Introduction Hennekam syndrome is an autosomal recessive disease with lymphangiectasia, severe peripheral lymphedema, abnormalities of the face, cramps, mild growth and mental retardation. The aim of the study to describe the clinical characteristics of Hennekam syndrome. Search strategy. The databases of Scopus, Web of Science, and PubMed were used to conduct a comprehensive literature search. Complete publications that had been released in peer-reviewed journals up through May 2023 were chosen. Search parameters included the terms "Hennekam syndrome" and "Lymphedema-Lymphangiectasia-Mental Retardation Syndrome." Thus, 83 publications were discovered, from which 53 articles were chosen. Results: The literature describes more than 50 cases Hennekam syndrome. Lymphedema, resulting hypoplasia lymphatic system usually appears at birth and in early infancy, in the form of swelling of limbs, genitals, face and eyes. Intestinal lymphangiectasia can lead to protein-losing enteropathy, mild growth retardation, peripheral edema, and ascites. At biochemical study determined hypogammaglobulinemia, hypoalbuminemia, lymphopenia and increased alpha-1 antitrypsin. In this article, a review of the literature and descriptions of each reported case of Hennekam syndrome were made.
Assylzhan M. Messova1, https://orcid.org/0000-0001-5373-0523 Kuat D. Akimzhanov1, https://orcid.org/0000-0003-1886-0538 Oxana Yurkovskaya1, https://orcid.org/0000-0002-6251-5574 Yerbol M. Smail1, https://orcid.org/0000-0003-3881-3747 Samatbek T. Abdrakhmanov1, https://orcid.org/0000-0002-4270-3498 Altynai K. Adilbaeva2, Anar S. Karazhanova3 1 Semey Medical University, Semey, Republic of Kazakhstan; 2 Viamedis, Pavlodar, Republic of Kazakhstan; 3 Astana Medical University, Astana, Republic of Kazakhstan.
1. Aagenaes Y. Hereditary Cholestasis with Lymphoedema (Aagenaes Syndrome, Cholestasis-Lymphoedema Syndrome): New Cases and Follow-up from Infancy to Adult Age // Scandinavian Journal of Gastroenterology. 1998. 33(4). 335-345. 2. Al-Gazali L. I., Hertecant J., Ahmed R., Khan N. A., Padmanabhan R. Further delineation of Hennekam syndrome // Clin. Dysmorph. 2003. 12.p. 227-232. 3. Alders M., Al-Gazali L., Cordeiro I., Dallapiccola B., Garavelli L., Tuysuz B., Salehi F., Haagmans M. A., Mook O.R., Majoie C.B., Mannens M.M., Hennekam R.C. Hennekam syndrome can be caused by FAT4 mutations and be allelic to Van Maldergem syndrome // Hum. Genet. 2014. 133. p.1161-1167. 4. Alders M., Hogan B.M., Gjini E., Salehi F., Al-Gazali L., et al. Mutations in CCBE1 cause generalized lymph vessel dysplasia in humans // Nature Genet. 2009. 41. p. 1272-1274. 5. Al Sinani S., Yusria Al. R., Hamed A. Octreotide in Hennekam syndrome-associated intestinal lymphangiectasia // World J Gastroenterol. 2012. 18(43). p. 6333-6337. 6. Angle B., Hersh J.H. Expansion of the Phenotype in Hennekam Syndrome: A Case With New Manifestations // American Journal of Medical Genetics.1997. 71. p. 211–214. 7. Bellini C., Mazzella M., Arioni C., Campisi C., Taddei, G., Toma P., Boccardo F., Hennekam R. C., Serra G. Hennekam syndrome presenting as nonimmune hydrops fetalis, congenital chylothorax, and congenital pulmonary lymphangiectasia // Am. J. Med. Genet. 