HERE 55-19

A CASE OF MENTAL RETARDATION

WITH AN ADDITIONAL SMALL
METACENTRIC CHROMOSOME
By I N G R l D GAMSI’ORP, L E l F HAKANSSON and JAN LAGERGREN
DEPARTMENT OF PEDIATRICS, AND DEPARTMENT OF ANATOMY AND HISTOLOGY,
UNIVERSITY O F LUND, SWEDEN
(Received April 14th, 1966)

INTRODUCTION

S EVI:RAL reports have been published concerning extra autosomes

associated with multiple anomalies and mental retardation, other
than those concerned with the trisomy-syndromes 13-15, 16-18, and
21-22 (e.g. B ~ O Ket al., 1961; CRAWFURD, 1961; BUTLERet al., 1962;
ELLISet al., 1962; GUSTAVSON et al., 1962, 1964; VISLIEet al., 1962;
FRDLAND et al., 1963; TAFTet al., 1965).
In only a few of these cases the extra chromosome is a small meta-
centric one. FRDLAND, HOLST and TERSLEV (1963) described such a
chromosome in a boy with multiple anomalies and mental retardation.
A similar chromosome was found by GUSTAVSON,ATKINS and PAT-
RICKS (1964) in one of two siblings who had extra chromosomes. One of
them, a boy, with mental retardation, microcephaly, epilepsy and
multiple anomalies, particularly of the face, head and mouth, similar
to those described by FROLAND et al. (1963), had a small metacentric
chromosome. His sister was a typical mongoloid with trisomy-21. A
third case, occurring in a 16-month-old boy, was described by TAFT,
DODGEand ATKINS (1965). This boy was mentally retarded, function-
ing at about the 9-month-level. He also had small, low-set ears, epi-
canthal folds, bilateral hammertoes, incurving of both fifth fingers,
bilateral retinal colobomata and increased muscle tone.
The present paper is a report of a mentally retarded girl with an
:idditional small metacentric chromosome.

Methods
Chromosonial preparations were made from skin fibroblasts (meth-
od: HALL,1964) and peripheral blood leukocytes (method: MOORHEAD
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MENTAL RETARDATION 267

et al., 1960, as modified by KALLEN and LEVAN,1962). The autoradio-

graphic procedure was performed according to SCHMID(1963).

CLINICAL FINDINGS
The patient was examined a t the age of six. She is the third child of healthy,
unrelated parents, aged 32 and 34 years, respectively, a t the time of the patient’s
birth. Two elder siblings are healthy and normally developed. One first cousin of
the mother is severely mentally retarded, cause unknown; no other instances of
mental or neurological diseases are known in the family. Pregnancy, delivery, birth
weight (3230 g) and neonatal period were normal. The patient has always been
healthy except for minor upper respiratory infections. Physically she has developed
normally, but her mental development has been slow. This was first observed by
her parents when the girl was about sir months old. She still lacked head control
and paid no attention to toys. Head control was achieved a t the age of 9 months;
she reached out for objects at 10 months, could sit without support at 15 months,
walked by herself at 22 months, was toilet trained at 3 years and started to use
single words at age 4.
At examination, the girl was found to have a n essentially normal physical appear-
ance (Fig. 1). Her height, 119 cm, and weight, 17 kg, are normal for her age. Head
circumference, 46,5 cm, is about 4 cm less than the average for her age. Routine
physical examination revealed no abnormalities. A straight and low hairline in the
neck, overstretchability of finger joints, a slightly stiff gait, clumsy small-finger
movements, and convergent strabism (about Z O O ) were observed; the result of the
neurological examination, including otoneurological and ophthalmological examina-
tions, was otherwise normal. Dental development was normal.
Routine blood and urinary tests were normal. A normal amount of amino acids
was found in the urine; phenistix was negative. The spinal fluid contained 2 cells

Fig. 1. The patient six years old.

