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

Sirenomelia is a very rare limb anomaly in which the normally paired lower limbs are replaced by a single midline limb. This study describes the prevalence, associated malformations, and maternal characteristics among cases with sirenomelia. Data originated from 19 birth defect surveillance system members of the International Clearinghouse for Birth Defects Surveillance and Research, and were reported according to a single pre-established protocol. Cases were clinically evaluated locally and reviewed centrally. A total of 249 cases with sirenomelia were identified among 25,290,172 births, for a prevalence of 0.98 per 100,000, with higher prevalence in the Mexican registry. An increase of sirenomelia prevalence with maternal age less than 20 years was statistically significant. The proportion of twinning was 9%, higher than the 1% expected. Sex was ambiguous in 47% of cases, and no different from expectation in the rest. The proportion of cases born alive, premature, and weighting less than 2,500 g were 47%, 71.2%, and 88.2%, respectively. Half of the cases with sirenomelia also presented with genital, large bowel, and urinary defects. About 10-15% of the cases had lower spinal column defects, single or anomalous umbilical artery, upper limb, cardiac, and central nervous system defects. There was a greater than expected association of sirenomelia with other very rare defects such as bladder exstrophy, cyclopia/holoprosencephaly, and acardia-acephalus. The application of the new biological network analysis approach, including molecular results, to these associated very rare diseases is suggested for future studies.

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“…Sirenomelia/CRS and situs inversus in the same case were reported by Langer et al [1999] and Rougemont et al [2008].…”

Section: Introductionsupporting

confidence: 77%

Sirenomelia: An epidemiologic study in a large dataset from the International Clearinghouse of Birth Defects Surveillance and Research, and literature review

Orioli¹,

Amar²,

Arteaga‐Vázquez

et al. 2011

American J of Med Genetics Pt C

139

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“…It is beyond the scope of this review to include all these case studies. However, some papers are noteworthy because they report associated anomalies normally discordant in “classic” or “isolated” sirenomelia, they included a nephroblastoma (Kimura et al, ), neuroblastoma, and gallbladder agenesis (Drossou‐Agakiou et al, ), double inferior vena cava (Goodlow et al, ), pentalogy of Cantrell (Egan et al, ), acardia (Zanforlin Filho et al, ), dextrocardia (Cavaliere et al, ), situs inversus totalis (Langer et al, ; Sivridis et al, ; Rougemont et al, ), limb‐body wall complex (Tang et al, ; Martínez‐Frías et al, ), and amniotic band disruptions sequence (Managoli et al, ).…”

Section: Associated “Non Classical” Anomalies In Sirenomeliamentioning

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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“…The exact etiology of this syndrome is unclear. A vascular steal phenomenon causing relative ischemia below a persistent vitelline artery, genetic factors, teratogens and maternal diabetes have been hypothesized to play a role in its pathogenesis [4,5]. In our present case, the antenatal history was uneventful and the mother was non-diabetic.…”

Section: Discussionmentioning

confidence: 56%

Caudal regression syndrome with vestigial tail and esophageal duplication cyst

Mandal

Hembram

2015

J Pediatr Neurol

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Caudal dysgenesis constitutes a heterogeneous spectrum of congenital caudal anomalies, including varying degrees of developmental defects of the vertebral column, as well as anorectal and genitourinary anomalies. Herein, we are reporting a case of caudal regression syndrome with imperforate anus, bilateral renal hypoplasia, vestigial tail and esophageal duplication cyst in a baby of non-diabetic mother,

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

Cited by 18 publications

References 38 publications

Sirenomelia: An epidemiologic study in a large dataset from the International Clearinghouse of Birth Defects Surveillance and Research, and literature review

Sirenomelia: An epidemiologic study in a large dataset from the International Clearinghouse of Birth Defects Surveillance and Research, and literature review

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

Caudal regression syndrome with vestigial tail and esophageal duplication cyst

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