Skip to main content
PMC home page
Journal of Medical Genetics logoLink to Journal of Medical Genetics
. 1997 Mar;34(3):256–260. doi: 10.1136/jmg.34.3.256

Tuberous sclerosis complex: neonatal deaths in three of four children of consanguineous, non-expressing parents.

M Ruggieri 1, C Carbonara 1, G Magro 1, N Migone 1, S Grasso 1, A Tinè 1, L Pavone 1, M R Gomez 1
PMCID: PMC1050905  PMID: 9132502

Abstract

We describe here four sibs, born to consanguineous, healthy, asymptomatic parents. Three of these infants had a rapidly fatal course in the neonatal period; death was attributed to congestive heart failure with radiographic evidence of cardiomegaly in all of them. Necropsy was done in only one of them and showed the typical findings of tuberous sclerosis complex (TSC) in the central nervous system (CNS), kidneys, heart, and liver. The fourth sib, currently 2 years old, also has typical signs of TSC, namely hypomelanotic skin macules and calcified subependymal nodules. Both parents and a living maternal grandmother had appropriate examination, which included skin inspection under Wood's lamp, dental examination, fundoscopy, echocardiography, abdominal and renal ultrasound, and head CT and MRI scans, and no signs of TSC were found in either parent or in the only living grandmother. By history alone there is no other relative with signs or symptoms suggestive of TSC. Linkage analysis and loss of heterozygosity (LOH) investigations on a variety of lesions obtained from postmortem and tissue or blood specimens from all available family members studied failed to identify a microdeletion in the chromosomal regions where TSC genes are located. It is very unusual that in a single TSC family there were three consecutive neonatal deaths, and very likely that all had cardiac rhabdomyomas. Moreover, to the best of our knowledge, there are no previous reports of TSC families with more than one affected sib, unusually severe manifestations of the disease, and completely normal, consanguineous parents.

