Gross
and Fine Motor
Development
in 45,X
and
47,XXX
Girls
James
A. Salbenblatt,
MD, Deborah
C. Meyers,
RPT, MS,
Bruce G. Bender,
PhD, Mary G. Linden,
MS, and Arthur
Robinson,
MD
From the National Jewish Center for Immunology and Respiratory Medicine and the University of Colorado School of Medicine, Denver
ABSTRACT. Neuromuscular deficits have been described in 47,XXY and 47,XYY boys, but gross and fine motor development of girls with sex chromosome aneuploidy has not been extensively studied. Twenty-one propositae, 8 to 19 years of age, identified through newborn screening
to be 45,X, 47,XXX, or 45,X mosaic, and 11 control girls were evaluated by a physical therapist unaware of their genetic constitution. The Bruininks-Oseretsky Test of
Motor Proficiency (BOTMP) was administered, and the
quality of neuromuscular function was determined. The
45,X and 47,XXX propositae exhibited both gross and
fine motor dysfunction, with 12 of 15 BOTMP composite scores below the 10th percentile. The clinical assessment confirmed the BOTMP findings, with 13 propositae ex-hibiting dysfunctional sensory-motor integration. A delay in the age of independent walking confirmed the consist-ency of motor developmental dysfunction throughout time. Sex chromosome mosaics were more similar to control girls. The gross and fine motor delays were fre-quently associated with a moderate to severe language dysfunction which adversely affected classroom perform-ance. Regular developmental assessments of children with sex chromosome aneuploidy, including sensory-mo-tor integration, should assist in the identification of early developmental delays and permit appropriate interven-tion. Pediatrics 1989;84:678-682; sex chromosome, motor
development.
type. The availability of these data will enable
parents to anticipate the therapeutic and
educa-tional needs of their children.
The longitudinal evaluation of persons with sex
chromosome aneuploidy, identified by newborn screening, has provided an opportunity to prospec-tively observe their development during a 24-year period in the Denver Family Development Study.2’3 The cognitive,2 speech-language,4 and learning disability5 status of these persons have been
docu-mented. The gross and fine motor development of
the boys revealed a mild to moderate dysfunctional
sensory-motor integration which adversely affected
school performance.6 The visual-spatial deficit in Turner syndrome has been well studied,7 although
the gross and fine motor development of 45,X and
47,XXX girls has not been reported. Therefore, the
purpose of this study was to describe the
neuro-muscular status and sensory-motor integration of
sex chromosome aneuploid girls, unselected for
phenotype, to increase our understanding of the
effect of sex chromosome aneuploidy on
neuromus-cular development and its possible association with learning problems.
Sex chromosome aneuploidy is a common
chro-mosomal abnormality, occurring in approximately 2 per 1000 female newborns.’ More of these individ-uals are identified because of the increased availa-bility of amniocentesis and chromosome analysis,
resulting in a need for information regarding the
clinical findings of subjects unselected for
pheno-Received for publication Oct 24, 1988; accepted Dec 20, 1988. Reprint requests to (AR.) National Jewish Center for Immu-nology and Respiratory Medicine, 1400 Jackson St, Denver, CO 80206.
PEDIATRICS (ISSN 0031 4005). Copyright © 1989 by the American Academy of Pediatrics.
MATERIALS
AND METHODSThe 21 propositae were identified through X
chromatin examination of the amniotic membranes
obtained from placentas of 40 000 consecutive
new-borns at two Denver hospitals, and all were
con-firmed by karyotype analysis. Individuals available
for this motor study included five 45,X (8 to 16
years of age), ten 47,XXX (10 to 19 years of age),
and two partially monosomic X chromosome
var-iants and four sex chromosome mosaics without
morphologically abnormal X chromosomes (9 to 18
years of age). Seven X chromatin-positive sisters of
propositae and four additional eukaryotic female
Den-ARTICLES 679
ver Family Development Study were available as a
control group (8 to 18 years of age), with no more
than one girl from any family. Informed consent
was obtained from the parents.
