Prenatal Diagnosis of Sirenomelia with Bilateral Hydrocephalus: Report of a Previously Undocumented form of VACTERL-H Association

Onyeije, Chukwuma I.; Sherer, David M.; Handwerker, Sara M.; Shah, Leena

doi:10.1055/s-2007-993925

Cited by 21 publications

(13 citation statements)

References 12 publications

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“…In the first fetus we describe here, sirenomelia was associated with a hydrocephalus due to an atresia of the aqueduct of Sylvius. Sirenomelia has been reported in a few instances in association with hydrocephalus [Stocker and Heifetz, 1987;Onyeije et al, 1998], and a phenotypic overlap has been observed between sirenomelia and the VACTERL-H association (OMIM 276950; VACTERL association with hydrocephalus) [Onyeije et al, 1998], an association linked to a PTEN mutation [Reardon et al, 2001]. …”

Section: Discussionmentioning

confidence: 99%

Caudal dysgenesis, sirenomelia, and situs inversus totalis: A primitive defect in blastogenesis

Rougemont

Soglio

Désilets

et al. 2008

American J of Med Genetics Pt A

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Caudal dysgenesis (CD) constitutes a heterogeneous spectrum of congenital caudal anomalies, including varying degrees of agenesis of the vertebral column, as well as anorectal and genitourinary anomalies. Sirenomelia, characterized by a fusion of the lower limbs, could represent the most severe end of this spectrum. The two main debated pathogenic hypotheses are an aberrant vascular supply versus a primary axial mesoderm defect. We present the autopsy findings of two fetuses of non-diabetic mothers, with normal karyotype. Both fetuses presented situs inversus associated with a CD, in one case consisting of sirenomelia, establishing a very rare association profile that might be random. This association also suggests the occurrence of a common pathogenic mechanism, in accordance to recent genetic data, such as displayed in the Kif3A murine mutation phenotype. Some cases of sirenomelia and CD could represent developmental field defects of blastogenesis involving the caudal mesoderm, rather than being related to vascular insufficiency.

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Section: Discussionmentioning

confidence: 99%

Caudal dysgenesis, sirenomelia, and situs inversus totalis: A primitive defect in blastogenesis

Rougemont

Soglio

Désilets

et al. 2008

American J of Med Genetics Pt A

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“…The prevalence of VACTERL(H) phenotypes in Fanconi anemia patients ranges from 5% to as much as 44%, depending on the mutated gene (Alter et al, ; McCauley et al, ; Savage et al, ; Mikat et al, ). Multiple reports exist that describe VACTERL(‐H) associations in combination with sirenomelia (Onyeije et al, ; Charlier et al, ; Castori et al, ; Moosa et al, ; Lhuaire et al, ) and several more in which the concomitant conditions were not recognized as being part of the VACTERL(H) association (see previously). Intriguingly, disturbances in the Shh signaling pathway in mice causes a VACTERL‐like phenotope (Kim et al, ), in addition to its role in both sirenomelia and HPE (see previously).…”

Section: Sirenomelia and Its Overlap With Vater/vacterl(h) Associationsmentioning

confidence: 99%

“…Sirenomelia is still the subject of debate, due to its ongoing controversies regarding its etiopathogenesis. Sirenomelia shows a heterogeneous phenotypic variability and overlap with caudal regression syndrome/sacro‐coccygeal dysgenesis (Duhamel, ; Stocker and Heifetz, ; Adra et al, ), small pelvic outlet syndrome (Currarino and Weinberg, ), VATER/VACTERL (Young et al, ; Schüler and Salzano, ; Jain et al, ; Moosa et al, ), and VACTERL‐H associations (Onyeije et al, ). There have been several attempts to classify these receptacles of caudal malformations, unfortunately without satisfying results.…”

