Skip to main content
Log in

Adult fragile X syndrome

Clinico-neuropathologic findings

  • Original Works
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Summary

Fragile X syndrome [fra (X)] is currently accepted as the second most frequent chromosomal disorder associated with developmental disability. Although next to Down syndrome in frequency, no postmortem studies of confirmed adult cases had been reported.

The autopsy examination of a 62-year-old, moderately retarded man with the fra (X) syndrome confirmed the preferential involvement of cerebral and testicular structures in this disorder.Dendritic spine abnormalities of the type observed in trisomic chromosomal disorders were associated with synaptic immaturity. Severe testicular hypogonadism accompanied bilateralmacro-orchidism, normal penis, and unilateral hydrocele. Valvular, articular, and testicular interstitial compartments showed normal histochemical staining characteristics for glycoproteins and lipids.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Aghajanian GK, Bloom FE (1967) The formation of synaptic junctions in developing rat brain: a quantitative electron-microscopic study. Brain Res 6:716–727

    Google Scholar 

  • Allan W, Herndon CN, Dudley FC (1943/1944) Some examples of the inheritance of mental deficiency: apparently sexlinked idiocy and microcephaly. Am J Ment Defic 48:325–334

    Google Scholar 

  • Belonoschkin B (1954) Spermiogenesis in elderly men. Fertil Steril 5:182–192

    Google Scholar 

  • Bickers DS, Adams RD (1949) Hereditary stenosis of the aqueduct of Sylvius as a cause of congenital hydrocephalus. Brain 74:246–262

    Google Scholar 

  • Borjeson M, Forssman H, Lehmann O (1962) An X-linked, recessively inherited syndrome characterized by grave mental deficiency, epilepsy and endocrine disorders. Acta Med Scand 171:13–21

    Google Scholar 

  • Bostrom K, Brun A (1971) Testicular changes in association with malformation of the central nervous system and mental retardation. Acta Pathol Microbiol Scand [A] 79:249–256

    Google Scholar 

  • Bowen P, Bierderman B, Swallow KA (1978) The X-linked syndrome of macro-orchidism and mental retardation: Further observations. Am J Med Genet 2:409–414

    Google Scholar 

  • Brown WT, Mezzacappa PM, Jenkins EC (1981) Screening for fragile X syndrome by testicular size measurement. Lancet II:1055

    Google Scholar 

  • Brown WT, Jenkins EC, Freidman E, Brooks J, Wisniewski K, Raguthu S, French J (1982) Autism is associated with the fragile X syndrome. J Autism Dev Disord 12:303–308

    Google Scholar 

  • Cantu MM, Scaglia HE, Medina M, Gonzalez-Diddi M, Morato T, Moreno ME, Perez-Palacios G (1976) Innerited congenital normofunctional testicular hyperplasia and mental deficiency. Hum Genet 33:23–33

    Google Scholar 

  • Cantu JM, Scaglia HE, Gonzalez-Diddi M, Hernandez-Jauregui P, Morato T, Moreno ME, Giner J, Alcantar A, Herrera D, Perez-Palacios G (1978) Inherited congenital normofunctional testicular hyperplasia and mental deficiency. A corroborative study. Hum Genet 41:331–339

    Google Scholar 

  • DeGroot D, Vrensen G (1978) Postnatal development of synaptic contact zones in the visual cortex of rabbits. Brain Res 147:362–369

    Google Scholar 

  • Deroover J, Fryns JP, Parloir C, Van Den Berghe H (1977) X-linked recessively inherited non-specific mental retardation. Report of a large family. Ann Genet 20:263–268

    Google Scholar 

  • Dunn HG, Renpenning H, Gerrard JW, Miller JR, Tabata T, Federoff S (1963) Mental retardation as a sex-linked defect. Am J Ment Defic 67:827–848

    Google Scholar 

  • Edwards JH (1961) The syndrome of sex-linked hydrocephalus. Arch Dis Child 36–486

  • Fried K (1973) X-linked mental retardation and/or hydrocephalus. Clin Genet 3:258–263

    Google Scholar 

  • Hafez ESE (1976) Reproductive senescence. In: Hafez ESE (ed) Aging and reproductive physiology. Perspecitives in human reproduction, vol 2. Ann Arbor Science, Ann Arbor

    Google Scholar 

  • Huttenlocher PR (1974) Dendritic development in neocortex of children with mental defect and infantile spasms. Neurology 24:203–210

    Google Scholar 

  • Jenkins EC, Brown WT, Brooks J, Duncan CJ, Rudelli RD, Wisniewski HM (1984) Experience with prenatal fragile X detection. Am J Med Genet 17:215–239

    Google Scholar 

  • Klinger HP (1972) Rapid processing primary embryonic tissue for chromosome banding pattern analysis. Cytogenetics 11:424–435

    Google Scholar 

  • Lowenthal A, Bruyn GW (1968) Calcification of the striopallido dentate system. In: Vinken PJ, Bruyn GW (eds) Diseases of the basal ganglia. Handbook of clinical neurology, vol 6. North Holland, Amsterdam, pp 703–725

    Google Scholar 

  • Mancini RE, Lavieri JC, Muller F, Andrada JA, Saraceni DJ (1966) Effect of prednisolone upon normal and pathologic human spermatogenesis. Fertil Steril 17:500–513

    Google Scholar 

  • Marin-Padilla M (1972): Structural organization of the cerebral cortex in human chromosomal aberrations. A Golgi study. Brain Res 44:625–629

    Google Scholar 

  • Marin-Padilla M (1974) Structural organization of the cerebral cortex (motor area) in human chromosomal aberrations. A Golgi study. ID (13–15) trisomy, Patau syndrome. Brain Res 66:375–391