The Bruininks-Oseretsky Test of Motor
Profi-ciency
(BOTMP)8
was administered to each girl bya physical therapist who was unaware of the
kary-otype of the subjects. Propositae and control chil-then were presented for evaluation in random order. The complete BOTMP battery consists of eight subtests of motor proficiency and three composite scores. The test results were compared to the age-and sex-differentiated subtest and composite stand-ard score norms of the standardization sample. The individual girl’s battery composite results are
pre-sented as a percentile, and group subtest and
com-posite
standard
scores
are used for a more detailedcomparison. Older subjects were compared to the
14-year test norms.
In addition to the standardized test, the examiner clinically rated the quality of neuromuscular func-tion in the areas of neurologic status, gross and fine
motor development, and perceptual integration.
This clinically derived framework included 16
ob-servations of nonlocalizing or soft neurologic signs and sensory-motor integration: neurologic status-muscle tone, primitive reflex retention, sensory-motor integration; gross motor development-joint stability, muscle strength, coordination, balance, gait, eye-hand coordination, eye-foot coordination;
fine motor development-bilateral coordination,
eye-hand coordination, prehension/manipulation,
writing; perceptual development-visual
percep-tion, visual-motor integration. These were rated on a 5-point scale developed for this study: 5 =
adap-tive skills within average range, 4 = one area of
weakness and/or soft neurologic sign, 3 = multiple
signs of sensory-motor dysfunction and/or
devel-opmental delays, 2 = developmental deficits
sec-ondary to neurologic interference, and 1 =
signifi-cant neurologic impairment. The 16 ratings were
summed with a maximum score of 80 and a
mini-mum of 16. This total is referred to as the Neuro-logic/Sensory-Motor Integration score.
The age of independent walking was available for
all aneuploid girls but was not documented for the
control girls. Therefore, the age of independent
walking was compared to published norms for the
Denver Developmental Screening Test.9
A psychologist administered the original or
re-vised edition of the Wechsler Intelligence Scale for
Children to provide a comparison of the general
intellectual skills of all groups, and a speech
lan-guage pathologist administered five language tests
to sample receptive language, expressive language, and auditory-memory skills. Historical information
in the record documented educational special serv-ices intervention.
RESULTS
45,X
Four of the five nonmosaic 45,X girls performed
markedly below average limits on the BOTMP with
a battery composite score below the first percentile (Table 1). All three composite standard scores were significantly less than were those of the control girls, as were half of their subtests (Table 2). Except for subject 4, they experienced difficulty with most
of the clinical observations. Neurologically, they
had hypotonia, retention of primitive asymmetric
and symmetric tonic neck reflexes, and
dysfunc-tional sensory-motor integration. The clinical
Neu-rologic/Sensory-Motor Integration scores are also
presented in Table 1. Subject 1 received the lowest cumulative score of 37 and was the only girl to receive ratings of 1 on the 5-point scale, indicating significant neurologic impairment. In contrast, sub-ject 4 did relatively well with evidence of good
sensory-motor integration and normal muscle tone
which was consistent with her strong cognitive and
language skills and absence ofeducational interven-tion. It was also noted that she had fewer physical stigmata than the other members of this group, including a lack of short stature, although she is
short compared with other members of her family.
The others had classic stigmata of Turner
syn-drome.
