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Introduction
Monosomy 5p (cri-du-chat syndrome), first described in 1963 by Lejeune
et al., is a well-recognized clinical entity, and the diagnosis can readily be
made at birth. The diagnosis of trisomy 5p, however, is more difficult and
usually made only on chromosome analysis. We report the case of a child
tri-somic for chromosome segment 5p13.32 ? 5p14.31 due to a
re-combination aneusomy (Lejeune and Berger 1965).
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Case reportHaut
Clinical history
The propositus (IV 2, Fig. 1) was born on January 20, 1987 at 39
weeks gestation, following an uneventful pregnancy. At birth he weighed 3000 g
and measured 47 cm, and his head cir-cumference was 36.5 cm. Both parents (III
6 and III 7) were in good health. The mother had had one spontaneous
miscarriage at 8 weeks of pregnancy (in 1985). The family pedigree was
unremarkable except for the child III 1 (a son of the paternal uncle of the
propositus), who was born with hydrocephalus and who died a few hours after
birth.
 Fig.l. - Family pedigree. White square with black dot :
46,XY,inv ins(5)(p15.12;p14.2;p14.3), Black square :
46,XY,der(5)(p15.12;p14.2;p13.31)pat
 Fig. 2. Propositus at 2 months of age
When examined at 2 months of age (Fig. 2), the propositus weighed
4300 g (P 10-25) and measured 51 cm (< P5), and his head circumference was
40 cm (P 50-75). Generalized hypotonia was noted. His forehead was high with
retraction of the temporal regions, which contrasted with his round face and
prominent cheeks. The occipital bone was protuberant. His upper eyelids were
puffy, and epicanthal folds were present. The palpebral fissures were small due
to mild blepharophimosis and were horizontally slanted. The irides were blue
and cryptic, and he had coloboma of the iris and retina bilaterally. His nose
was short with a broad, flat bridge and large septum, through which ran a
median groove. The pillars of the philtrum were poorly marked. His mouth was
small with a short upper lip and a thick, everted lower lip. Glossoptosis was
present, due to posterior positioning of the tongue. He showed
micro-retrognathia. His ears were low set. The superior border of the helix was
horizontal bilaterally. The left antihelix formed a single crest, which ended
with one prominent fold. Just behind the antitragus a small unusual pitlike
cutaneous depression was noted; the superior half of the pinna hung down
loosely.
His neck was short and wide. His abdomen, was prominent secondary to
hypotonia. An umbilical hernia and major diastasis recti were noted. The testes
were in the scrotum; the penis was large and angulated. He had bilateral
clubfoot. The toes of his right foot were irregularly implanted and overlapped,
the first toe overlapping the second and the fourth overlapping the third. In
both hands the flexion creases were normal. His fingers were long, with a
radial loop on the thumb and IV, and arches on II, III and V, bilaterally.
At 1 year of age the child weighed 9000 g (P 10-25) and measured
74.5cm (P 25), and his head circumference was 49.5cm (P 95). His skull was
turricephalic with depression of the temporal regions. His face, especially the
cheeks, appeared infiltrated. Developmental milestones were only slightly
delayed: he smiled, had social contact, and sat without support, but did not
stand; he was capable of only monosyllabic vowel sounds. The D.Q.
(Brunet-Lezine) was 75.
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Cytogenetics
Cytogenetic analysis (Figs. 3, 4) of the proband's peripheral blood
lymphocytes revealed a male karyotype with 46 chromosomes. In all the mitoses
analyzed, the short arm of one chromosome 5 was too long. After RHG-banding, it
was seen that band 5p15.1 was too marked and that zone 5p14 was slightly
elongated. The other chromosomal segments appeared normal.
The maternal karyotype was normal. The paternal karyotype analyzed
by RHG-banding revealed that in spite of normal total arm length, the short arm
of one of the chromosomes was structurally abnormal. Band 5p15.1 was too
prominent (as observed in the propositus), whereas band 5p13.3 was extremely
small. The other chromosomes were normal. Karyotype analyses done in
prometaphase (Viegas-Pequignot and Dutrillaux 1978) showed that both father and
son had a chromosomal anomaly that was limited to the short arm of one
chromosome 5. As is seen in Fig. 3. the paternal karyotype analyzed by
RHG-banding showed an exaggeration of band 5p15.1, reduction of band 5p13.3,
and a very minute, colored band at 5p14.2, which was absent on the normal
homologous chromosome. This arrangement could arise from three breakpoints (at
5p13.31, 5p14.3, and 5p15.12) and inverted translation of chromosome segment
5p13.32 ? 5p14.2, the segment 5p125.11 ? 5p14.3 keeping its
normal centromeric orientation.
