Clin Genet 2000: 57: 456–458Printed in Ireland. All rights reser6ed

Letter to the Editor

The comparison of anthropometric variablesin mentally retarded boys with and withoutfragile X syndrome

To the Editor:The fragile X syndrome is one of the most frequenthereditary forms of mental retardation, and has anestimated incidence of one in 4000 males (1).

The main characteristics of fragile X males arethe moderate degree of mental retardation,macroorchidism and peculiar facial appearance,including elongated narrow face with large, some-times protruding ears, and prominent jaw. Thesefacial features tend to be more noticeable in adultsthan in children (2). Though large and prominentears are common features in both adults and chil-dren, the use of clinical criteria only to recognizethe fragile X syndrome can often be difficult.Sometimes young fragile X children appear quitenormal looking, whereas some characteristicfragile X features are observed also in non-fragileX mentally retarded boys. As a consequence, manyindividuals remain undiagnosed.

Apart from the visible features characteristic forfragile X syndrome, the anthropometric measure-ments were taken into consideration for the pre-liminary recognition of the etiology of mentalretardation. However, almost all of these studieswere confined to adult males (3, 4), with a smallnumber of children (5–7). Moreover, these chil-dren were included in the general group and theirdata were estimated together with those obtainedfrom adults.

In order to enlarge the number of variablesuseful in the preliminary evaluation of mental re-tardation, an analysis of anthropometric variablesin mentally retarded boys with and without thefragile X syndrome, but with features of fragile Xsyndrome, was undertaken.

Forty-two mentally retarded boys with the char-acteristic features of fragile X syndrome apparentby visual inspection, such as large and often pro-truding ears, as well as elongated face, werestudied.

Cytogenetic and molecular analyses indicatedthat only in 16 boys examined were fragile sitesand methylated full mutations found, whereas in

26 of them no recognizable cause of retardationwas detected. The average age of fragile X boyswas 10.74 years, with a range of 5–17. Their aver-age IQ was 47, with a range of 22–68. The averagefra(X) frequency in lymphocytes cultured in TC199 medium was 6%, with a range of 0–17%,whereas in cultures with MTX added, this fre-quency increased to 12.20%, with a range of 1–30%. The number of CGG repeats in the first exonof the FMR 1 gene ranged from 250 to 1300. Theboys with no fragile site and with CGG repeatsbelow 60 were described as the non-fragile Xgroup. Their average age was 10.35 years, with arange of 5–17. Their average IQ was 49, with arange of 26–71.

Physical examinations and anthropometric mea-surements were made by one person according tothe instructions and with a set of measuring instru-ments manufactured by Martin and Saller (8). Themeasured variables included height, weight, upperextremity length (a-da III), lower extremity length(B-sy), hand length (sty-da III), head width (mr-mu), head length (g-op), hand breadth (eu-eu),head breadth, total face height (n-gn), bizygomaticdiameter (zy-zy), bigonial diameter (go-go), noseheight (n-sn), nose width (al-al), ear height (sa-aba), ear width (pa-pra) and inner canthal distance(en-en). In addition, the seven following indexeswere calculated: cephalic, total face, mandibular-zygomatic, ear, nose, upper extremity length tostature and lower extremity length to stature. Nor-mative values for Polish children were obtainedfrom published papers (9–11). Testicular volumewas not measured because of the lack of normativevalues for children.

Z scores were computed using normative mea-surements to control age and sex, and were calcu-lated from the formula Z= (y−x)/SD, where SDis the standard deviation of normal control indi-viduals, x is the average of normal control individ-uals, and y is the measurement of the subject.Further, t-tests were undertaken on the Z scores todetermine if significant anthropometric differencesexist between fragile X and non-fragile X boys.

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Table 1. Z score data (average9SD) for anthropometric variables formentally retarded males with and without fragile X syndrome

Fragile X group Non-fragile X groupVariable

−0.291.00* −0.9791.16HeightWeight 0.6691.91** −0.7991.07

−0.6191.19Upper limb length −0.2991.06−0.9591.10Lower limb length −0.9290.93

Hand length −1.5491.69 −1.7891.51−0.7690.79 −1.5691.19Hand width−0.1291.19Head length −0.4491.29

Head width 0.2791.13* −0.4691.26Total face height 0.4491.02 −0.1991.25

0.4890.77Bizygomatic diameter −0.6191.57Bigonial diameter −0.5890.84 −0.7191.02

−0.4690.47 −0.6390.86Nose height0.8290.86Nose width 0.819098

Ear height 0.9591.17 0.591.46Ear width 2.3891.24** 0.1891.22

0.3691.41Inner canthal distance 0.0191.24Lower limb index −0.1791.41* 0.491.14Upper limb index −0.3590.85 0.1590.57

0.1690.79Total face index −0.4491.23−0.1391.32Jaw index −0.791.51

0.6390.85Nose index 0.6691.03Ear index 1.1391.30* −0.4691.59

0.3791.09* −0.491.16Cephalic index

* pB0.05.** pB0.001.