2003. 120A. p. 92-96. 8. Bektas H., Bulbul Y., Ozsu S., Ozlu T. A Rare Cause of Chylothorax: Hennekam Syndrome // Turk Thorac J. 2015. 16.p. 33-35. 9. Boone P.M., Paterson S., Mohajeri K., Zhu W,. Genetti C.A., Tai D.J.C.,et al. Biallelic mutation of FBXL7 suggests a novel form of Hennekam syndrome // Am J Med Genet A. 2020 Jan;182(1):189-194. 10. Connell F., Kalidas, K., Ostergaard P., Brice G., Homfray T., Roberts L., et al. Lymphoedema Consortium. Linkage and sequence analysis indicate that CCBE1 is mutated in recessively inherited generalised lymphatic dysplasia // Hum. Genet. 2010. 127. p. 231-241. 11. Cormier-Daire V., Lyonnet S., Lehnert A., Martin D., Salomon R., Patey N., Broyer M., Ricour C., Munnich A. Craniosynostosis and kidney malformation in a case of Hennekam syndrome // Am. J. Med. Genet. 1995. 57.p. 66-68. 12. Crawford J., Bower N.I., Hogan B.M., Taft R.J., Gabbett M.T,. McGaughran J., Simons C. Expanding the genotypic spectrum of CCBE1 mutations in Hennekam syndrome // Am J Med Genet A. 2016 Oct;170(10):2694-7. 13. Deng X.L., Yin F., Zhang G.Y., Duan Y.D. A complicated case study: Hennekam syndrome // Zhongguo Dang Dai Er Ke Za Zhi. 2015 Jan;17(1):77-80. Chinese. 14. Döffinger R., Smahi A., Bessia C., Geissmann F., Feinberg J., Durandy A. X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-κB signalling // Nature genetics. 2001. 27. 277-285. 15. Elmansour I., Chiheb S., Benchikhi H. Hennekam syndrome: a rare cause of primary lymphedema // Dermatology Online Journal. 20 (8). p. 16. 16. Erkan T., Kutlu T., Cullu F., Celik M., Demir T., Tiiysiiz B., Tiimay C.T. Syndrome de Hennekam // Arch Pediatr. 1998. 5. p. 1344-6. 17. Fattorusso A., Pieri E.S., Dell'Isola G.B., Prontera P., Mencaroni E., Stangoni G., Esposito S. Intestinal lymphangiectasia in a 3-month-old girl: A case report of Hennekam syndrome caused by CCBE1 mutation // Medicine (Baltimore). 2020 Jul 2;99(27):e20995. 18. Forzano F., Faravelli F., Loy A., Di Rocco M. Severe lymphedema, intestinal lymphangiectasia, seizures and mild mental retardation: further case of Hennekam syndrome with a severe phenotype // Am. J. Med. Genet. 2002. 111. p. 68-70. 19. Frosk P., Chodirker B., Simard L., El-Matary W., Hanlon-Dearman A., et al. A novel CCBE1 mutation leading to a mild form of hennekam syndrome: case report and review of the literature // BMC Medical Genetics. 2015.16. p. 28. 20. Gabrielli O., Catassi C., Carlucci A., Coppa G. V., Giorgi P. Intestinal lymphangiectasia, lymphedema, mental retardation, and typical face: confirmation of the Hennekam syndrome // Am. J. Med. Genet. 1991. 40. p. 244-247. 21. Gelb B.D., Tartaglia M. Noonan syndrome and related disorders: dysregulated RAS-mitogen activated protein kinase signal transduction // Hum Mol Genet. 2006. 15. 220-226. 22. Granzow JW, Soderberg JM, Kaji AH, Dauphine C. Review of current surgical treatments for lymphedema // Ann Surg Oncol. 2014.21.1195–1201. 23. Hennekam R.C.M., Geerdink R.A., Hamel B.C.J., Hennekam F.A.M., Kraus P., Rammeloo J.A., Tillemans A.A.W. Autosomal recessive intestinal lymphangiectasia and lymphedema, with facial anomalies and mental retardation // Am. J. Med. Genet. 