Skip to main content
NCBI home page
Journal of Medical Genetics logoLink to Journal of Medical Genetics
. 1998 Sep;35(9):759–762. doi: 10.1136/jmg.35.9.759

Spastic paraplegia, optic atrophy, microcephaly with normal intelligence, and XY sex reversal: a new autosomal recessive syndrome?

A S Teebi 1, S Miller 1, H Ostrer 1, P Eydoux 1, C Colomb-Brockmann 1, K Oudjhane 1, G Watters 1
PMCID: PMC1051429  PMID: 9733035

Abstract

Two female sibs of first cousin Iranian parents were found to have the syndrome of spastic paraplegia, optic atrophy with poor vision, microcephaly, and normal cognitive development. Karyotype analysis showed a normal female constitution in one and a male constitution (46,XY) in the other. The XY female showed normal female external genitalia, normal uterus and tubes, and streak gonads. SRY gene sequencing was normal. We conclude that the present family probably represents a new autosomal recessive trait of pleiotropic effects including XY sex reversal and adds further evidence for the heterogeneity of spastic paraplegia syndromes as well as sex reversal syndromes.

Full text

PDF
759

Images in this article

759Image
on p.759
760Image
on p.760
760Image
on p.760
761Image
on p.761

Selected References

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

  1. Abdallat A., Davis S. M., Farrage J., McDonald W. I. Disordered pigmentation, spastic paraparesis and peripheral neuropathy in three siblings: a new neurocutaneous syndrome. J Neurol Neurosurg Psychiatry. 1980 Nov;43(11):962–966. doi: 10.1136/jnnp.43.11.962. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BRUYN G. W., WENT L. N. A SEX-LINKED HEREDO-DEGENERATIVE NEUROLOGICAL DISORDER, ASSOCIATED WITH LEBER'S OPTIC ATROPHY. I. CLINICAL STUDIES. J Neurol Sci. 1964 Jan-Feb;1(1):59–80. doi: 10.1016/0022-510x(64)90054-1. [DOI] [PubMed] [Google Scholar]
  3. Baar H. S., Gabriel A. M. Sex-linked spastic paraplegia. Am J Ment Defic. 1966 Jul;71(1):13–18. [PubMed] [Google Scholar]
  4. Bardoni B., Zanaria E., Guioli S., Floridia G., Worley K. C., Tonini G., Ferrante E., Chiumello G., McCabe E. R., Fraccaro M. A dosage sensitive locus at chromosome Xp21 is involved in male to female sex reversal. Nat Genet. 1994 Aug;7(4):497–501. doi: 10.1038/ng0894-497. [DOI] [PubMed] [Google Scholar]
  5. Bernstein R., Jenkins T., Dawson B., Wagner J., Dewald G., Koo G. C., Wachtel S. S. Female phenotype and multiple abnormalities in sibs with a Y chromosome and partial X chromosome duplication: H--Y antigen and Xg blood group findings. J Med Genet. 1980 Aug;17(4):291–300. doi: 10.1136/jmg.17.4.291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cameron F. J., Sinclair A. H. Mutations in SRY and SOX9: testis-determining genes. Hum Mutat. 1997;9(5):388–395. doi: 10.1002/(SICI)1098-1004(1997)9:5<388::AID-HUMU2>3.0.CO;2-0. [DOI] [PubMed] [Google Scholar]
  7. Crocker M., Coghill S. B., Cortinho R. An unbalanced autosomal translocation (7;9) associated with feminization. Clin Genet. 1988 Jul;34(1):70–73. doi: 10.1111/j.1399-0004.1988.tb02618.x. [DOI] [PubMed] [Google Scholar]
  8. Cross H. E., McKusick V. A., Breen W. A new oculocerebral syndrome with hypopigmentation. J Pediatr. 1967 Mar;70(3):398–406. doi: 10.1016/s0022-3476(67)80137-9. [DOI] [PubMed] [Google Scholar]
  9. Daras M., Tuchman A. J., David S. Familial spinocerebellar ataxia with skin hyperpigmentation. J Neurol Neurosurg Psychiatry. 1983 Aug;46(8):743–744. doi: 10.1136/jnnp.46.8.743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Donnelly A., Colley A., Crimmins D., Mulley J. A novel mutation in exon 6 (F236S) of the proteolipid protein gene is associated with spastic paraplegia. Hum Mutat. 1996;8(4):384–385. doi: 10.1002/(SICI)1098-1004(1996)8:4<384::AID-HUMU17>3.0.CO;2-Z. [DOI] [PubMed] [Google Scholar]
