), negatively regulates Hedgehog signaling and is most commonly mutated in ciliopathies. We report that loss of murine Thm1 causes cystic kidney disease, with persistent proliferation of renal cells, elevated cAMP levels, and enhanced expression of Hedgehog signaling genes. Notably, the cAMP-mediated cystogenic potential of Thm1-null kidney explants was reduced by genetically deleting Gli2, a major transcriptional activator of the Hedgehog pathway, or by culturing with small molecule Hedgehog inhibitors. These Hedgehog inhibitors acted independently of protein kinase A and Wnt inhibitors. Furthermore, simultaneous deletion of Gli2 attenuated the renal cystic disease associated with deletion of Thm1. Finally, transcripts of Hedgehog target genes increased in cystic kidneys of two other orthologous mouse mutants, jck and Pkd1, and Hedgehog inhibitors reduced cystogenesis in jck and Pkd1 cultured kidneys. Thus, enhanced Hedgehog activity may have a general role in renal cystogenesis and thereby present a novel therapeutic target.

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Section: Small Molecule Hh Inhibitors Do Notmentioning

confidence: 99%

Downregulating Hedgehog Signaling Reduces Renal Cystogenic Potential of Mouse Models

Tran

Talbott

Turbé-Doan

et al. 2014

Journal of the American Society of Nephrology

110

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“…9 Los criterios mínimos para establecer el diagnóstico clínico de MGS son la presencia de al menos dos de las tres manifestaciones principales, es decir, displasia renal quística bilateral, meningoencefalocele occipital y polidactilia. 2,3,8 En este caso, la paciente contó con los componentes de la triada clásica, además de otras características que apoyan el diagnóstico como oligohidramnios, microcefalia, cardiopatía congénita y alteraciones del sistema nervioso central identificadas en los estudios de neuroimagen. 13 Los diagnósticos diferenciales de MGS incluyen al síndrome de Bardet-Biedl, al síndrome de Smith-Lemli-Opitz y a la trisomía 13.…”

Section: Discussionunclassified

“…[1][2][3] Fue descrito por primera vez en 1822. Es un trastorno autosómico recesivo letal caracterizado por una triada de manifestaciones: displasia renal quística bilateral, meningoencefalocele occipital y polidactilia postaxial.…”

Section: Introductionunclassified

“…Es un trastorno autosómico recesivo letal caracterizado por una triada de manifestaciones: displasia renal quística bilateral, meningoencefalocele occipital y polidactilia postaxial. [1][2][3][4][5] Se puede acompañar de una amplia variedad de malformaciones entre las que destacan la fisura palatina descrita por Meckel en 1822 y la fibrosis hepática descrita por Gruber en 1934. 5,6 La prevalencia estimada a nivel mundial oscila entre 1/1,300 hasta 1/140,000.…”

Section: Introductionunclassified

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Síndrome de Meckel-Gruber en un lactante menor con sobrevida prolongada. Reporte de Caso

et al. 2018

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El síndrome de Meckel-Gruber es una ciliopatía debida a la disfunción del cilio celular; un trastorno autosómico recesivo letal que se caracteriza por una triada clásica de manifestaciones: displasia renal quística bilateral, meningoencefalocele occipital y polidactilia postaxial. Se presenta el caso de una lactante que al nacer presentó la triada del síndrome de Meckel-Gruber y otras alteraciones, entre las que destacó la aplasia bilateral del nervio óptico. A las 72 horas de vida fue sometida a exéresis de meningoencefalocele occipital con evolución satisfactoria, continuó con tratamiento por infecciones urinarias a repetición debido a displasia quística renal, también padeció infecciones respiratorias y falleció a los 11 meses de vida. Pese a la alta mortalidad del síndrome de Meckel-Gruber en algunos casos, poco frecuentes como éste, la sobrevida de extiende, por lo que es necesario un tratamiento multidisciplinario para tratar las complicaciones.

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“…1 Multitude of anomalies that may be associated with MGS include cleft lip and palate, ambiguous genitalia, cardiac septal defects, gastrointestinal anomalies like omphalocele, and CNS abnormalities like agenesis of corpus callosum, Dandy-Walker cyst, and Arnold-Chiari malformations. 7 The role of early prenatal diagnosis lies in the fact that the condition being 100% fatal needs termination of pregnancy. However, there is one report of survival up to 28 months.…”

Section: Discussionmentioning

confidence: 99%

The Case of Recurrent Lethal Fetal Syndrome: Meckel–Gruber Syndrome

Aggarwal¹,

Ahmad²,

Radhakrishnan³

et al. 2017

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Meckel-Gruber syndrome (MGS), a rare lethal syndrome, is characterized phenotypically by polycystic kidneys, occipital encephalocele, and postaxial polydactyly. This entity with 100% fatality has autosomal recessive transmission with multiple gene loci. Mutation analysis is the confirmatory test to label a case as MGS. However, two of the three above-mentioned anomalies are sufficient to arrive at a working diagnosis of MGS. We report a case of MGS in a family with a history suggestive of multiple affected fetuses previously. Early diagnosis at 13 weeks gestation was made on antenatal ultrasound examination and the findings were confirmed on postabortal autopsy.

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Meckel-Gruber syndrome: A rare and lethal anomaly with review of literature

Cited by 33 publications

References 11 publications

Downregulating Hedgehog Signaling Reduces Renal Cystogenic Potential of Mouse Models

Downregulating Hedgehog Signaling Reduces Renal Cystogenic Potential of Mouse Models

Síndrome de Meckel-Gruber en un lactante menor con sobrevida prolongada. Reporte de Caso

The Case of Recurrent Lethal Fetal Syndrome: Meckel–Gruber Syndrome

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