1989. 34. p. 593-600. 24. Hourihane O'B., Bennett C.P., Chaudhuri R., Robb S.A., Martin N.D. A Sibship with a Neuronal Migration Defect, Cerebellar Hypoplasia and Congenital Lymphedema // Neuropediatrics. 1993. 24. 43-46. 25. Huppke P.., Christen H.J., Sattler B., Hanefeld F. Two brothers with Hennikam syndrome and cerebral abnormalities // Clinical dysmorphology. 2000. 9. p. 21-24. 26. Ivanovski I., Akbaroghli S., Pollazzon M., Gelmini C., Caraffi S.G., et al. Hennekam RC. Van Maldergem syndrome and Hennekam syndrome: Further delineation of allelic phenotypes // Am J Med Genet A. 2018 May;176(5):1166-1174. 27. Jackson C.C., Best L., Lorenzo L., Casanova J.L., Wacker J., et al. Multiplex Kindred with Hennekam Syndrome due to Homozygosity for a CCBE1 Mutation that does not Prevent Protein Expression // J Clin Immunol. 2016 Jan;36(1):19-27. 28. Zhang N, Shen WB, Cai HC, Yan XM, Liu SL,et al. [Hennekam syndrome: a case report and review of literature]. Zhonghua Nei Ke Za Zhi. 2013 Mar;52(3):192-6. Chinese. 29. Lakshminarayana G., Mathe A.W., Rajesh R., Kurien G., Unni V.N. Hennekam lymphangiectasia syndrome // Indian Journal of Nephrology. 2011. Vol 21. Issue 4. p. 273-275. 30. Lee Y.G., Kim S.C, Park S.B., Kim M.J.. Hennekam Syndrome: A Case Report // Ann Rehabil Med. 2018 Feb;42(1):184-188. 31. Mandula P.P., Malik R., Khanna G. Protein Losing Enteropathy in Hennekam Syndrome. // Indian J Pediatr. 2018 Jul;85(7):587-588. 32. Menon J., Venkatesh V., Thirunavukkarasu B., Lal S.B. Hennekam syndrome: an uncommon cause of chylous ascites and intestinal lymphangiectasia in the tropics // BMJ Case Rep. 2019 Jul 19;12(7).e229419. 33. Melber D.J., Andreasen T.S., Mao R., Tvrdik T., Miller C.E. et al. Novel mutation in CCBE 1 as a cause of recurrent hydrops fetalis from Hennekam lymphangiectasia-lymphedema syndrome-1 // Clin Case Rep. 2018 Oct 24;6(12).2358-2363. 34. Messova A.M., Lindley K.J., Kӧglmeier J. Growth Failure, Micronutrient Deficiency and Autoimmunity-A New Phenotype of Hennekam Syndrome // J Dig Dis Hepatol 2022. 6. 183. 35. Musumeci ML, Nasca MR, De Pasquale R, Schwartz RA, Micali G. Cutaneous manifestations and massive genital involvement in Hennekam syndrome // Pediatr Dermatol. 2006 May-Jun;23(3):239-42. 36. Nisli K., Oner N., Kayserili H. et al. A case of Hennekam syndrome presenting with massive pericardial effusion // Turk Kardiyol Dern Ars. 2008. 36. p. 325–328. 37. Pap Z., Biro T., Szabo L., Papp Z. Syndrome of Lymphoedema and Distichiasis // Hum. Genet. 1980. 53.309-310. 38. Philip J. Dahlberg, William Borer, Kermit L. Newcomer, Wilfrido R. Yutuc Autosomal or X-linked Recessive Syndrome of Congenital Lymphedema, Hypoparathyroidism, Nephropathy, Prolapsing Mitral Valve, and Brachytelephalangy // American Journal of Medical Genetics. 1983. 16. p.99-104. 39. Rao B.S., Vani M.S., Kanth B.S. Hennekam lymphangiectasia syndrome International Journal of Research in Medical Sciences // Int J Res Med Sci. 2015. 3(2). p.516-519. 