Neurology India
menu-bar5 Open access journal indexed with Index Medicus
  Users online: 11276  
 Home | Login 
About Editorial board Articlesmenu-bullet NSI Publicationsmenu-bullet Search Instructions Online Submission Subscribe Videos Etcetera Contact
  Navigate Here 
  » Next article
  » Previous article 
  » Table of Contents
 Resource Links
  »  Similar in PUBMED
 »  Search Pubmed for
 »  Search in Google Scholar for
 »Related articles
  »  Article in PDF (90 KB)
  »  Citation Manager
  »  Access Statistics
  »  Reader Comments
  »  Email Alert *
  »  Add to My List *
* Registration required (free)  

  In this Article
 »  Abstract
 »  Introduction
 »  Case Report
 »  Discussion
 »  Acknowledgements
 »  References

 Article Access Statistics
    PDF Downloaded153    
    Comments [Add]    
    Cited by others 5    

Recommend this journal

Year : 2004  |  Volume : 52  |  Issue : 1  |  Page : 104-105

Association of schizophrenia and mental retardation with facio-scapulohumeral muscular dystrophy

Department of Neurology, MMI Hospital, Lalpur, Raipur (C.G.) - 492007

Correspondence Address:
Department of Neurology, MMI Hospital, Lalpur, Raipur (C.G.) - 492007
[email protected]

  »  Abstract

Three members of an Indian family with facio scapulohumeral dystrophy (FSHD linked to chromosome 4q35 with short EcoR1 segment of 23 Kb are reported where two male adults had schizophrenia. One family member developed isolated facial weakness with mild mental retardation. This genetically proven FSHD family is reported because of its uncommon associations.

How to cite this article:
Sharma S, Namrata S. Association of schizophrenia and mental retardation with facio-scapulohumeral muscular dystrophy. Neurol India 2004;52:104-5

How to cite this URL:
Sharma S, Namrata S. Association of schizophrenia and mental retardation with facio-scapulohumeral muscular dystrophy. Neurol India [serial online] 2004 [cited 2021 Dec 8];52:104-5. Available from:

  »   Introduction Top

Facio scapulohumeral dystrophy (FSHD) is an autosomal dominant muscle disease, usually presenting before the age of 20 years. FSHD results from a deletion of integral copies of a 3.3 Kb DNA repeat motif named D4Z4 on chromosome 4.[1],[2]
Association of schizophrenia with FSHD is unknown. The current hypothesis for causation of schizophrenia involves multiple genes with mild to moderate effect and non-genetic risk factors.[3] The mental retardation is a described feature of childhood FSHD with larger deletion defect.[4],[5] An Indian FSHD family is reported where two male adults had schizophrenia and one additional family member had isolated facial weakness and mild mental retardation. FSHD has been linked to 4q35 with short EcoR1 segment of 23 Kb in these three patients. It is suggested that schizophrenia may be an association of FSHD.

  »   Case Report Top

The family pedigree [Figure - 1] based on information available of 17 family members in three generations indicates that the pattern of inheritance is autosomal dominant. Family members with FSHD were evaluated in detail and DNA studies were performed.
The mother in the described family (II-2), a 58-year-old woman developed muscle disease at the age of 8 years. She had advanced disease-involving face with inability to close eyes, hollowed cheeks with persistent pouting, markedly wasted shoulder girdle and brachial muscles, abdominal muscle weakness and exaggerated lumbar lordosis. The deep tendon reflexes were absent. She was self-dependent for activities of daily living.
All her three sons developed FSHD. The disease was confined to wasting and weakness of face, shoulder girdle and upper extremities. The deltoid and forearm muscle mass was relatively preserved. The deep tendon reflexes were absent in the upper limbs. The elder two of them became schizophrenic in addition at the age of 30 and 15 years. The estimation of serum CPK done in all the cases was near the normal range. The needle EMG revealed a myopathic pattern with reduced duration and amplitude of the motor potential, increased polyphasic potential, more marked in the brachial biceps. The muscle biopsy done in two patients showed marked variation in fiber size, some of the fibers were small atrophic, while some were large hypertrophied. There were foci of interstitial mononuclear infiltrates, consistent with the diagnosis of FSHD. The Southern blotting analysis performed using p13 E-11 probe in family members confirmed 4q35-linked FSHD. All three patients had short EcoR1 fragment of 26 Kb that became shortened to 23 Kb by EcoR1/B1n1 double digestion.
One other family member (III-3) had facial weakness without shoulder girdle and upper limb involvement. She also had mild mental retardation with IQ of 75. The DNA analysis revealed an EcoR1 fragment of the same size [Table - 1]