The developmental status of two girls with
par-tially monosomic X chromosome variants are
pre-sented in Table 1, although the information was
not included in the group comparisons. Subject 6,
with a terminal deletion of the long arm of the X
chromosome, 46,X,del(X)(pter-q21.2:), had
rela-tively short stature and secondary amenorrhea. Her motor skills were excellent in early childhood, and she continued to demonstrate evidence of good sensory-motor integration. She received the highest battery composite percentile of 99 on the BOTMP
and did well on the clinical assessment. Subject 7,
with 45,X/46,X,r(X), did better clinically in
con-trast to her standardized battery composite
per-centile of 1. Early motor problems were recognized,
and she was observed to have some weaknesses in
sensory-motor integration. Physically, she had
short
stature and no evidence of spontaneous pu-berty.Four propositae with sex chromosome mosaicism
were followed up. Subjects 8 through 11 had
BOTMP composite percentiles from 8 to 72 (Table
1). Their three composite standard scores and all
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Karyotype and Walked Late BOTMP Battery Neurologic/Sensory Sensory-Motor Full-Scale Language School
Subject No. after 15 mos. Composite
Percentile
Motor Integration Score
Integration Dysfunction
IQ Dysfunction Intervention
45,X
0 99 74 0
0
59
72
0
0
77
38
0
0
74
8
0
0
68
31
0
0
55
0
129
1 + <1 37 + 50 + FT
2 0 <1 43 + 99 + PT
3
+ <1 43 + 72 + FT4 + 24 75 0 118 0 0
5 0 <1 46 + 73 + PT
Mean (SD) 5.6 (10.3) 48.8 (15.0) 82.4 (26.4)
46,X,del(X) 92 0 0
(pter’-*q21.2:) 6
45,X/46,X,r(X) + 1 84 0 PT
[35:65]
7
45,X/46,XX 81 0
[48.52]
8
45,X/46,XX 102 0
[27:73] 9
45,X/47,XXX 96 0
[37:63] 10
46,XX/47,XXX + +
[90:10] 11
Mean (SD) 37.3 (26.5) 68.5 (9.7) 102.0 (20.0)
47,XXX
12 0 12 50 + 109 0 0
13 + 3 48 + 80 + PT
14 0 <1 47 + 70 + PT
15 + <1 41 + 73 0 FT
16 0 50 67 0 112 0 0
17 0 3 46 + 90 + FT
18 + <1 41 + 53 + FT
19 + <1 52 + 105 + PT
20 + <1 41 + 76 + FT
21 + 1 56 + 77 + PT
Mean (SD) 7.4 (15.3) 48.9 (8.1) 84.5 (19.1)
Control
22 ND 42 68 0 94 0 0
23 ND 66 78 0 83 + PT
24 ND 69 75 0 128 0 0
25 ND 27 66 0 112 0 0
26 ND 38 77 0 89 0 PT
27 ND 8 61 + ND ND ND
28 ND 69 78 0 ND ND 0
29 ND 24 71 0 ND 0 ND
30 ND 38 75 0 105 0 0
31 ND 24 65 0 87 + PT
32 ND 82 74 0 120 0 0
Mean (SD) 44.3 (23.7) 71.6 (5.8) 102.3 (16.6)
0 0
* Symbols and abbreviations: +, present; 0, absent; ND, no data;PT,parttime; FT, full time;
ratio; BOTMP, Bruininks-Oseretsky Test of Motor Proficiency.
subtests were not significantly different from the 47,XXX control subjects (Table 2). They did relatively well
on the clinical assessment with a
Neurologic/Sen-sory-Motor Integration score mean of 68.5, which
was not significantly different from that of the
control girls at 71.6.
],
newborn chromosomeNine
of the ten girls with 47,XXX had BOTMPcomposite percentiles at or below 12, except for
subject 16 with 50% (Table 1). Both the gross motor
and battery composite standard scores were
ARTICLES 681
TABLE 2. Comparison of Standard Score Means of Aneuploid Subjects to Controls on Bruininks-Oseretsky Test of
Motor Proficiency Subtests and Battery Composites*
Test ‘ Controls (n
45,X (n = 5) 47,XXX (n = 10) Mosaics (n = 4) 11)
Mean SD P Value Mean SD P Value Mean SD P Value Mean SD
Gross motor
Running speed and agility 22.8 1.8 .0041 22.4 1.3 .0006 29.0 7.4 .1038 34.9 11.8
Balance 35.6 11.4 .0021 36.0 13.8 .0004 43.0 10.5 .0441 54.5 8.3
Bilateral coordination 344 13.8 .0002 42.2 11.1 .0019 58.0 10.1 .3392 55.6 4.9
Strength 31.2 12.6 .0048 30.6 12.2 .0008 56.0 19.0 .2928 51.6 13.0
Gross and fine motor: upper- 24.0 3.5 .0001 29.4 6.9 .0001 45.5 6.6 4798 45.3 9.5
limb coordination Fine motor
Response speed 31.6 8.6 .0512 34.8 10.5 .0785 370 12.5 .2254 42.2 13.1
Visual-motor control 36.0 17.4 .0074 52.0 13.1 .4581 60.0 4.0 .1435 52.5 8.8
Upper-limb speed and dex- 31.2 7.0 .0017 33.8 11.4 .0011 46.5 13.8 .3536 48.7 8.3
terity
Gross motor composite 25.6 10.9 .0001 28.1 9.3 .0001 46.3 9.9 .2585 50.1 10.3
Fine motor composite 27.2 13.5 .0010 36.5 13.7 .0165 47.0 8.7 .4942 46.9 5.2
Battery composite 24.6 10.3 .0001 27.7 10.1 .0001 46.0 8.2 .3310 48.3 6.8
* All scores were converted to a mean of 50 with a SD of 10. A one-way analysis of variance was conducted on all of
the scores. Each SCA group was contrasted with the control group using a one-tailed significance level of P = .002,
obtained by dividing the number of subtest contrasts by a composite a of .05.