X boys, the Prader–Willi syndrome had been ini-tially suspected. On the contrary, the weight valuesreported by Partington (7) for fragile X boys weresimilar to published standards. The comparison ofretarded males with and without fragile X syn-drome reported by Butler (5, 6) also showed nodifference between their weights, even when youngboys were included. However, our results supportthe observations of Schrander-Stumpel et al. (13),and despite the differences described above seem toindicate that the fragile X syndrome should beincluded in the differential diagnosis of mentallyretarded obese boys. A significantly increased earwidth was noted in the majority of fragile X boyswhen compared with non-fragile X ones, thusconfirming the results of previous studies in boysand adults (5, 6).

Our study shows that a detailed physical exami-nation and anthropometric measurements in men-tally retarded boys, with special attention given toheight and weight, as well as to ear, head and faceparameters, may be very helpful to increase diag-nostic efficiency.

However, further research is needed to confirmthese results in a larger sample of mentally re-tarded boys with and without fragile syndrome.

Małgorzata LisikKrystyna Szymanska-Parkieta

Urszula Gałecka

AcknowledgementsWe thank the families who participated in this study fortheir cooperation. We also thank T. Mazurczak, J. Bal andM. Milewski from the Department of Genetics, NationalResearch Institute of Mother and Child in Warsaw forsupport in molecular analysis and kind suggestions.

References

1. Turner G, Webb T, Wake S, Robinson H. Prevalence offragile X syndrome. Am J Med Genet 1996: 64: 196–197.

2. Nussbaum RJ, Ledbetter A. The fragile X syndrome. In:Scriver CR, Beaudet AL, Sly W, Valle D, Stanbury JB,eds. The Metabolic and Molecular Bases of Inherited Dis-eases. New York: McGraw-Hill, 1995: 795–806.

3. Loesch DZ, Lafranchi M, Scott D. Anthropometry inMartin–Bell syndrome. Am J Med Genet 1988: 30: 149–164.

4. Meryash DL, Cronk CE, Sachs B, Park SG. An anthropo-metric study of males with the fragile X syndrome. Am JMed Genet 1984: 17: 159–174.

5. Butler MG, Alen GA, Haynes JL, Singh DN, Watson MJ,Breg WR. Anthropometric comparision of mentally re-tarded males with and without the fragile X syndrome. AmJ Med Genet 1991: 38: 260–268.

6. Butler MG, Pratesi R, Breg WR, Singh DN. Anthropo-metric and craniofacial patterns in mentally retarded maleswith emphasis on the fragile X syndrome. Clin Genet 1993:44: 129–138.

A visual inspection of all investigated boysshowed that they had the appearance characteristicof the fragile X syndrome, yet only in 38% of themwas the fragile X syndrome detected. The compari-son of physical examination and anthropometricvariables of mentally retarded boys with and with-out the fragile X syndrome showed that there weredifferences between them. The comparisons be-tween average values of age adjusted anthropomet-ric measurements in the form of Z scores on allfragile X and non-fragile X boys are summarizedin Table 1. There was significantly increased earwidth compared with standards (mean Z score\2)in the fragile X boys. Significant differences (pB0.05) were found between fragile X and non-fragileX boys with respect to three measurements, suchas height, head width, total face height and to theindexes of cephalic, ear and lower extremity lengthto stature. The greatest differences (pB0.001) werefound in ear width and weight. There were nosignificant differences between these two groups inother analyzed anthropometric variables.

Significantly low weight may suggest anothercause of mental retardation other than fragile Xsyndrome. The weight of the investigated fragile Xboys was significantly higher than that in non-fragile X boys, with a quarter of them having Zscore \2 SD, and also than that in healthy boyspreviously compared (12). Moreover, in two fragile

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7. Partington MW. The fragile X syndrome II: preliminarydata on growth and development in males. Am J MedGenet 1984: 17: 175–194.

8. Martin R, Saller K. Lehrbuch der anthropologie. Stutt-gart: Gustav Verlag, 1957: 308–386.

9. Cieslik J, Kaczmarek M, Kaliszewska-Drozdowska M.Dziecko poznanskie. Bogucki Wydawnictwo NaukowePoznan 1994: 90: 15–109.

10. Niedzwiecka Z. Rozwoj fizyczny dzieci warszawskich zdobrych warunkow srodowiskowo-bytowych. Badaniadlugoterminowe. Wychowanie Fizyczne i Sport 1986: 3:39–57.

11. Szczotkowa Z. Badania morfologii malzowiny usznej. Ma-terialy i Prace Antropometryczne 1977: 93: 51–86.

12. Lisik M, Szymanska-Parkieta K, Galecka U. Selected

body and head proportions in children with fragile Xsyndrome. Pediatria Polska 1998: 73: 291–296.

13. Schrander-Stumpel C, Gerver WJ, Meyer H, Engelen J,Mulder H, Fryns JP. Prader–Willi-like phenotype infragile X syndrome. Clin Genet 1994: 45: 175–180.

Correspondence:Malgorzata LisikDepartment of Medical GeneticsSilesian University School of Medicine18 Medykow Str40752 KatowicePolandTel/fax: +4832 2046151E-mail: biblig@informed.slam.katowice.pl

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