Skip to main content
NCBI home page
Journal of Medical Genetics logoLink to Journal of Medical Genetics
. 1998 Sep;35(9):763–766. doi: 10.1136/jmg.35.9.763

Familial craniosynostosis, anal anomalies, and porokeratosis: CAP syndrome.

N Flanagan 1, S A Boyadjiev 1, J Harper 1, L Kyne 1, M Earley 1, R Watson 1, E W Jabs 1, M T Geraghty 1
PMCID: PMC1051430  PMID: 9733036

Abstract

We report on the occurrence of coronal craniosynostosis, anal anomalies, and porokeratosis in two male sibs. A third male sib was phenotypically normal as were the parents. The occurrence of these three clinical features has, to our knowledge, not been reported before. Cutaneous or anal anomalies or both have been reported in a number of syndromes associated with craniosynostosis, including Crouzon, Pfeiffer, Apert, and Beare-Stevenson syndromes. These syndromes are associated with mutations in the fibroblast growth factor receptor genes FGFR1, FGFR2, and FGFR3. They are inherited in an autosomal dominant fashion. In contrast, the cases we report do not carry any of the common FGFR mutations and the pedigree suggests autosomal or X linked recessive inheritance.

Full text

PDF
763

Images in this article

763Image
on p.763
764Image
on p.764
764Image
on p.764
765Image
on p.765
765Image
on p.765
765Image
on p.765