icantly below the control girls, although they per-formed relatively stronger on fine motor tasks. The
subtest profile was consistent with these results
(Table 2). Nine girls with XXX received clinical
Neurologic/Sensory-Motor Integration scores that
were at or below 56 (range 16 to 80) and lower than any control subject. In contrast, subject 16 received a score of 67, which was consistent with the control girls and her prior positive test results. Nine of the
10 girls with 47,XXX showed evidence of
sensory-motor integration dysfunction (Table 1). Low tone
was present in six girls and was associated with diminished strength, poor joint stability, and gait abnormalities. At least 7 of the 10 subjects
experi-enced difficulty with balance, rapid alternating
movements (diadokokinesis), motor planning, and
bilateral coordination. These problems were
evi-dent in both gross and fine motor skills. They also
experienced difficulty with visual perception,
vis-ual-motor integration, and prehension.
Control Subjects
The control group performed significantly better than the nonmosaic 45,X and 47,XXX aneuploid groups. Only control subject 27 had a BOTMP
battery composite percentile of 8, and the other 10
had percentiles of 24 and above. Their clinical
Neurologic/Sensory-Motor Integration scores had
a mean of 71.6 of a maximum of 80, and in only
subject 27 was dysfunctional sensory-motor
inte-gration diagnosed. The control subjects’ BOTMP
composite standard scores were consistent with the test standardization sample.
Early Motor Development
The age at which each proposita achieved the
developmental milestone of independent walking
was compared to the standardization data of the Denver Developmental Screening Test which
mdi-cated that 90% of all girls were walking by 14.8months. Of the entire 21 propositae, 11 (52%) were
delayed in this area when the Denver
Develop-mental Screening Test criteria were used; they
walked independently at 15 to 22 months of age
(Table 1). This is a marked increase in motor
developmental failure relative to the normative
population for this item.
DISCUSSION
The 45,X and 47,XXX propositae frequently
ex-hibited both gross and fine motor dysfunction.
Their neuromuscular evaluations documented
hy-potonia associated with joint instability and
sen-sory-motor integration dysfunction which ad-versely affected coordination, visual-motor integra-tion, joint stability, and strength. Of 15 girls, 12
(80%) had BOTMP battery composite scores below
the 10th percentile. Their subtest profiles were
relatively flat, although girls with XXX performed slightly stronger on fine motor tasks.
The BOTMP scores were consistent with the
clinically derived Neurologic/Sensory Motor
Inte-gration scores. These scores for control subjects
ranged from 61 to 78 of a maximum 80 and
mini-mum 16. With the exception of one 45,X girl who
achieved a 75 and a 47,XXX girl with a 67, there
was no overlap between the aneuploid and control
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subjects. Only one control girl was identified as
having sensory-motor integration dysfunction, in
contrast to 13 of 15 subjects with monosomy X and
xxx.
The partially monosomic
x
chromosome variantsand the sex chromosome mosaics are more similar
to
the controls.
One ofthe
six girls,45,x/46,x,r(x),
who had a Turner syndrome phenotype, had a
BOTMP battery composite score below the 10th
percentile. Subject 10 who was a
xixxx
mosaichad an adequate clinical score and no other
devel-opmental problems. The
Neurologic/Sensory-Mo-tor Integration scores for this group were 55 to 77 of the possible 16 to 80, and only one demonstrated sensory-motor integration dysfunction.
A
retrospective review of the age of independentwalking confirms the consistency of motor
devel-opmental dysfunction throughout time. Of 15 girls with 45,x and
47,xxx,
9 walked after 15 months of age, in contrast to the expected 10% of thegeneral population. All propositae walked
inde-pendently by 22 months of age.
