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The article presents the clinical and genetic characteristics of a patient with Knobloch syndrome caused by the previously indescried combination of mutations in the compound heterozygous state c.4054_4055delCT / c.1469-2A>G in the gene COL18A1. The peculiarity of the presented case is the absence of symptoms of central nervous system damage, found in most patients with this syndrome.

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About the authors

Olga V. Khlebnikova

Research Centre for Medical Genetics

Moscow, 115478, Russian Federation
leading Researcher of the Research Centre for Medical Genetics, Moscow

E. L Dadali

Research Centre for Medical Genetics

Moscow, 115478, Russian Federation

L. A Bessonova

«Genomed», Centre for Medical Genetics

Moscow, 115478, Russian Federation

F. A Konovalov

Research Centre for Medical Genetics

Moscow, 115478, Russian Federation


  1. Хлебникова О.В., Дадали Е.Л. Наследственная патология органа зрения. Под ред. акад. РАМН Е.К Гинтера. М., 2014: с. 304.УДК 617.7-007. ISBN 978-5-91902-025-7. ББК56.7.
  2. McKusick V.A. Online Mendelian inheritance in man. Catalogs of Human Genes and Genetic Disorders. Baltimore; London: John Hopkins, Univ. press. 2010.
  3. Knobloch W.H., Layer J.M. Retinal detachment and encephalocele. J. Pediat. Ophthal. 1971; 8: 181-4.
  4. Hoyme H. E., Seaver L. H., Joffe L., Spark R. P., Smith B. Congenital scalp defects and vitreoretinal degeneration: confirmation of the Knobloch syndrome. (Abstract) Am. J. Hum. Genet. 1992; 51 (suppl.): A98 only.
  5. Czeizel A.E., Goblyos P., Kustos G., Mester E., Paraicz E. The second report of Knobloch syndrome. Am. J. Med. Genet. 1992; 42: 777-9.
  6. Kliemann S.E., Waetge R.T.L., Suzuki O.T., Passos-Bueno M.R., Rosemberg S. Evidence of neuronal migration disorders in Knobloch syndrome: clinical and molecular analysis of two novel families. Am. J. Med. Genet. 2003; 119A: 15-9.
  7. Cohen M.M., Jr. Lemire R.J. Syndromes with cephaloceles. 1982; Teratology 25: 161-72.
  8. Khaliq S., Abid A., White D.R.A., Johnson C.A., Ismail M., Khan A., Ayub Q., Sultana S., Maher E.R., Mehdi S.Q. Mapping of a novel type III variant of Knobloch syndrome (KNO3) to chromosome 17q11.2. Am. J. Med. Genet. 2007; 143A: 2768-74.
  9. Seaver LH, Joffe L, Spark RP, Smith BL, Hoyme HE. Congenital scalp defects and vitreoretinal degeneration: redefining the Knobloch syndrome. Am. J. Med. Genet. 1993; 46: 203-8.
  10. Sniderman L.C., Koenekoop R.K., O’Gorman A.M., Usher R.H., Sufrategui M.R., Moroz B., Watters G.V., Der Kaloustian V.M. Knobloch syndrome involving midline scalp defect of the frontal region. Am. J. Med. Genet. 2000; 90: 146-9.
  11. Wilson C., Aftimos S., Pereira A., McKay R. Report of two sibs with Knobloch syndrome (encephalocele and viteroretinal (sic) degeneration) and other anomalies. Am. J. Med. Genet. 1998; 78: 286-90.
  12. Aldahmesh M.A., Khan A.O., Mohamed J.Y., Alkuraya H., Ahmed H., Bobis S., Al-Mesfer S., Alkuraya F.S. Identification of ADAMTS18 as a gene mutated in Knobloch syndrome. J. Med. Genet. 2011; 48: 597-601.
  13. Keren B., Suzuki O.T., Gerard-Blanluet M., Bremond-Gignac D., Elmaleh M., Titomanlio L., Delezoide A-L., Passos-Bueno M.R., Verloes A. CNS malformations in Knobloch syndrome with splice mutation in COL18A1 gene. (Letter) Am. J. Med. Genet. 2007; 143A: 1514-8.
  14. Paisan-Ruiz C., Scopes G., Lee P., Houlden H. Homozygosity mapping through whole genome analysis identifies a COL18A1 mutation in an Indian family presenting with an autosomal recessive neurological disorder. Am. J. Med. Genet. 2009; 150B: 993-7.
  15. Joyce S., Tee L., Abid A., Khaliq S., Mehdi S.Q., Maher E.R. Locus heterogeneity and Knobloch syndrome. (Letter). Am. J. Med. Genet. 2010; 152A: 2880-1.
  16. Sertie A.L., Quimby M., Moreira E.S., Murray J., Zatz M., Antonarakis S.E., Passos-Bueno M.R. A gene which causes severe ocular alterations and occipital encephalocele (Knobloch syndrome) is mapped to 21q22.3. Hum. Molec. Genet. 1996; 5: 843-7.
  17. Sertie A.L., Sossi V., Camargo A.A., Zatz M., Brahe C., Passos-Bueno M.R. Collagen XVIII, containing an endogenous inhibitor of angiogenesis and tumor growth, plays a critical role in the maintenance of retinal structure and in neural tube closure (Knobloch syndrome). Hum. Molec. Genet. 2000; 9: 2051-8.
  18. Passos-Bueno M.R., Marie S.K., Monteiro M., Neustein I., Whittle M.R., Vainzof M., Zatz M. Knobloch syndrome in a large Brazilian consanguineous family: confirmation of autosomal recessive inheritance. Am. J. Med. Genet. 1994: 52: 170-3.
  19. Menzel O., Bekkeheien R.C.J, Reymond A., Fukai N., Boye E., Kosztolanyi G., Aftimos S., Deutsch S., Scott H.S., Olsen B.R., Antonarakis S.E., Guipponi M. Knobloch syndrome: novel mutations in COL18A1, evidence for genetic heterogeneity, and a functionally impaired polymorphism in endostatin. Hum. Mutat. 2004; 23: 77-84.
  20. Najmabadi H., Hu H., Garshasbi M., Zemojtel T., Abedini S.S., Chen W., Hosseini M., Behjati F., Haas S., Jamali P., Zecha A., Mohseni M., and 33 others. Deep sequencing reveals 50 novel genes for recessive cognitive disorders. Nature. 2011; 478: 57-63.
  21. Aldahmesh M.A., Khan A.O., Mohamed J.Y., Levin A.V., Wuthisiri W., Lynch S., McCreery K., Alkuraya F.S. No evidence for locus heterogeneity in Knobloch syndrome. (Letter). J. Med. Genet. , 2013; 50: 565-6.



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