  »   Discussion Top

FSHD is characterized by progressive weakness of the muscles of the face, upper arms and shoulder girdle. Early onset FSHD is often associated with retinal telangiectasia and sensorineural deafness.[6]
Genetic linkage has mapped the FSHD gene to the subtelomeric region of chromosome 4q35. Detection is done by Southern blot analysis of DNA using the p13E-11 probe. An ECOR1 fragment less than 38 Kb is associated with FSHD. The shorter fragment length produces more severe and early manifestation of the disease.[7],[8] Recently, six sporadic cases with atypical presentation like facial-sparing disease and lower limb involvement at the onset have been described and confirmed on DNA testing, however parental genetic tests have not been performed.[9] The present FSHD family had short EcoR1 segment of 23 Kb. To the best of our knowledge this is first Indian family reported with genetic studies.
Early onset FSHD with severe mental retardation and epilepsy has been described from Japan.[4] Funakoshi et al (1990) reported a high frequency of both mental retardation and epilepsy with smallest ECOR1 fragment of 10-11 Kb. One of our family members had mild mental retardation and isolated facial weakness with ECOR1 fragment of 23 Kb.
A number of specific genes like the 5 - hydroxytryptamine type 2-a receptor gene, dopamine D3 receptor gene localized to multiple chromosomes including 6p, 6q, 8p, 13q and 22q are suggested to be involved in the causation of schizophrenia.[3] It is not a described feature of FSHD. Zatz et al reported a family in which four of five adult patients with Becker muscular dystrophy had schizophrenia or related spectrum. They postulated the possible locus for schizophrenia on XP-21 or a possibility of an abnormal expression of the dystrophy gene itself. This case report suggests that FSHD can have uncommon central nervous system involvement and should be specifically evaluated in Indian FSHD families.

  »   Acknowledgements Top

The authors wish to thank Yukiko K.Hayashi, M.D, Kanako Goto, Department of Neuromuscular Research, National Institute of Neuroscience, NCNP, Kodaira, Tokyo, Japan for performing the Southern blot analysis of our patients. 

  »   References Top

1.Wijmenga C, Frants RR, Brouwer OF, et al. Location of facioscapulohumeral muscular dystrophy gene on chromosome 4. Lancet 1990;336:651-3.   Back to cited text no. 1  [PUBMED]  
2.Lyle R, Wright TJ, Clark LN, et al. The FSHD-associated repeat, D4Z4, is a member of a dispersed family of homeobox-containing repeats, subsets of which are clustered on the short arm of the acrocentric Chromosomes. Genomics 1995;28:389-97.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]
3.Mowry BJ, Nancarrow DJ. Molecular genetics of schizophrenia.Clin Exp Pharmacol Physiol 2001:28:66-9.  Back to cited text no. 3    
4.Miura K, Kumagai T, Matsumoto A, Iriyama E, Watanabe K, Goto K, et al. Two cases of chromosomes 4q35 - linked early onset facioscapulohumeral dystrophy with mental retardation and epilepsy. Neuropediatrics 1998;29:239-41.   Back to cited text no. 4  [PUBMED]  
5.Funakoshi M, Goto K, Arahata K. Epilepsy and mental retardation in a subset of early onset 4q35 facioscapulohumeral muscular dystrophy. Neurology 1998;50:1791-4.  Back to cited text no. 5  [PUBMED]  
6.Brouwer OF, Padberg GW, Bakker E, Wijmenga C, Frants RR. Early onset facioscapulohumeral muscular dystrophy. Muscle Nerve 1995;2:S67-72.  Back to cited text no. 6    
7.Tawil R, Figlewicz DA, Griggs RC, et al. Facioscapulohumeral Dystrophy: a distinct regional myopathy with a novel molecular pathogenesis. Ann Neurol 1996;43:279-82.  Back to cited text no. 7    
8.Tawil R, Forrester J, Griggs RC, et al. Evidence for anticipation and association of deletion size with severity in FSH muscular dystrophy. Ann Neurol 1996;39:744-8.  Back to cited text no. 8  [PUBMED]  
9.Van der Kooi Aj,Visser Mc, Rosenberg N, Van den Berg-Vos R, et al. Extension of the clinical range of facioscapulohumeral dystrophy: report of six cases. JNNP 2000;69:114-6.  Back to cited text no. 9    


Print this article  Email this article
Previous article Next article
Online since 20th March '04
Published by Wolters Kluwer - Medknow