In addition to the early motor delay, other areas of difficulty were identified independently at differ-ent ages. These included 11 of 15 girls with 45,X and
47,xxx
with a moderate to severe language dysfunction, and 12 of 15 who were independently referred for full- or part-time educational special services. The 3 nonmosaic subjects with the fewestdevelopmental problems and no special education
referral had the highest IQ scores as determined on
the Weschler Intelligence Scale for Children.
De-velopmental concerns were rare among the sex
chromosome mosaics and control subjects.
Results of this study indicate that gross and fine
motor delays associated with a mild to moderate
sensory-motor integration dysfunction are frequent findings in this group of girls with 45,X and
47,xxx.
Although our number of 45,X subjects is small, there are indications that this group has amore global neurologic dysfunction than is
gener-ally recognized. The study of sensory-motor
inte-gration by Ayres’#{176}suggested that adequate feedback
and integration of the sensory modalities are
nec-essary for maximal function of an individual. Dys-functional sensory-motor integration is likely to be an additional factor that adversely influences class-room performance. In addition to affecting learn-ing, the decreased perceptual organization may also
contribute to a diminished self-concept and
made-quate peer interaction.
It is our conclusion that sex chromosome
aneu-ploidy in girls is associated with an increased risk
for sensory-motor integration dysfunction. This is
likely to be an additional factor that negatively
influences classroom performance along with
lan-guage delays and depressed cognitive abilities.
There is variability within the groups, and mosaic
subjects are developmentally closer to the control subjects. The longitudinal assessment has also sug-gested that sex chromosome aneuploid subjects
demonstrate an increased vulnerability to adverse
environmental conditions.” Continued evaluations with a greater number of subjects is desirable.
We encourage regular developmental
assess-ments to provide anticipatory guidance through early identification and intervention.
Neuromus-cular status and sensory-motor integration should
be a part of the ongoing periodic evaluation in
children with sex chromosome aneuploidy, and
ap-propriate intervention should be recommended.
ACKNOWLEDGMENTS
This study was supported, in part, by grant
5R01-HD10032 from the US Department of Health and Human
Services, Public Health Service; grant RR-69 from the
General Clinical Research Centers Program of the
Divi-sion of Research Resources, National Institutes of
Health; and The Genetic Foundation.
The authors thank Dr John F. LaBrecque for statisti-cal consultation and Jean Clyne for help in preparation
of the manuscript.
REFERENCES
1. Jacobs PA. The incidence and etiology of sex chromosome abnormalities in man. Birth Defects. 1979;15:3-14
2. Robinson A, Bender B, Borelli J, et al. Sex chromosornal aneuploidy: prospective and longitudinal studies. Birth
De-fects. 1986;22:23-71
3. Linden MG, Bender BG, Robinson A. 47,XXX: what is the prognosis? Pediatrics. 1988;82:619-630
4. Bender B, Fry E, Pennington B, Puck M, Salbenblatt J, Robinson A. Speech and language development in 41
chil-then with sex chromosome anomalies. Pediatrics.
1983;71:262-267
5. Pennington BF, Bender B, Puck M, et al. Learning disabil-ities in children with sex chromosome anomalies. Child Dev. 1982;53:1182-1192
6. Salbenblatt JA, Meyers DC, Bender BG, Linden MG, Ro-binson A. Gross and fine motor development in 47,XXY and 47,XYY males. Pediatrics. 1987;80:240-244
7. Bender B, Puck M, Salbenblatt J, Robinson A. Cognitive development of unselected girls with complete and partial
x
monosomy. Pediatrics. 1984;73:175-1828. Bruininks RH. Bruininks-Oseretsky Test of Motor Profi-ciency, Examiner’s Manual. Circle Pines, MN: American Guidance Service; 1978
9. Frankenburg WK, Dodds JB, Fandal AW, et al. Denver
Developmental Screening Tests, Manual. Denver, CO: Uni-versity of Colorado Medical Center; 1967
10. Ayres AJ. Sensory Integration and Learning Disorders. Los Angeles, CA: Western Psychological Services; 1972
11. Bender BG, Linden MG, Robinson A. Environment and
1989;84;678
Pediatrics
Robinson
James A. Salbenblatt, Deborah C. Meyers, Bruce G. Bender, Mary G. Linden and Arthur
Gross and Fine Motor Development in 45,X and 47,XXX Girls
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