40. Ren Y., Liu Y., Lyu Y., Gao M., Wang D., et al. Variant analysis of CCBE1 gene in a case of Hennekam lymphangiectasia-lymphedema syndrome type 1. // Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2020 Jun 10;37(6):669-672. Chinese. 41. Rockson S.G., de los Santos M., Szuba A. Lymphoscintigraphic manifestations of Hennekam syndrome--a case report // Angiology. 1999. 254p. 42. Sanke S., Garg T., Manickavasagam S., Chander R.. Hennekam lymphangiectasia syndrome: A rare case of primary lymphedema // Indian J Dermatol Venereol Leprol. 2021 Mar-Apr. 87(2):240-244. 43. Scarcella A., De Lucia A., Pasquariello M.B., Gambardella P. Early death in two sisters with Hennekam syndrome // Am. J. Med. Genet. 2000. 93. p. 181-183. 44. Scheuerle A.E., Sweed N.T., Timmons C.F., Smith E.D., Alcaraz W.A., Shinde D.N. An additional case of Hennekam lymphangiectasia-lymphedema syndrome caused by loss-of-function mutation in ADAMTS3 // Am J Med Genet A. 2018 Dec;176(12):2858-2861. 45. Shinwari K., Guojun L., Deryabina S.S., Bolkov M.A., Tuzankina I.A., et al. Predicting the Most Deleterious Missense Nonsynonymous Single-Nucleotide Polymorphisms of Hennekam Syndrome-Causing CCBE1 Gene, In Silico Analysis. ScientificWorldJournal. 2021 Jun 10;2021:6642626. 46. Shinwari K., Wu Y, Rehman HM, Xiao N, Bolkov M, Tuzankina I, Chereshnev V. In-silico assessment of high-risk non-synonymous SNPs in ADAMTS3 gene associated with Hennekam syndrome and their impact on protein stability and function // BMC Bioinformatics. 2023 Jun 15;24(1):251. 47. Sybile S., Froster U. G Microcephaly-lymphedema syndrome: report of a family with short stature as additional manifestation // Am. J. Med. Genet. 1998. 80(5). 506-509. 48. Tessarin G., Baronio M., Gazzurelli L., Rossi S., Chiarini M., et al. Hennekam syndrome due to a novel homozygous CCBE1 mutation presenting as pediatric-onset CVID //J Investig Allergol Clin Immunol. 2023 Feb 1:0. 49. Van Balkom I.D.C., Alders M., Allanson J., Bellini C., Frank U., et al. Lymphedema-lymphangiectasia-mental retardation (Hennekam) syndrome: a review // Am. J. Med. Genet.-2002.112.412-421. 50. Viswanathan P., Novak I. Intestinal Lymphangiestasia With Hennekam Syndrome // J Pediatr Gastroenterol Nutr. 2017 Dec;65(6):e133. 51. Williams M.S., Josephson K.D. Unusual Autosomal Recessive Lymphatic Anomalies in Two Unrelated Amish Families // American Journal of Medical Genetics. 1997. 73. 286–289. 52. Yasunaga M., Yamanaka C., Mayumi M., Momoi T., Mikawa H. Protein-losing gastroenteropathy with facial anomaly and growth retardation: a mild case of Hennekam syndrome // Am. J. Med. Genet. 1993. 45. p. 477-480. 53.Yamada T., Alpers D.H., Kalloo A.N., Kaplowitz N., Owyang C., Powell D.W. Hennekam lymphangiectasia In:. Text Book of Gastroenterology (5th ed). US: Wiley Blackwell; 2008. p.1101-2.
Number of Views: 30

Key words:

Bibliography link

Messova A.M., Akimzhanov K.D., Yurkovskaya O., Smail Ye.M., Abdrakhmanov S.T., Adilbaeva A.K., Karazhanova A.S. Hennekam syndrome: literature review // Nauka i Zdravookhranenie [Science & Healthcare]. 2023, (Vol.25) 3, pp. 208-213. DOI 10.34689/SH.2023.25.3.027

Авторизируйтесь для отправки комментариев