Only a few subjects have been reported to have congenital autosomal
monosomy. Most of them have been mosaics with one 45,-G cell line and one or
two more cell lines with a normal karyotype and/or a structural chromosome
abnormality involving a G chromosome (reviews in Greenwood and Sommer 1971 and
Weber et al. 1971) (Emberger et al. 1970). To our knowledge only four
congenital, apparently non-mosaic cases with presumptive G monosomy have been
published (Thorburn and Johnson 1966, Al-Aish et al. 1967, Hall et al. 1967 and
Gripenberg et al. 1972). In one of these cases the karyotype was interpreted as
45,X,-21 by quinacrine fluorescence analysis (Gripenberg et al. 1972). In the
present paper we report on a 54 years old mentally retarded woman who
originally was considered to have a presumptive monosomy 21 on the basis of an
analysis of the direct Giemsa (G) and quinacrine (Q) chromosome banding
patterns. However, later studies using the reversed Giemsa (R) banding
technique demonstrated an unbalanced 4q/21 q translocation.
The patient, a female born in 1919, was an only child, and the mother
had probably not had any spontaneous abortions. Nothing is known about the
pregnancy and the delivery or about the birth weight of the patient. The mother
was German and the father Swedish, and thus there was no consanguinity. Her
father was 39 and her mother 32 years old at her birth. The father died when
the patient was young. The mother died in 1967, and since then the patient has
been taken care of in an institution for the mentally retarded. There is almost
no information available about the patient before 1967, but she had apparently
been healthy and was not unusually susceptible to infections. No other cases of
mental retardation or malformations are known in the family.
At the last examination, at 54 years of age, the following
observations were made (fig. 1). Short stature with body height 140 cm, weight
43.5 kg and head circumference 54.5 cm. She was blind and had congenital
microphtalmia. There were no other obvious external malformations, but her
hands and feet were rather slender. The secondary sex characteristics were
normal for the age, but it was not possible to obtain information regarding
menstruation and age at climacterium.
She walked with raised arms as blind persons do, and needed some
support. Her reflexes were rather strong, Babinski's sign could not be
elicited. Twice before and four times after 1967 she had had fractures which
included the collum of the femur, the fingers and the ankles. X-ray examination
revealed generalised osteopenia. The joints were normal. Her hearing was also
apparently normal. Physical examination gave no evidence of a heart
malformation. The palate was normal, but there was a moderate overcrowding of
the incisors in both jaws.
The patient's native language was German, and she spoke German as well
as Swedish fluently. She was well orientated in time and space and had a very
goad memory. Some help with her personal care was needed. She was even tempered
and good natured. Only a very rough estimate of the intelligence quotient could
be made because of her blindness. The intelligence profile was apparently very
uneven. The memory was rather good and the vocabulary (in Swedish) correspond
to an IQ of 65. The ability to understand and draw conclusions was considerably
reduced, the IQ being about 50.
Fig. 1. - The patient at 54
years of age: a) full picture; b) face
The patient was sex chromatin positive in cells from buccal mucosa
smears. A 45,XX,-G karyotype was consistently found in repeated lymphocyte
cultures and one fibroblast culture of a skin biopsy. One hundred cells were
analysed from each tissue.
Analysis of the banding pattern of the chromosomes after quinacrine
(Caspersson et al., 1971) and Giemsa (Summer et al. 1971 ) staining showed only
one chromosome 21, but an otherwise normal female karyotype (fig. 2). However,
evidence in favour of an unbalanced 4q/21q translocation was obtained by the
reversed Giemsa banding technique (Dutrillaux and Lejeune, 1971). As seen from
figure 3 the normal chromosome 21 has a prominent dark band at the end of the
long arm. A similar band can be seen at the end of the long arm of one
chromosome number 4, which normally has a tiny dark band in this region. No
measurable size differences were found between the two chromosomes number 4.
There were no other obvious abnormalities noted.
Analysis of genetic markers.
A number of genetic markers were analysed at different laboratories
(see Ackowledgments), and the following results were obtained. Blood groups: B;
MN; ss; P1; R1 R2,; K+ k+; FYa+ FYb+; JKa- Jkb+; Lua- Lub+; Lea- Leb-; Coa + .
Serum protein groups: Hp 2-2; Tf C; C'3 2; Pi M; Gc 2-1; Gm (+ 1,-2,+ 4,+5,+
10,+14,+17); Inv ( - 1). Red cell enzymes:AcP BA; PDG A; PGM1 2-1; PGM3, 2-1;
AK 2-1 ; ADA 1; Pep A,B,C,D 1 ; GPT 2-1. HL-A, typing showed the presence of
four antigens (1, 2, LNDx, SL-ET). Thus, the patient was clearly heterozygous
at the following 12 loci: MN; Rh; Kell; Duffy; Gc; acid phosphatase,
phosphoglucomutase 1 and 3, adenylate kinase, glutamate-pyruvate transaminase,
HL-A and most likely Gm.