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson D. E., Chernosky M. E. Disseminated superficial actinic porokeratosis. Genetic aspects. Arch Dermatol. 1969 Apr;99(4):408–412. [PubMed] [Google Scholar]
  2. Beare J. M., Dodge J. A., Nevin N. C. Cutis gyratum, acanthosis nigricans and other congenital anomalies. A new syndrome. Br J Dermatol. 1969 Apr;81(4):241–247. [PubMed] [Google Scholar]
  3. Bellus G. A., Gaudenz K., Zackai E. H., Clarke L. A., Szabo J., Francomano C. A., Muenke M. Identical mutations in three different fibroblast growth factor receptor genes in autosomal dominant craniosynostosis syndromes. Nat Genet. 1996 Oct;14(2):174–176. doi: 10.1038/ng1096-174. [DOI] [PubMed] [Google Scholar]
  4. Howard T. D., Paznekas W. A., Green E. D., Chiang L. C., Ma N., Ortiz de Luna R. I., Garcia Delgado C., Gonzalez-Ramos M., Kline A. D., Jabs E. W. Mutations in TWIST, a basic helix-loop-helix transcription factor, in Saethre-Chotzen syndrome. Nat Genet. 1997 Jan;15(1):36–41. doi: 10.1038/ng0197-36. [DOI] [PubMed] [Google Scholar]
  5. Jabs E. W., Li X., Scott A. F., Meyers G., Chen W., Eccles M., Mao J. I., Charnas L. R., Jackson C. E., Jaye M. Jackson-Weiss and Crouzon syndromes are allelic with mutations in fibroblast growth factor receptor 2. Nat Genet. 1994 Nov;8(3):275–279. doi: 10.1038/ng1194-275. [DOI] [PubMed] [Google Scholar]
  6. Judge M. R., Michaels M., Sams V. R., David T. J., Harper J. I. Disseminated porokeratosis in an infant with craniosynostosis. Br J Dermatol. 1990 Aug;123(2):249–254. doi: 10.1111/j.1365-2133.1990.tb01855.x. [DOI] [PubMed] [Google Scholar]
  7. Lajeunie E., Ma H. W., Bonaventure J., Munnich A., Le Merrer M., Renier D. FGFR2 mutations in Pfeiffer syndrome. Nat Genet. 1995 Feb;9(2):108–108. doi: 10.1038/ng0295-108. [DOI] [PubMed] [Google Scholar]
  8. Meyers G. A., Orlow S. J., Munro I. R., Przylepa K. A., Jabs E. W. Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans. Nat Genet. 1995 Dec;11(4):462–464. doi: 10.1038/ng1295-462. [DOI] [PubMed] [Google Scholar]
  9. Muenke M., Schell U., Hehr A., Robin N. H., Losken H. W., Schinzel A., Pulleyn L. J., Rutland P., Reardon W., Malcolm S. A common mutation in the fibroblast growth factor receptor 1 gene in Pfeiffer syndrome. Nat Genet. 1994 Nov;8(3):269–274. doi: 10.1038/ng1194-269. [DOI] [PubMed] [Google Scholar]
  10. Oldridge M., Wilkie A. O., Slaney S. F., Poole M. D., Pulleyn L. J., Rutland P., Hockley A. D., Wake M. J., Goldin J. H., Winter R. M. Mutations in the third immunoglobulin domain of the fibroblast growth factor receptor-2 gene in Crouzon syndrome. Hum Mol Genet. 1995 Jun;4(6):1077–1082. doi: 10.1093/hmg/4.6.1077. [DOI] [PubMed] [Google Scholar]
  11. Orlow S. J. Cutaneous findings in craniofacial malformation syndromes. Arch Dermatol. 1992 Oct;128(10):1379–1386. [PubMed] [Google Scholar]
  12. Orr-Urtreger A., Bedford M. T., Burakova T., Arman E., Zimmer Y., Yayon A., Givol D., Lonai P. Developmental localization of the splicing alternatives of fibroblast growth factor receptor-2 (FGFR2). Dev Biol. 1993 Aug;158(2):475–486. doi: 10.1006/dbio.1993.1205. [DOI] [PubMed] [Google Scholar]
  13. Park W. J., Meyers G. A., Li X., Theda C., Day D., Orlow S. J., Jones M. C., Jabs E. W. Novel FGFR2 mutations in Crouzon and Jackson-Weiss syndromes show allelic heterogeneity and phenotypic variability. Hum Mol Genet. 1995 Jul;4(7):1229–1233. doi: 10.1093/hmg/4.7.1229. [DOI] [PubMed] [Google Scholar]
  14. Park W. J., Theda C., Maestri N. E., Meyers G. A., Fryburg J. S., Dufresne C., Cohen M. M., Jr, Jabs E. W. Analysis of phenotypic features and FGFR2 mutations in Apert syndrome. Am J Hum Genet. 1995 Aug;57(2):321–328. [PMC free article] [PubMed] [Google Scholar]
  15. Przylepa K. A., Paznekas W., Zhang M., Golabi M., Bias W., Bamshad M. J., Carey J. C., Hall B. D., Stevenson R., Orlow S. Fibroblast growth factor receptor 2 mutations in Beare-Stevenson cutis gyrata syndrome. Nat Genet. 1996 Aug;13(4):492–494. doi: 10.1038/ng0896-492. [DOI] [PubMed] [Google Scholar]
  16. Reardon W., Winter R. M., Rutland P., Pulleyn L. J., Jones B. M., Malcolm S. Mutations in the fibroblast growth factor receptor 2 gene cause Crouzon syndrome. Nat Genet. 1994 Sep;8(1):98–103. doi: 10.1038/ng0994-98. [DOI] [PubMed] [Google Scholar]
  17. Reddy B. S., Garg B. R., Padiyar N. V., Krishnaram A. S. An unusual association of acanthosis nigricans and Crouzon's disease--a case report. J Dermatol. 1985 Feb;12(1):85–90. doi: 10.1111/j.1346-8138.1985.tb01542.x. [DOI] [PubMed] [Google Scholar]
  18. Reed R. J., Leone P. Porokeratosis--a mutant clonal keratosis of the epidermis. I. Histogenesis. Arch Dermatol. 1970 Mar;101(3):340–347. [PubMed] [Google Scholar]
  19. Rutland P., Pulleyn L. J., Reardon W., Baraitser M., Hayward R., Jones B., Malcolm S., Winter R. M., Oldridge M., Slaney S. F. Identical mutations in the FGFR2 gene cause both Pfeiffer and Crouzon syndrome phenotypes. Nat Genet. 1995 Feb;9(2):173–176. doi: 10.1038/ng0295-173. [DOI] [PubMed] [Google Scholar]
  20. Scappaticci S., Lambiase S., Orecchia G., Fraccaro M. Clonal chromosome abnormalities with preferential involvement of chromosome 3 in patients with porokeratosis of Mibelli. Cancer Genet Cytogenet. 1989 Nov;43(1):89–94. doi: 10.1016/0165-4608(89)90131-3. [DOI] [PubMed] [Google Scholar]
  21. Schamroth J. M., Zlotogorski A., Gilead L. Porokeratosis of Mibelli. Overview and review of the literature. Acta Derm Venereol. 1997 May;77(3):207–213. doi: 10.2340/0001555577207213. [DOI] [PubMed] [Google Scholar]
  22. Shimamoto Y., Shimamoto H. Differentiation of disseminated superficial actinic porokeratosis from the superficial disseminated eruptive form of porokeratosis of Mibelli. Cutis. 1988 Oct;42(4):345–348. [PubMed] [Google Scholar]
  23. Solomon L. M., Fretzin D., Pruzansky S. Pilosebaceous abnormalities in Apert's syndrome. Arch Dermatol. 1970 Oct;102(4):381–385. [PubMed] [Google Scholar]
  24. Wade T. R., Ackerman A. B. Cornoid lamellation. A histologic reaction pattern. Am J Dermatopathol. 1980 Spring;2(1):5–15. doi: 10.1097/00000372-198000210-00002. [DOI] [PubMed] [Google Scholar]
  25. Walther L. Parakeratosis Mibelli bei Mongolismus und multiplen Missbildungen. Hautarzt. 1966 Aug;17(8):363–365. [PubMed] [Google Scholar]
  26. Werner S., Smola H., Liao X., Longaker M. T., Krieg T., Hofschneider P. H., Williams L. T. The function of KGF in morphogenesis of epithelium and reepithelialization of wounds. Science. 1994 Nov 4;266(5186):819–822. doi: 10.1126/science.7973639. [DOI] [PubMed] [Google Scholar]
  27. Wilkes D., Rutland P., Pulleyn L. J., Reardon W., Moss C., Ellis J. P., Winter R. M., Malcolm S. A recurrent mutation, ala391glu, in the transmembrane region of FGFR3 causes Crouzon syndrome and acanthosis nigricans. J Med Genet. 1996 Sep;33(9):744–748. doi: 10.1136/jmg.33.9.744. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wilkie A. O., Slaney S. F., Oldridge M., Poole M. D., Ashworth G. J., Hockley A. D., Hayward R. D., David D. J., Pulleyn L. J., Rutland P. Apert syndrome results from localized mutations of FGFR2 and is allelic with Crouzon syndrome. Nat Genet. 1995 Feb;9(2):165–172. doi: 10.1038/ng0295-165. [DOI] [PubMed] [Google Scholar]
  29. el Ghouzzi V., Le Merrer M., Perrin-Schmitt F., Lajeunie E., Benit P., Renier D., Bourgeois P., Bolcato-Bellemin A. L., Munnich A., Bonaventure J. Mutations of the TWIST gene in the Saethre-Chotzen syndrome. Nat Genet. 1997 Jan;15(1):42–46. doi: 10.1038/ng0197-42. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Medical Genetics are provided here courtesy of BMJ Publishing Group

RESOURCES