    Google Scholar 

  • Marin-Padilla M (1975) Abnormal neuronal differentiation (functional maturation) in mental retardation. Birth Defects 11:133–153

    Google Scholar 

  • Marin-Padilla M (1976) Pyramidal cell abnormalities in the motor cortex of child with Down's syndrome. A Golgi study. J Comp Neurol 167:63–82

    Google Scholar 

  • Menkes JH, Phillippart M, Clark DB (1964) Hereditary partial agenesis of corpus callosum. Arch Neurol 11:198–208

    Google Scholar 

  • Nielsen KG (1983) Diagnosis of the fragile X syndrome (Martin-Bell syndrome). Clinical findings in 27 males with fragile site at Xq28. J Ment Defic Res 27:211–226

    Google Scholar 

  • Opitz JM, Sutherland GR (1984) Conference report: International workshop on the fragile X and X-linked mental retardation. Am J Med Genet 17:5–94

    Google Scholar 

  • Oshima H, Nankin HR, Troen P, Yoshida K, Ochi-Ai K (1977) Leydig cell number and function in infertile men. In: Troen P, Nankin HR (eds) The testis in normal and infertile men. Raven Press, New York, pp 445–455

    Google Scholar 

  • Purpura DP (1974) Dendritic spine “dysgenesis” and mental retardation. Science 186:1126–1128

    Google Scholar 

  • Rai KR, Sawitsky A, Cronkite EP, Chanana AD, Levy RN, Pasternak CK (1975) Clinical staging of chronic lymphocytic leukemia. Blood 46:219–234

    Google Scholar 

  • Renpenning H, Ferrard JW, Zaleski WA, Tabata T (1962) Familial sex-linked mental retardation. Can Med Assoc J 87:954–956

    Google Scholar 

  • Rhoads FA (1982) X-linked mental retardation and fragile X or marker X syndrome. Pediatrics 69:668–669

    Google Scholar 

  • Rudelli RD, Jenkins EC, Wisniewski K, Moretz R, Byrne J, Brown WT, (1983) Testicular size in fetal fragile X syndrome. Lancet I:1221–1222

    Google Scholar 

  • Ruvalcaba RHA, Myhre SA, Roosen-Runge EC, Beckwith JB (1977) X-linked mental deficiency. Megalotestes syndrome. JAMA 238:1646–1650

    Google Scholar 

  • Sargent JW, McDonald JR (1948) A method for the quantitative estimate of Leydig cells in the human testis. Proc Staff Meet Mayo Clin 23:249–254

    Google Scholar 

  • Scheibel AB (1979) Aging in human motor control systems. In: Ordy JM, Brizzees K (eds) Sensory systems and communication in the elderly, vol 10: Aging. Raven Press, New York, pp 297–310

    Google Scholar 

  • Scheibel ME, Tomiyasu U, Scheibel AB (1977) The aging human Betz cell. Exp Neurol 56:598–609

    Google Scholar 

  • Scott BS, Becker LE, Petit TL (1983) Neurobiology of Down's syndrome. Prog Neurobiol 21:199–237

    Google Scholar 

  • Smith RD, Fineman RM, Myers GG (1980) Short stature, psychomotor retardation, and unusual facial appearance in two brothers. Am J Med Genet 7:5–9

    Google Scholar 

  • Sovik O, Van Der Hagen CB, Loken AC (1977) X-linked aqueductal stenosis. Clin Genet 11:416

    Google Scholar 

  • Suetsugu M, Mahraein P (1980) Spine distribution along the apical dendrites of the pyramidal neurons in Down syndrome. A quantitative Golgi study. Acta Neuropathol (Berl) 50:207–210

    Google Scholar 

  • Sutherland GR (1977) Fragile sites on human chromosomes: Demonstration of their dependence on the type of tissue culture medium. Science 197:265–266

    Google Scholar 

  • Sylvester PE (1973) The testes in the mentally handicapped. J Ment Defic Res 17:52–57

    Google Scholar 

  • Takashima S, Becker LE, Armstrong DL, Chan FW (1981) Abnormal neuronal development in the visual cortex of the human fetus and infant with Down's syndrome. A quantitative and qualitative Golgi study. Brain Res 225:1–21

    Google Scholar 

  • Turner G, Jacobs P (1983) Marker (X)-linked mental retardation. Adv Hum Genet 13:83–112

    Google Scholar 

  • Turner G, Eastman E, Casey J, Mcleay A, Procopis P, Turner B (1975) X-linked mental retardation associated with macroorchidism. J Med Genet 21:367–371

    Google Scholar 

  • Williams RS, Hauser SL, Purpura DP, DeLong GR, Swisher CN (1980) Neuropathologic studies performed in four retarded persons with autistic behavior. Autism and Mental Retardation. Arch Neurol 37:749–753

    Google Scholar 

  • Wisniewski K, French J, Fernando S, Brown WT, Jenkins EC, Friedman E, Hill AL, Miezejeski CM (1985) Fragile X syndrome. Associated neurological abnormalities and developmental disabilities. Annals Neurol (in press)

  • Wong TW, Strauss FH, Worne NE (1973) Testicular biopsy in the study of male infertility. I. Testicular causes of infertility. Arch Pathol Lab Med 95:151–159

    Google Scholar 

  • Zachman M, Prader A, Kind HP, Baflinger H, Budlinger H (1974) Testicular volume during adolescence. Helv Paediatr Acta 29:61–72

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rudelli, R.D., Brown, W.T., Wisniewski, K. et al. Adult fragile X syndrome. Acta Neuropathol 67, 289–295 (1985). https://doi.org/10.1007/BF00687814

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00687814

Key words

Navigation