Section: Introductionmentioning

confidence: 99%

Sirenomelia: A Multi‐systemic Polytopic Field Defect with Ongoing Controversies

Kim

Morava

Klein

et al. 2017

Birth Defects Research

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The most impressive phenotypic appearance of sirenomelia is the presence of a 1808-rotated, axially positioned, single lower limb. Associated gastrointestinal and genitourinary anomalies are almost always present. This rare anomaly is still the subject of ongoing controversies concerning its nosology, pathogenesis, and possible genetic etiology. Sirenomelia can be part of a syndromic continuum, overlapping with other complex conditions including caudal dysgenesis and VATER/VACTERL/VACTERL-H associations, which could all be part of a heterogeneous spectrum, and originate from an early defect in blastogenesis. It is imaginable that different "primary field defects," whether or not genetically based, induce a spectrum of caudal malformations. In the current study, we review the contemporary hypotheses and conceptual approaches regarding the etiology and pathogenesis of sirenomelia, especially in the context of concomitant conditions. To expand on the latter, we included the external and internal dysmorphology of one third trimester sirenomelic fetus from our anatomical museum collection, in which multiple concomitant but discordant anomalies were observed compared with classic sirenomelia, and was diagnosed as VACTERL-H association with sirenomelia. Key words: blastogenesis; caudal dysgenesis; mermaid syndrome; anatomical museum; sirenomelia; teratology; VACTERL; VACTERL-H; VATER IntroductionThe most obvious phenotypic characteristic in sirenomelia (also called: symmelia or mermaid syndrome) is the single axially positioned lower limb. However, sirenomelia can be seen as a (lethal) multi-system condition based on a polytopic field defect with a wide phenotypical variability and frequently observed co-occurring with musculoskeletal, central nervous system, cardiopulmonary and other visceral anomalies, in addition to the almost always present gastrointestinal and genitourinary anomalies (reviewed by Gabriele and Gianpaolo, 2013). Sirenomelia is still the subject of debate, due to its ongoing controversies regarding its etiopathogenesis. Sirenomelia shows a heterogeneous phenotypic variability and overlap with caudal regression syndrome/sacro-coccygeal dysgenesis (Duhamel, 1961;Stocker and Heifetz, 1987;Adra et al., 1994), small pelvic outlet syndrome (Currarino and Weinberg, 1991), VATER/ VACTERL (Young et al., 1986;Sch€ uler and Salzano, 1994;Jain et al., 2002;Moosa et al., 2012), and VACTERL-H associations (Onyeije et al., 1998). There have been several attempts to classify these receptacles of caudal malformations, unfortunately without satisfying results. Clearly, diagnostic overlap exists between these conditions and the interpretation of their etiopathogenetic origin.The purpose of this study is to give an overview of multiple facets of this dysmorphological puzzle and review what is known about the co-occurrence of sirenomelia and other birth defects, in particular those assigned to the VACTERL(-H) spectrum. The existing literature on these conditions is supplemented by one additional case of sirenomelia with ...

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“…Its incidence is estimated to be about 1.5 to 4.2 per 100 000 births, and is higher in monozygotic twins than in dizygotic twins or singletons. Males are three times more often affected than females (Stocker and Heifetz 1987;Onyeije et al 1998). The sequence of sirenomelia is characterized by a variable nature of lower limb abnormalities associated with severe gastrointestinal and urogenital malformations (Kampmeier 1927;Stocker and Heifetz 1987;Kjaer et al 2003;Drossou-Agakidou et al 2004;Duesterhoeft et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Sirenomelia with a de novo balanced translocation 46,X,t(X;16)(p11.23;p12.3)

Kurosawa

Tanoshima-Takei

Yamamoto

et al. 2012

Congenital Anomalies

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We report a female fetus with sirenomelia with 46,X,t(X;16)(p11.23;p12.3) de novo. Fluorescence in situ hybridization (FISH) with bacterial artificial chromosomes were employed for narrowing down the breakpoint regions. On chromosome 16, the breakpoint was mapped in the region of RP11-453F10 (19 920 640-20 118 153 bp from 16pter). On chromosome X, the breakpoint was mapped in the region of RP11-794A15 (47 333 744-47 524 066 bp from Xpter). This is the first case report of sirenomelia associated with translocations. The abnormal phenotype, associated with a balanced translocation, was caused by deletion or breakage of dosage-sensitive genes of the breakpoint, disruption of an imprinted gene, or uniparental disomy. Although the parental origin of normal 16 and der(16) remained undetermined, this case will provide insight into the pathogenetic mechanism of sirenomelia.

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Prenatal Diagnosis of Sirenomelia with Bilateral Hydrocephalus: Report of a Previously Undocumented form of VACTERL-H Association

Cited by 21 publications

References 12 publications

Caudal dysgenesis, sirenomelia, and situs inversus totalis: A primitive defect in blastogenesis

Caudal dysgenesis, sirenomelia, and situs inversus totalis: A primitive defect in blastogenesis

Sirenomelia: A Multi‐systemic Polytopic Field Defect with Ongoing Controversies

Sirenomelia with a de novo balanced translocation 46,X,t(X;16)(p11.23;p12.3)

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