Sirenomelia and caudal malformations in two families

Gérard, Marion; Layet, Valérie; Costa, Teresa; Roumazeilles, Yves; Chenal, Pierre; Cailliez, Daniel; Gérard, Bénédicte

doi:10.1002/ajmg.a.35408

Cited by 12 publications

(15 citation statements)

References 37 publications

(79 reference statements)

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“…Caudal dysgenesis is hypothesized to arise from a primary deficiency of caudal mesoderm (Duhamel, ; Alles and Sulik, ). This theory is supported by many authors (e.g., Duesterhoeft et al, ; Charlier et al, ; Thottungal et al, ; Gerard et al, ; Seidahmed et al, ; Moosa et al, ; Das et al, ; Lhuaire et al, ; Kaygusuz et al, ). Dias and Walker () suggested that a teratogenic event occurred during gastrulation that interfered with the formation of the notochord, resulting in abnormally developed caudal structures and concomitant neural tube defects.…”

Section: Sirenomelia and Its Overlap With Caudal Dysgenesismentioning

confidence: 69%

“…Other reports concern monozygotic twins in which one of the twins was affected by sirenomelia and the other by imperforated anus (Akbiyik et al, ). Gerard et al () described a mother who had undergone surgery for an imperforate anus and whose first pregnancy was terminated because of bilateral renal agenesis in the fetus. Her second pregnancy was complicated by sirenomelia.…”

Section: Familial Recurrence and Occurrence Of Sirenomeliamentioning

confidence: 99%

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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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Section: Sirenomelia and Its Overlap With Caudal Dysgenesismentioning

confidence: 69%

Section: Familial Recurrence and Occurrence Of Sirenomeliamentioning

confidence: 99%

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

Kim

Morava

Klein

et al. 2017

Birth Defects Research

View full text Add to dashboard Cite

show abstract

“…This allows the conclusion that sirenomelia may exist as a pathologic entity distinct from CD. Interestingly, human cases with minimum or even absent dorsal skeletal and neurological component have also been reported [66], [67].…”

Section: Discussionmentioning

confidence: 99%

“…Yet, human sirenomelia has mainly been considered sporadic since familial cases have only been reported very recently [27]. However, it should be noted that the lack of evidence for a major genetic influence in human mermaid syndrome may rely, at least in part, on the poor documentation of abortions [4], [28].…”

Section: Introductionmentioning

confidence: 99%

Sirenomelia Phenotype in Bmp7;Shh Compound Mutants: A Novel Experimental Model for Studies of Caudal Body Malformations

2012

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Sirenomelia is a severe congenital malformation of the lower body characterized by the fusion of the legs into a single lower limb. This striking external phenotype consistently associates severe visceral abnormalities, most commonly of the kidneys, intestine, and genitalia that generally make the condition lethal. Although the causes of sirenomelia remain unknown, clinical studies have yielded two major hypotheses: i) a primary defect in the generation of caudal mesoderm, ii) a primary vascular defect that leaves the caudal part of the embryo hypoperfused. Interestingly, Sirenomelia has been shown to have a genetic basis in mice, and although it has been considered a sporadic condition in humans, recently some possible familial cases have been reported. Here, we report that the removal of one or both functional alleles of Shh from the Bmp7-null background leads to a sirenomelia phenotype that faithfully replicates the constellation of external and internal malformations, typical of the human condition. These mutants represent an invaluable model in which we have analyzed the pathogenesis of sirenomelia. We show that the signaling defect predominantly impacts the morphogenesis of the hindgut and the development of the caudal end of the dorsal aortas. The deficient formation of ventral midline structures, including the interlimb mesoderm caudal to the umbilicus, leads to the approximation and merging of the hindlimb fields. Our study provides new insights for the understanding of the mechanisms resulting in caudal body malformations, including sirenomelia.

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“…La publication récente de cas familiaux a stimulé la recherche de facteurs génétiques associés à la sirénomélie [8]. Des études expérimentales réalisées chez des rats induisant des mutations perte de fonction des séquences de signalisation du gène « Bone morphogenetic protein » (BMP-7) ou des mutations gain de fonction des séquences de signalisation du gène «retinoic acid » (RA) ont permis d'observer le développement d'un phénotype semblable à celui observé chez l'humain, associant la fusion des membres inférieurs à des malformations pelviennes sévères [9].…”

Section: Discussionunclassified

Sirénomélie (Mermaid Syndrome): description du premier cas Congolais et revue de la littérature

Lubala¹,

Mukuku²,

Mutombo³

2014

Pan Afr Med J

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La sirénomélie est une forme rare de dysgénésie caudale généralement incompatible avec la vie du fait des malformations rénales graves qui y sont associées. En Afrique, elle est associée à des considérations mystico-religieuses et à la sorcellerie et expose la famille à une stigmatisation violente. Son étiologie est encore très controversée. A notre connaissance, il s'agit du premier cas congolais rapporté dans la littérature.

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Sirenomelia and caudal malformations in two families

Cited by 12 publications

References 37 publications

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

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

Sirenomelia Phenotype in Bmp7;Shh Compound Mutants: A Novel Experimental Model for Studies of Caudal Body Malformations

Sirénomélie (Mermaid Syndrome): description du premier cas Congolais et revue de la littérature

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