J. ment. Defc. Res. (1981) 25, 253 253

FRAGILE X-LINKED MENTAL RETARDATION:THE MARTIN-BELL SYNDROME

B. \V. RICHARDS, P. E. SYLVESTER and CAROL BROOKERSt Lawrence^s Hospital, Caterkam, Surrey, CR3 5YA

INTRODUCTIONIn 1943 Martin and Bell reported a family in which eleven mentally retarded

sons were born to mothers of normal intelligence, the degree of mental retardationbeing severe in all of them. The authors observed that "In spite of certain difficulties,it is believed that the mental defect is due to a sex-linked recessive gene". Twofemales displayed "slight mental deficiency" and the authors comidered that in thesetwo the causal gene was incompletely recessive. The mode of transmission is unusualand of particular interest in this family in so far as all affected subjects are derivedfrom three sibs, namely two normal lirothers and their normal sister. The normalsister had two affected sons. All other affected sons had normal mothers who werethe daughters of the two normal brothers. This is showr on the original pedigree ofMartin and Bell reproduced here (Fig. 1). The authors suggested that some con-trolling factor caused suppression of the disease in the normal brothers withoutaffecting their liability to transmit it.

Marlin and Bell found no characteristic symptoms in affected subjects althoughI hey referred to dispropoi tionalely severe disability in respect of speech. They statedthat sex development was normal, the ages of the nine cases examined ranging fromseventeen to thirty-seven years at the lime.

Two brothers belonging to this famil>' have been resident at St Lawrence'sHospital for many years (V50, V51) and a cousin was admitted later (V54). Bio-chemical and chromosomal investigations many years ago yielded normal results.

Table 1

Blood samples examined for fraX chromosome after culture in folatt deficient media

Mo. of cells Percentagetvithout with withfraX fraX No. of cells constriction

Case No. Source ' (G-banding) examined %

37 3528 4ti40 50

18 17

30 nil

{Received 7th October, 1981)

V50V5IV54V4IV16V18V19IV22

St Lawrence sSi Lawrence'sSt Lawrence'sBotleys ParkLeavesdenLeavesdenLeavesdenMother of V54

241.̂20

many15culturecuhurc

30

131320

13

failedfailed

nil

254 FRAGILE X

Fig. 2. X-chromosome showing fragilesite (fra(X)(q27)) (Case V54).

Fi^. 3. Brothers at St Lawrence's (a) case V50 aged 69. Note large ears, helixinadequately formed; antihelix also incomplete so thai antihelix and concha arefused, forming a large funnel arrangement, (b) Case V5I aged 66. Note large

ears, especially lobes.

Fig. 1. (•run,ill.I ul \ 30 with results ofmeasurement of testes.

Fig. 5. Case V54 aged 56.

B. W. RICHARDS et al. 255

Fig. 6. Case V41 aged 67. Fig. 8. Case VIS aged 7L

l-ig, 7. Clase V19 aged 69.Fig. 9. Case V16 aged 75.

Following reports of the terminal X constriction in mentally retarded subjects,and of characteristic symptoms (Lubs, 1969; Harvey, Judge and Wiener, 1977), wehave re-examined these cases. We also examined another four members of this familyknown to us, three at Leavesden Hospital (V16, V18, VI9) and one at Botleys ParkHospital (V41), seven cases in all.

The results of examining chromosomes using folic acid deficient media (Suther-land. 1979) are shown in Table 1 and Fig. 2. The fragile X with terminal X constric-tion was identified in five of seven cases. Tbe other two cultures failed.

The facial appearance of some, but not all, affected subjects is as described byoilier aiitliors, with piognathism and large cars (Figs. 3-9). Four of them have macro-orchidism according to our measurements. All arc severely retarded and two onlyhave sufficient speech for limited conversation to be possible.

The purpose of this communication is to record that the family reported byMartin and Bell in 1943, the first known example of X-linked mental retardation,is associated with a terminal X-constriction. We propose the term "Martin-Bellsyndrome" for X-iinked mental retardation associated with terminal X-chromosome

256 • FRAGILE Xr

constriction. This excludes normal males who display the X-constrictioii {Uaker,Chidioc, Fear and Berry, 1981). As observed by The Lancet (1981), the populationfrecjtiency of this anomaly is as yet unknown and otherwise normal males with it maynot he rare.

"Macro-orchidism-Marker X (MOMX)", suggested by Turner and Opiiz(1980), includes no reference to mental retardation and macro-orchidism is notpresent in all cases, Abl)reviaiions should lie avoided where possible and "MOMX"has a rather unpleasant ring.

We hope that the term "Maitin-Bell syndrome" will be adopted as standardpractice, not only injustice to the authors but also because, in our limited state ofknowledge, it makes no unwarranted assumptions.

ACKNOWLEDGEMENTSWe thank DrC. I. Finnof Leavesden hospital and Drs H. Hamilton-Hislopand H.

Kinncll of Botleys Park hospital for enabling me to examine and investigate membersofthe family resident at iheir respective institutions.

SUMMARYSeven members ofthe original family of sex-Hnked mental retardation reported

by Martin and Bell in 1943 have been re-examined and five of them proved to carry afragile X chromosome. Some also display the typical facial appearance associatedwith this anomaly, and some have macro-orchidism. It is proposed that the conditionshould be designated "The Martin-Bell syudrome".

REFERENCESDAKER, M . G. , CUIDIOC, P., FEAR, C . N . and BERRY, A. C. (1981) Fragile X in a normal

male: A Cautionary Tale. Lancet, ii, 780.HARVEY, J., JUDGE, C . and WIENER, S, (1977) Familial X-linked mental retardation wilh an

X chromosome abiioi mallty. J. med. Genet. 14, 46.LANCET (1981) X-linkcd mental retardation. Leading Article, t, 10B6.LuBS, H. A. (1969) A marker X chromosome. Amer. J. Hum. Genet. 21, 231.MARTIN, J. P. and BKLL, Julia (1943) A pedigree of mental deleet showing sex-linkage. J.

Neurol. VI (New series, li & 4) 154.SuTHERi..\NU, Ci. R. (1979) Heritable fragile sites ofhuman chromosomes: L Factois affecting

expression in lymphocyte culture. Amer. J. Hum. Genet. 31, 125.TURNER, G . and OPITZ, J. M. (1980) X-linkcd mental retardation. Amer.J. med. Genet. 7, 407.

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