  11. Fink J. K., Heiman-Patterson T., Bird T., Cambi F., Dubé M. P., Figlewicz D. A., Fink J. K., Haines J. L., Heiman-Patterson T., Hentati A. Hereditary spastic paraplegia: advances in genetic research. Hereditary Spastic Paraplegia Working group. Neurology. 1996 Jun;46(6):1507–1514. doi: 10.1212/wnl.46.6.1507. [DOI] [PubMed] [Google Scholar]
  12. Fitzsimmons J. S., Guilbert P. R. Spastic paraplegia associated with brachydactyly and cone shaped epiphyses. J Med Genet. 1987 Nov;24(11):702–705. doi: 10.1136/jmg.24.11.702. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gigli G. L., Diomedi M., Bernardi G., Placidi F., Marciani M. G., Calia E., Maschio M. C., Neri G. Spastic paraplegia, epilepsy, and mental retardation in several members of a family: a novel genetic disorder. Am J Med Genet. 1993 Mar 15;45(6):711–716. doi: 10.1002/ajmg.1320450610. [DOI] [PubMed] [Google Scholar]
  14. Goldblatt J., Ballo R., Sachs B., Moosa A. X-linked spastic paraplegia: evidence for homogeneity with a variable phenotype. Clin Genet. 1989 Feb;35(2):116–120. doi: 10.1111/j.1399-0004.1989.tb02915.x. [DOI] [PubMed] [Google Scholar]
  15. Gordon A. M., Capute A. J., Konigsmark B. W. Progressive quadriparesis, mental retardation, retinitis pigmentosa, and hearing loss: report of two sibs. Johns Hopkins Med J. 1976 Apr;138(4):142–145. [PubMed] [Google Scholar]
  16. Greenberg F., Gresik M. V., Carpenter R. J., Law S. W., Hoffman L. P., Ledbetter D. H. The Gardner-Silengo-Wachtel or genito-palato-cardiac syndrome: male pseudohermaphroditism with micrognathia, cleft palate, and conotruncal cardiac defect. Am J Med Genet. 1987 Jan;26(1):59–64. doi: 10.1002/ajmg.1320260111. [DOI] [PubMed] [Google Scholar]
  17. Gubbay J., Collignon J., Koopman P., Capel B., Economou A., Münsterberg A., Vivian N., Goodfellow P., Lovell-Badge R. A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes. Nature. 1990 Jul 19;346(6281):245–250. doi: 10.1038/346245a0. [DOI] [PubMed] [Google Scholar]
  18. Gustavson K. H., Modrzewska K., Erikson A. Hereditary spastic diplegia with mental retardation in two young siblings. Clin Genet. 1989 Dec;36(6):439–441. doi: 10.1111/j.1399-0004.1989.tb03373.x. [DOI] [PubMed] [Google Scholar]
  19. Harding A. E. Classification of the hereditary ataxias and paraplegias. Lancet. 1983 May 21;1(8334):1151–1155. doi: 10.1016/s0140-6736(83)92879-9. [DOI] [PubMed] [Google Scholar]
  20. Harding A. E. Hereditary "pure" spastic paraplegia: a clinical and genetic study of 22 families. J Neurol Neurosurg Psychiatry. 1981 Oct;44(10):871–883. doi: 10.1136/jnnp.44.10.871. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Harding A. E. Hereditary spastic paraplegias. Semin Neurol. 1993 Dec;13(4):333–336. doi: 10.1055/s-2008-1041143. [DOI] [PubMed] [Google Scholar]
  22. Hawkins J. R., Taylor A., Goodfellow P. N., Migeon C. J., Smith K. D., Berkovitz G. D. Evidence for increased prevalence of SRY mutations in XY females with complete rather than partial gonadal dysgenesis. Am J Hum Genet. 1992 Nov;51(5):979–984. [PMC free article] [PubMed] [Google Scholar]
  23. Hennekam R. C. Spastic paraplegia, dysarthria, brachydactyly, and cone shaped epiphyses: confirmation of the Fitzsimmons syndrome. J Med Genet. 1994 Mar;31(3):251–252. doi: 10.1136/jmg.31.3.251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. JAMPEL R. S., OKAZAKI H., BERNSTEIN H. Ophthalmoplegia and retinal degeneration associated with spinocerebellar ataxia. Arch Ophthalmol. 1961 Aug;66:247–259. doi: 10.1001/archopht.1961.00960010249017. [DOI] [PubMed] [Google Scholar]
  25. Jancar J. Ectrodactyly, spastic paraplegia and mental retardation. J Ment Defic Res. 1967 Sep;11(3):207–211. doi: 10.1111/j.1365-2788.1967.tb00221.x. [DOI] [PubMed] [Google Scholar]
  26. Joshita Y., Atsumi T., Miyatake T. [Two siblings with spastic paraplegia, optic atrophy and peripheral neuropathy]. Rinsho Shinkeigaku. 1982 Oct;22(10):901–908. [PubMed] [Google Scholar]