Full text

PDF
256

Images in this article

258Image
on p.258
258Image
on p.258
259Image
on p.259
259Image
on p.259

Selected References

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

  1. Bulbul Z. R., Rosenthal D., Brueckner M. Genetic aspects of heart disease in the newborn. Semin Perinatol. 1993 Apr;17(2):61–75. [PubMed] [Google Scholar]
  2. Carbonara C., Longa L., Grosso E., Mazzucco G., Borrone C., Garrè M. L., Brisigotti M., Filippi G., Scabar A., Giannotti A. Apparent preferential loss of heterozygosity at TSC2 over TSC1 chromosomal region in tuberous sclerosis hamartomas. Genes Chromosomes Cancer. 1996 Jan;15(1):18–25. doi: 10.1002/(SICI)1098-2264(199601)15:1<18::AID-GCC3>3.0.CO;2-7. [DOI] [PubMed] [Google Scholar]
  3. Fenoglio J. J., Jr, MCAllister H. A., Jr, Ferrans V. J. Cardiac rhabdomyoma: a clinicopathologic and electron microscopic study. Am J Cardiol. 1976 Aug;38(2):241–251. doi: 10.1016/0002-9149(76)90157-0. [DOI] [PubMed] [Google Scholar]
  4. Fryer A. E., Chalmers A., Connor J. M., Fraser I., Povey S., Yates A. D., Yates J. R., Osborne J. P. Evidence that the gene for tuberous sclerosis is on chromosome 9. Lancet. 1987 Mar 21;1(8534):659–661. doi: 10.1016/s0140-6736(87)90416-8. [DOI] [PubMed] [Google Scholar]
  5. Gomez M. R. Phenotypes of the tuberous sclerosis complex with a revision of diagnostic criteria. Ann N Y Acad Sci. 1991;615:1–7. doi: 10.1111/j.1749-6632.1991.tb37742.x. [DOI] [PubMed] [Google Scholar]
  6. Grasso S., Manusia M., Sciacca F. Unusual liver lesion in tuberous sclerosis. Arch Pathol Lab Med. 1982 Jan;106(1):49–49. [PubMed] [Google Scholar]
  7. Harding C. O., Pagon R. A. Incidence of tuberous sclerosis in patients with cardiac rhabdomyoma. Am J Med Genet. 1990 Dec;37(4):443–446. doi: 10.1002/ajmg.1320370402. [DOI] [PubMed] [Google Scholar]
  8. Jówiak S., Pedich M., Rajszys P., Michalowicz R. Incidence of hepatic hamartomas in tuberous sclerosis. Arch Dis Child. 1992 Nov;67(11):1363–1365. doi: 10.1136/adc.67.11.1363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kandt R. S., Haines J. L., Smith M., Northrup H., Gardner R. J., Short M. P., Dumars K., Roach E. S., Steingold S., Wall S. Linkage of an important gene locus for tuberous sclerosis to a chromosome 16 marker for polycystic kidney disease. Nat Genet. 1992 Sep;2(1):37–41. doi: 10.1038/ng0992-37. [DOI] [PubMed] [Google Scholar]
  10. Kobayashi T., Hirayama Y., Kobayashi E., Kubo Y., Hino O. A germline insertion in the tuberous sclerosis (Tsc2) gene gives rise to the Eker rat model of dominantly inherited cancer. Nat Genet. 1995 Jan;9(1):70–74. doi: 10.1038/ng0195-70. [DOI] [PubMed] [Google Scholar]
  11. Mushlin A. I., Mooney C., Grow V., Phelps C. E. The value of diagnostic information to patients with suspected multiple sclerosis. Rochester-Toronto MRI Study Group. Arch Neurol. 1994 Jan;51(1):67–72. doi: 10.1001/archneur.1994.00540130093017. [DOI] [PubMed] [Google Scholar]
  12. Nir A., Tajik A. J., Freeman W. K., Seward J. B., Offord K. P., Edwards W. D., Mair D. D., Gomez M. R. Tuberous sclerosis and cardiac rhabdomyoma. Am J Cardiol. 1995 Aug 15;76(5):419–421. doi: 10.1016/s0002-9149(99)80117-9. [DOI] [PubMed] [Google Scholar]
  13. Povey S., Burley M. W., Attwood J., Benham F., Hunt D., Jeremiah S. J., Franklin D., Gillett G., Malas S., Robson E. B. Two loci for tuberous sclerosis: one on 9q34 and one on 16p13. Ann Hum Genet. 1994 May;58(Pt 2):107–127. doi: 10.1111/j.1469-1809.1994.tb01881.x. [DOI] [PubMed] [Google Scholar]
  14. Shepherd C. W., Gomez M. R., Lie J. T., Crowson C. S. Causes of death in patients with tuberous sclerosis. Mayo Clin Proc. 1991 Aug;66(8):792–796. doi: 10.1016/s0025-6196(12)61196-3. [DOI] [PubMed] [Google Scholar]
  15. Verhoef S., Vrtel R., van Essen T., Bakker L., Sikkens E., Halley D., Lindhout D., van den Ouweland A. Somatic mosaicism and clinical variation in tuberous sclerosis complex. Lancet. 1995 Jan 21;345(8943):202–202. doi: 10.1016/s0140-6736(95)90213-9. [DOI] [PubMed] [Google Scholar]
  16. Webb D. W., Osborne J. P. Non-penetrance in tuberous sclerosis. J Med Genet. 1991 Jun;28(6):417–419. doi: 10.1136/jmg.28.6.417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Webb D. W., Osborne J. P. Tuberous sclerosis. Arch Dis Child. 1995 Jun;72(6):471–474. doi: 10.1136/adc.72.6.471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Webb D. W., Thomas R. D., Osborne J. P. Cardiac rhabdomyomas and their association with tuberous sclerosis. Arch Dis Child. 1993 Mar;68(3):367–370. doi: 10.1136/adc.68.3.367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Wilson P. J., Ramesh V., Kristiansen A., Bove C., Jozwiak S., Kwiatkowski D. J., Short M. P., Haines J. L. Novel mutations detected in the TSC2 gene from both sporadic and familial TSC patients. Hum Mol Genet. 1996 Feb;5(2):249–256. doi: 10.1093/hmg/5.2.249. [DOI] [PubMed] [Google Scholar]
  20. Zeller J., Friedmann D., Clerici T., Revuz J. The significance of a single periungual fibroma: report of seven cases. Arch Dermatol. 1995 Dec;131(12):1465–1466. doi: 10.1001/archderm.131.12.1465b. [DOI] [PubMed] [Google Scholar]

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

RESOURCES