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Fryns syndrome phenotype caused by chromosome microdeletions at 15q26.2 and 8p23.1
  1. A Slavotinek1,
  2. S S Lee1,
  3. R Davis2,
  4. A Shrit3,
  5. K A Leppig4,
  6. J Rhim5,
  7. K Jasnosz6,
  8. D Albertson2,
  9. D Pinkel2
  1. 1Department of Pediatrics, University of California, San Francisco, 533 Parnassus St, Room U585P, San Francisco, CA 94143-0748, USA
  2. 2Comprehensive Cancer Center, Box 0808, University of California, San Francisco, San Francisco, CA 94143-0808, USA
  3. 3Department of Pathology, Miami Valley Hospital, Dayton, OH 45409, USA
  4. 4Genetic Services, Group Health Cooperative CMB-5, 201 16th Ave. E. CSB-A, Seattle, WA 98112, USA
  5. 5Department of Pathology, Group Health Cooperative, 125 16th Avenue E CSB-A, Seattle, WA 98112-5260, USA
  6. 6Department of Pathology and Laboratory Medicine, Allegheny General Hospital, 320 North East Avenue, Pittsburgh, PA 15212-4772, USA
  1. Correspondence to:
 A Slavotinek
 Department of Pediatrics, University of California, San Francisco, 533 Parnassus St, Room U585P, San Francisco, CA 94143-0748, USA; slavotiapeds.ucsf.edu

Abstract

Background: Fryns syndrome (FS) is the commonest autosomal recessive syndrome in which congenital diaphragmatic hernia (CDH) is a cardinal feature. It has been estimated that 10% of patients with CDH have FS. The autosomal recessive inheritance in FS contrasts with the sporadic inheritance for the majority of patients with CDH and renders the correct diagnosis critical for accurate genetic counselling. The cause of FS is unknown.

Methods: We have used array comparative genomic hybridisation (array CGH) to screen patients who have CDH and additional phenotypic anomalies consistent with FS for cryptic chromosome aberrations.

Results: We present three probands who were previously diagnosed with FS who had submicroscopic chromosome deletions detected by array CGH after normal karyotyping with G-banded chromosome analysis. Two female infants were found to have microdeletions involving chromosome band 15q26.2 and one male had a deletion of chromosome band 8p23.1.

Conclusions: We conclude that phenotypes similar to FS can be caused by submicroscopic chromosome deletions and that high resolution karyotyping, including array CGH if possible, should be performed prior to the diagnosis of FS to provide an accurate recurrence risk in patients with CDH and physical anomalies consistent with FS.

  • array CGH, array comparative genomic hybridisation
  • BAC, bacterial artificial chromosome
  • CCD, charge-cooled device
  • CDH, congenital diaphragmatic hernia
  • CHR, Committee for Human Subjects Research
  • CRL, crown-rump length
  • FISH, fluorescence in situ hybridisation
  • FS, Fryns syndrome
  • PCR, polymerase chain reaction
  • array comparative genomic hybridisation
  • congenital diaphragmatic hernia
  • Fryns syndrome
  • microdeletion
  • submicroscopic chromosome deletion

https://doi.org/10.1136/jmg.2004.028787

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    Footnotes

    • This work was supported by REAC grant number 36248-524269, University of California, San Francisco. We also acknowledge the Sandler Family Supporting Foundation for a Sandler Program in Basic Science/New Technology Resources Award to the Genomics Core Facility.

    • Competing interests: none declared

    • Ethics approval: The protocol used in this study was approved by the Committee for Human Subjects Research (CHR) at the University of California, San Francisco (UCSF; CHR number H41842-22157-02A).

      Statement regarding photographic reproduction: Signed permission for reproduction of photographs was obtained from a parent for each of the probands under protocol CHR number H41842-22157-02A at UCSF.

      Since the submission of this paper, additional case reports of diaphragmatic hernia associated with deletions at chromosome 15q26 have been published (Hengstschlaeger et al. Fetal Diagn Ther2004;(6):–2; Klaassens et al. Am J Hum Genet2005;(5):epub). A 5 Mb “critical interved” has been delineated for the diaphragmatic hernia causing gene by Klaasens et al between BACs RP11-152L20 and RP11-753A21 (2005).