The finger print patterns (fig. 4), six whorls and four ulnar loops,
are not typical of Down's syndrome; in mongols whorls are reduced in number but
ulnar loops show a high frequency.
The total ridge count (212) is well above the average for English
female mongols (124) and even higher than that found in Turner's syndrome
(169); mongols tend to have, on the average, a. slightly lower total ridge
count than the general, population (O 127, S.D. 52).
On the palms, the presence of a peripheral loop III on the right
side, and the distal position of the axial triradius (t') on both sides, are
dermatoglyphic features which are not against the diagnosis of mongolism.
Pattern intensity, however, is low; the mean number of loops per palm is here
1.0 against 1,88 in English mongols (males and females combined), and the
absence of pattern in the hypothenar area is not characteristic of 21 trisomy;
in mongols a peripheral loop H occurs with a frequency of 66.5 per cent.
On the soles, dermatoglyphic features characteristic of Down's
syndrome such as an open field an the hallucal area of the sole or a distal
loop on area IV are not present in the patient's soles. She has, however, a
distal loop I an the hallucal area of bath soles but the quality of the prints
did not permit measurement of the size of the loop.
A small distal loop I containing 20 or less ridges is about three
times as common in mongols as it is in controls while large loops, ridge count
over 20, have in female mongols a frequency of 15.5 per cent on the left : and
right soles but of 45.5 and 47.3 per cent, respectively, in English female
The zygodactylous z triradius which seems to be present on the left
sole is rare in mongolism.
Finally, the anti-mongol tendency shown by the patient's
dermatoglyphic configurations was ascertained by calculating the probability of
her being a mongol (Penrose and Smith 1966, Holt 1968 and Penrose and. Loesch
1971). This probability was found to be between 1 /30 to 1 /750 (the
discriminant value x = 5050).
Fig. 2 - Quinacrine (a) and
Giemsa (b) stained karyotypes showing a presumptive 45, XX, - 21 chromosome
constitution wihout evidence of a translocation.
It has generally been assumed that congenital autosomal monosomy in
man would be very rare, since it would very likely be too genetically
unbalanced for survival. In fact, very few such eases have been reported, and
most of them have been mosaics involving one chromosome in the G group. Even
among spontaneous abortuses autosomal monosomy seems to be very rare indeed
(Larsson et al. 1970, Carr 1971). Only the case of Gripentberg et al. (1972)
has to our knowledge been analysed with regard to the chromosome banding
pattern. This case was reported to have a presumptive monosomy 21.
Originally the present patient was also considered to have monosomy
21. However, several observations did not seem to favour this interpretation.
Firstly, the patients somatic defects were relatively limited, as in the case
of Gripenberg et al. (1972). This could of course be explained by a
non-detected mosaicism, a possibility which seems unlikely but can not be
completely ruled out. Secondly, if monosomy 21 is not associated with more
severe anomalies, it should have been recognized among the offspring of D/21
and 21/22 translocation carriers. To our knowledge no such case has been
described, and it is highly unlikely that it has been overlooked. Thus, even if
the present patient originally appeared to have a pure monosomy 21, a
translocation involving one chromosome 21 could not be totally excluded, and in
fact an unbalanced 4q/21 q translocation was later demonstrated.
The translocation could only be identified by an analysis of the
R-banding but not by the G- and Q banding patterns. This is due the fact tree R
technique gives a particular clear staining of those chromosome tips which are
weakly stained with the other methods. In the present case the distal end of
chromosome 21, which has a prominent dark R-band, had apparently been
translocated on to the distal end of chromosome 4. This could be demonstrated
only because the R-band at the tip of the normal chromosome 4 is very much
smaller than the one on chromosome 21. Since the fluorescent band on the middle
of the long arm on chromosome 21 X21 q21) could not be seen on either
chromosomes 4, the break on chromosome 21 has probably occurred in the proximal
part of band 21q22 (nomenclature of the Paris Conference 1971). The exact
location of the break point on the long arm of chromosome 4 could not be
evaluated. Since both chromosomes 4 were of the sage size the break point ought
to be located in or distal to band 4q33.
Fig. 3. - Reversed
Giemsa stained karyotype showing a prominent dark band at the end of the long
arm of one chromosome number 4. This band is similar in size to that seen on
the long arm of the only chromosome 21 present.
Fig. 4 - Dermatoglyphic pattern of
the patient's hand (a) and feet (b).
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