Your Health and Fitness Partner: Androxal & FitHub

We are also excited to expand our scope by including valuable information on Androxal, a potent medication beneficial in various medical conditions. This remarkable drug, derived from the testosterone molecule, has made its mark significantly in the field of endocrinology. Patients and medical professionals can rely on our comprehensive, unbiased, and scientifically grounded content on Androxal for gaining a robust understanding of its uses, side effects, and the latest studies related to it. We understand the necessity of accurate information when it comes to medication. Our newly launched section dedicated to Androxal aims at not only educating the readers about its nuances but also at contributing beneficially to their wellbeing. Stay tuned for insightful articles unraveling the potential of Androxal in medical science.

Sitemap | Policies | Feedback    
 About the Journal
Editorial Board
Journal Subscription
Instructions for Authors
E-mail Alerts
Forthcoming Events
Advertise with Us
Contact Us
 
Article Options
FULL TEXT
PDF
Printer Friendly Version
Search Pubmed for
Search Google Scholar for
Article Statistics
Bookmark and Share
Case Report
 
Ellis Van Creveld syndrome with mesenteroaxial volvulus – expanding the spectrum of endodermal involvement
Keywords :
Susan Jehangir1, Jujju Jacob Kurian1, Gayathri Ulhas Harshe2, Pradeep Joseph Ninan1, Sampath Karl1
Department of Paediatric Surgery1
and Radiodiagnosis2
Christian Medical College Vellore – 632004


Corresponding Author
: Dr. Susan Jehangir
Email: susanjehangir@cmcvellore.ac.in


DOI: http://dx.doi.org/10.7869/tg.289

48uep6bbphidvals|1353
48uep6bbphidcol2|ID
48uep6bbph|2000F98CTab_Articles|Fulltext
Ellis-van Creveld is a rare autosomal recessive disorder with ecto and mesodermal defects.[1] The extent of endodermal involvement in this syndrome is not well established. However there have been reported instances of endodermal involvement in the liver, lung, pancreas and central nervous system.[2-4] The aetiology of gastric volvulus is thought mainly idiopathic, but congenital and acquired associations have also been implicated.[5] Given the strong idiopathic preponderance, and genetic associations; gastric volvulus could occur because of aberrations during endoderm organogenesis. Hedgehog (Hh) signalling plays several important roles during endoderm organogenesis.[6] Hh signalling is one of the critical pathways involved in the development and homeostasis of the mammalian gastrointestinal tract.[7,8] Hh signal is transduced by Smoothened (Smo) forming a complex with EVC/EVC2.[9] Recent study has shown that EVC2 also acts as a positive regulator of the Hh signalling pathway.[10] Furthermore, the genetic and cellular mechanisms involved in the regulation of Hh signalling in the development of mammalian gastrointestinal tract are emerging.[11] This case represents the first instance of gastrointestinal involvement and may thus represent the expanding spectrum of endodermal involvement in EVC.

Case report

A 14-year-old Asian girl with Ellis Van Creveld (EVC) syndrome presented to our hospital for correction of her musculoskeletal deformities. She was the only living child of a healthy nonconsanguineous couple. She was born through normal vaginal delivery at term with birth weight 3.25 kg. Limb anomalies were identified at birth. Another pair of twins with similar musculoskeletal deformities was born to the same couple but died at 4 and 50 days of life.

She achieved normal neuropsycomotor milestones. She attended school till a year ago when the progressive genu valgum causing gait disturbance prevented her from doing the same. She presented to our hospital for treatment of her musculoskeletal anomalies. Physical examination was as follows: height 154 cm and weight 60 kg. Sparce scalp and body hair with hirsuitism. High arched palate with a bifid uvula and conical sharp peg shaped teeth. Bilateral cubitus valgus with broad hands, brachydactyly, polydactyly and syndactyly. Bilateral genu valgum with flat feet. The diagnosis of Ellis Van Creveld syndrome was made based on the above features. Echocardiogram and ultrasound abdomen were normal. She underwent corrective osteotomies for bilateral genu valgum. In the post operative period she developed non bilious vomiting with upper abdominal pain. She was initially treated conservatively, but the episode did not resolve. She had history of similar episodes in the past. Upper gastrointestinal series findings demonstrated a mesenteroaxial volvulus of the stomach (Figure 1). The stomach was decompressed using a nasogastric tube and after gaining an informed consent she underwent a laparoscopic gastropexy. The stomach was found folded below the left lobe of the liver with the distal half congested. The absence of diaphragmatic hernia, splenic anomalies, hiatus hernia and malrotation were confirmed. An anterior gastropexy was performed by placing three interrupted non absorbable sutures along the greater curvature of the stomach. At discharge she was pain free and tolerating solids orally.



Discussion

EVC syndrome is a rare disorder with an incidence of 1 in 60,000 live births.[1] It is an autosomal recessive disorder due to mutations of the EVC and EVC2 genes on chromosome 4p16.[12-13] Till date, more than 41 independent EVC mutations have been described.[14] The features of the syndrome include chondrodystrophy, polydactyly, ectodermal dysplasia, and cardiac defects. However, the clinical presentation is variable, the full spectrum is not necessarily seen in every patient.[15] Rare associated anomalies involving the pulmonary, renal, hepatic, pancreatic, and central nervous systems have been reported previously which underscore the definite endodermal involvement.[2-4] However, the extent of endodermal involvement in this syndrome is not well established.