  27. Kenwrick S., Ionasescu V., Ionasescu G., Searby C., King A., Dubowitz M., Davies K. E. Linkage studies of X-linked recessive spastic paraplegia using DNA probes. Hum Genet. 1986 Jul;73(3):264–266. doi: 10.1007/BF00401241. [DOI] [PubMed] [Google Scholar]
  28. Keppen L. D., Leppert M. F., O'Connell P., Nakamura Y., Stauffer D., Lathrop M., Lalouel J. M., White R. Etiological heterogeneity in X-linked spastic paraplegia. Am J Hum Genet. 1987 Nov;41(5):933–943. [PMC free article] [PubMed] [Google Scholar]
  29. Landrigan P. J., Berenberg W., Bresnan M. Behr's syndrome: familial optic atrophy, spastic diplegia and ataxia. Dev Med Child Neurol. 1973 Feb;15(1):41–47. doi: 10.1111/j.1469-8749.1973.tb04864.x. [DOI] [PubMed] [Google Scholar]
  30. Lison M., Kornbrut B., Feinstein A., Hiss Y., Boichis H., Goodman R. M. Progressive spastic paraparesis, vitiligo, premature graying, and distinct facial appearance: a new genetic syndrome in 3 sibs. Am J Med Genet. 1981;9(4):351–357. doi: 10.1002/ajmg.1320090411. [DOI] [PubMed] [Google Scholar]
  31. Mahloudji M., Chuke P. O. Familial spastic paraplegia with retinal degeneration. Johns Hopkins Med J. 1968 Sep;123(3):142–144. [PubMed] [Google Scholar]
  32. McNamara J. O., Curran J. R., Itabashi H. H. Congenital ichthyosis with spastic paraplegia of adult onset. Arch Neurol. 1975 Oct;32(10):699–701. doi: 10.1001/archneur.1975.00490520069011. [DOI] [PubMed] [Google Scholar]
  33. Mukamel M., Weitz R., Metzker A., Varsano I. Spastic paraparesis, mental retardation, and cutaneous pigmentation disorder. A new syndrome. Am J Dis Child. 1985 Nov;139(11):1090–1092. doi: 10.1001/archpedi.1985.02140130028023. [DOI] [PubMed] [Google Scholar]
  34. Nyberg-Hansen R., Refsum S. Spastic paraparesis associated with optic atrophy in monozygotic twins. Acta Neurol Scand Suppl. 1972;51:261–263. [PubMed] [Google Scholar]
  35. O'Neill B. P., Swanson J. W., Brown F. R., 3rd, Griffin J. W., Moser H. W. Familial spastic paraparesis: an adrenoleukodystrophy phenotype? Neurology. 1985 Aug;35(8):1233–1235. doi: 10.1212/wnl.35.8.1233. [DOI] [PubMed] [Google Scholar]
  36. Ogata T., Hawkins J. R., Taylor A., Matsuo N., Hata J., Goodfellow P. N. Sex reversal in a child with a 46,X,Yp+ karyotype: support for the existence of a gene(s), located in distal Xp, involved in testis formation. J Med Genet. 1992 Apr;29(4):226–230. doi: 10.1136/jmg.29.4.226. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. ROE P. F. HEREDITARY SPASTIC PARAPLEGIA. J Neurol Neurosurg Psychiatry. 1963 Dec;26:516–519. doi: 10.1136/jnnp.26.6.516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Reid E. Pure hereditary spastic paraplegia. J Med Genet. 1997 Jun;34(6):499–503. doi: 10.1136/jmg.34.6.499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Sjaastad O., Berstad J., Gjesdahl P., Gjessing L. Homocarnosinosis. 2. A familial metabolic disorder associated with spastic paraplegia, progressive mental deficiency, and retinal pigmentation. Acta Neurol Scand. 1976 Apr;53(4):275–290. doi: 10.1111/j.1600-0404.1976.tb04348.x. [DOI] [PubMed] [Google Scholar]
  40. Stoll C., Huber C., Alembik Y., Terrade E., Maitrot D. Dandy-Walker variant malformation, spastic paraplegia, and mental retardation in two sibs. Am J Med Genet. 1990 Sep;37(1):124–127. doi: 10.1002/ajmg.1320370129. [DOI] [PubMed] [Google Scholar]
  41. Young I. D., Zuccollo J. M., Maltby E. L., Broderick N. J. Campomelic dysplasia associated with a de novo 2q;17q reciprocal translocation. J Med Genet. 1992 Apr;29(4):251–252. doi: 10.1136/jmg.29.4.251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Zlotogora J. Mental retardation, spasticity, and transverse limb defects. Am J Med Genet. 1987 Jan;26(1):221–223. doi: 10.1002/ajmg.1320260133. [DOI] [PubMed] [Google Scholar]

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

RESOURCES