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268 INGRID GAMSTORP. LEIF HAKANSSON AND JAN LAGERGREN

per mm', protein was 30 mg per 100 ml with a normal electrophoresis. EEG was
interpreted as mildly abnormal because of a n increased amount of diffusely spread
slow activity.
X-ray of the skeletal system, heart, and lungs revealed no abnormalities. Three
attempts at pneumoencephalography failed, as no gas passed into the, ventricular
system; the filled basal cisterns were normal. Carotid arteriograms were performed
on both sides with normal results. A vertebral arteriogram revealed no abnormalities
in the posterior fossa. A peculiar distribution of vessels was noted: The posterior
inferior cerebellar artery started on the left side from the upper part of the vertebral
artery and on the right side from the basilar artery, and the right superior cerebellar
artery was doubled. These findings were considered a n anomaly of no clinical
significance.
The girl's speech was immature. She spoke in simple sentences and her arti-
culation and vocabulary were poor for her age. Her drawing was immature, mainly
scrawling. Her play was purposeless and unconcentrated. Formal testing (Terman-
Xlerrill) gave a n IQ of 4 0 4 5 .

CYTOGENETIC FINDINGS
The karyotypes of both leukocytes and skin fibroblasts contained 47
chromosomes (Fig. 2). Thirty leukocyte nietaphases and 10 fibroblast
nietaphases were studied and all showed the same karyotype. The extra
chromosome was metacentric and too small to belong to the pair No. 19
or 20. The size is comparable with that of the small acrocentric chro-
mosomes (Fig. 3). The buccal smear contained a normal frequency of
Barr-bodies and no other heterochromatic body could be identified in
the cells. We have tried to characterize this extra chromosome auto-
radiographically and found it to be unlabeled during the late S-phase
(intermediate and late as defined by SCHMID(1963)). The karyotypes
of our patient's parents, studied in blood cultures, were entirely normal.

DISCUSSION
The 3 previously reported patients with an additional small nieta-
centric chromosome were all boys. Common to these and the girl pre-
sented here, is mental retardation, their developmental quotients being
roughly between 20 and 65. As the 4 children have been tested at dif-
ferent ages and with different methods, the results are difficult to com-
pare. The two youngest children both had developmental quotients
above 50 ( F R 0 L A N D et al., 1963; TAFT et a!., 1965), whereas the oldest
tested at age 16, had the lowest (GUSTAVSONet d.,1964); the present
patient, tested at age 6, falls inbetween.
There is also a great variability in the physical appearance of these
patients. In accordance with two of the described patients ( F R B L A N D
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269

h
a
x 3
0
a

a
f
MENTAL RETARDATION
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270 INGRID GAMSTORP. LEIF HAKANSSON AND JAN LAGERGREN

Fig. 3. The chromoyomes 16, 19-20, 21-22 and thc small metacentric one (m)
from four different knryotypcs.

et al., 1963; GUSTAVSON et al., 1964) our girl has a small head circum-
ference, but she lacks all other reported abnormalities of face, dentition,
eyes, ears, hands and feet, nor has she increased muscle tone (FROLAND
et al., 1963; GUSTAVSONe f al., 1964; TAFTet al., 1965). Strabism, noted
in our patient, was also observed by TAFTet (11. (I.c.), it was not de-
scribed in the other four patients discussed. Neither overstretchability
of finger joints nor a straight posterior hairline was reported by the
previous authors.
The origin of the extra chromosome cannot be determined from our
findings. A deletion of one of the chromosomes of pair No. 1 7 or 18, or
an isochromosome for the short arms of one of these chromosomes
would reasonably give a metacentric chromosome of a size comparable
to No. 19-20. This has been described by DE GROUCHY et al. (1964)
and others. CRAWFURD et al. (1965) described a non-mongoloid girl
with an extra small metacentric chromosome and only three small
acrocentrics. Also that metacentric chromosonie was of the size of
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MENTAL RETARDATION 271

19-20 and was interpreted as a translocation between the long arms

of two small acrocentrics. The metacentric chromosome described in
the present paper is smaller than that-furthermore, four small acro-
centric chromosomes exist. It may be suggested that the small nieta-
centric chromosome is an isochromosome for the short arms of the
chromosomes 21-22 but might also represent a centric fragment of
any chromosome in the complement.

SUMMARY
This report is concerned with a six-year old mentally retarded girl
with a small head circumference but no gross physical abnormalities.
She had an additional metacentric chromosome, smaller than chromo-
somes 21-22. It was not labeled autoradiographically during the late
S-phase. The karyotype of both her parents was normal.

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272 INGRID GAMSTORP, LEIF HAKANSSON AND JAN LAGERGREN

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