To the best of our knowledge this is the first reported case of EVC syndrome to include gastric volvulus. Considering other rare anomalies associated with EVC involving the endoderm, gastric volvulus seen in this patient may represent an extension of endodermal involvement. We believe that the accretion of evidence for the endodermal involvement in EVC syndrome may have a mechanistic basis. The aetiology of gastric volvulus has a strong idiopathic predominance.[5] Hedgehog (Hh) signalling plays several specialized roles during endoderm organogenesis.[6] In particular, Hh signalling is also pivotal for the embryonic development and homeostasis of the mammalian gastrointestinal tract.[7,8] A recent study has shown that EVC/ EVC2 acts downstream of Smoothened (Smo) and transduces signal to Gli by antagonizing Sufu.[9] EVC2 also acts as a positive regulator of Hh signalling pathway.10 In addition, Hh signalling has various specialized paracrine functions during embryogenesis of stomach and intestine.[7] Considering the ubiquity of Hh signalling in embryogenesis, the mutated EVC/EVC2 protein in EVC syndrome could lead to wider dysregulation of Hh signalling and its effects may not be restricted entirely to chondrocytes. Therefore, genetic and functional dissection of EVC syndrome with endodermal involvement may provide novel insights into molecular mechanisms to elucidate the aetiology of gastrointestinal diseases with idiopathic preponderance.

In conclusion, gastric volvulus may be a coincidental occurrence or may represent an unusual EVC syndrome association. Hence, this work may serve as a hypothesis generating paper to ascertain the influence of EVC protein mediated regulation of Hh signalling in endodermal involvement, particularly in gastrointestinal diseases with idiopathic preponderance.

References
  1. Muensterer OJ, Berdon W, McManus C, Oestreich A, Lachman RS, Cohen MM, Jr., et al. Ellis-van Creveld syndrome: its history. Pediatr Radiol. 2013;43:1030–6.
  2. Bohm N, Fukuda M, Staudt R, Helwig H. Chondroectodermal dysplasia (Ellis—van Creveld syndrome) with dysplasia of renal medulla and bile ducts. Histopathology. 1978;2:267–81.
  3. Rosemberg S, Carneiro PC, Zerbini MC, Gonzalez CH. Brief clinical report: chondroectodermal dysplasia (Ellis-van Creveld) with anomalies of CNS and urinary tract. Am J Med Genet. 1983;15:291–5.
  4. Brueton LA, Dillon MJ, Winter RM. Ellis-van creveld syndrome, Jeune syndrome, and renal-hepatic-pancreatic dysplasia: separate entities or disease spectrum? J Med Genet. 1990;27:252–5.
  5. Ratan SK, Grover SB. Acute idiopathic mesenteroaxial gastric volvulus in a child. Trop Gastroenterol. 2000;21:133–4.
  6. Zorn AM, Wells JM. Vertebrate endoderm development and organ formation. Annu Rev Cell Dev Biol. 2009;25:221–51.
  7. Kolterud A, Grosse AS, Zacharias WJ, Walton KD, Kretovich KE, Madison BB, et al. Paracrine Hedgehog signaling in stomach and intestine: new roles for hedgehog in gastrointestinal patterning. Gastroenterology. 2009;137:618–28.
  8. Mao J, Kim BM, Rajurkar M, Shivdasani RA, McMahon AP. Hedgehog signaling controls mesenchymal growth in the developing mammalian digestive tract. Development. 2010;137:1721–9.
  9. Yang C, Chen W, Chen Y, Jiang J. Smoothened transduces Hedgehog signal by forming a complex with Evc/Evc2. Cell Res. 2012;22:1593–604.
  10. Blair HJ, Tompson S, Liu YN, Campbell J, MacArthur K, Ponting CP, et al. Evc2 is a positive modulator of Hedgehog signalling that interacts with Evc at the cilia membrane and is also found in the nucleus. BMC Biol. 2011;9:14.
  11. Huang H, Cotton JL, Wang Y, Rajurkar M, Zhu LJ, Lewis BC, et al. Specific requirement of Gli transcription factors in Hedgehogmediated intestinal development. J Biol Chem. 2013;288:17589–96.
  12. Polymeropoulos MH, Ide SE, Wright M, Goodship J, Weissenbach J, Pyeritz RE, et al. The gene for the Ellis-van Creveld syndrome is located on chromosome 4p16. Genomics. 1996;35:1–5.
  13. Ruiz-Perez VL, Ide SE, Strom TM, Lorenz B, Wilson D, Woods K, et al. Mutations in a new gene in Ellis-van Creveld syndrome and Weyers acrodental dysostosis. Nat Genet. 2000;24:283–6.
  14. Ruiz-Perez VL, Goodship JA. Ellis-van Creveld syndrome and Weyers acrodental dysostosis are caused by cilia-mediated diminished response to hedgehog ligands. Am J Med Genet C Semin Med Genet. 2009;151C:341–51.
  15. Scurlock D, Ostler D, Nguyen A, Wahed A. Ellis-van Creveld syndrome and dyserythropoiesis. Arch Pathol Lab Med. 2005;129:680–2.