During paternal meiosis, the translated and inverted segment
(13.32-14.2) could remain unpaired, forming translation loops (see Fig.3A). One
chromatid exchange (or an odd number of exchanges) in the paired segment
(14.3-15.11) could have produced the recombinant chromosome observed in the
propositus. A double loop figure could also have occurred if the inverted
translated segment also pairs (see Fig.3B). If the single chromatid exchange
(or odd number of exchanges) in segment (14.3-15.11) produced the recombinant
chromosome, then the propositus is trisomic only for chromosome segment 5p13.32
? 5p14.2 (46,XY, inv ins(5)(pter ? p15;12: :p13.32 ?
p14.2::p15.11 ? p14.3:: 13.31 ? qter). The balanced
inversion-insertion described in the proband's father was also found in the
paternal grandfather (II3, Fig. 1) and in the paternal great uncle (II3). The
rest of the kindred could not be examined.
 Fig. 3. - Meiotic
pairing and crossing-over in an inv ms(5)(pter ? p15.12::p13.32 ?
p14.2::p15.11 ? p14.3::13.31 ? qter) resulting in recombinant
chromosome 5 with duplication of the 5p13.32-^5p14.2 segment. A Simple
translation loops, B double-loop figure
 Fig.4a,b* - Chromosomes 5: a of the proband; b of the father. The
arrows show the abnormal chromosomes. R bands and G bands
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Discussion
Cases of isolated trisomy or monosomy resulting from a parental
translation and subsequent recombination aneusomy have been reported (Lejeune
and Berger 1965). Review of the literature revealed nine cases similar to our
observation. Five of these cases showed inverted insertion (Gustavson et al.
1988; Kajii et al. 1987; Martin et al. 1985; Palmer et al. 1977; Wyandt et al.
1980), and one case, an intrachromosomal direct shift (Therkelsen et al. 1973);
in the remaining cases (Cohen et al. 1983; Narahara 1987; Pai et al. 1983) the
displaced segments were so small that they precluded any interpretation
pertaining to their centromeric orientation. In three of the reported cases,
translation of the chromosomal segment occurred within the chromosome arm
(Kajii et al. 1987; Nara" hara 1984; Wyandt et al. 1980). Parental translation
was of maternal origin in five cases and of paternal in the remaining four
observations.
Since the first reported observation of trisomy 5p in 1964 (Gustavson
et al. 1964; Lejeune et al. 1964) about forty other cases have been reported.
Most of the cases arise from translocations involving the short arm of
chromosome 5 and another autosome. These partial trisomies for the short arm of
chromosome 5 are therefore associated with other chromosomal
disequilibriums.
We were able to find nine other reports of isolated trisomy 5p. Six of
these were complete 5p trisomies (Brimblecombe et al. 1977; Carnevale et al.
1982; Cordero et al. 1977; Kunze et al. 1980; Leschot and Lim 1979; Orye et al.
1983); and resulted either from the formation of an isochromosome for the short
arm of one chromosome 5 or from a translocation of 5p onto the centromere of an
acrocentric chromosome. Klecz-kowska et al. (1987) reported a patient with an
isolated partial trisomy 5p resulting from a tandem duplication of segment
5p13.1 ? 5p15.3. This polymalformed infant had hydrocephalus, agenesis
of the corpus callosum, abnormal fixation of the jejunum and of the ascending
colon, hypoplastic polycystic kidneys, and small adrenal glands with marked
cortical hypoplasia. Marked hypertelorism, narrow palpebral fissures with a
mongoloid slant, poorly lobulated ears, and microretrognathia were noted. The
limbs were long and slender and both thumbs were in fixed adduction. The
patient had bilateral clubfeet but no other skeletal anomalies were documented
on X-ray.
The patient reported by Gustavson et al. (1988), trisomic for segment
5p13 ? 5p15, had moderate macrocephaly, a prominent forehead, and a
protruding occiput. The nose was short with a broad, flat nasal bridge. The
photograph (Fig. 2) of the child shows, as in our patient, a wide nasal septum
with a median groove. The patient had alternating convergent strabismus,
luxation of the right hip, and equinovarus deformity of the feet. At age 5
years her I.Q. was 45. A CT scan showed slight enlargement of the ventricles
without hydrocephaly.
A case of trisomy 5p resulting from a de novo tandem duplication was
reported by Chia et al. (1987). The patient was trisomic for the distal portion
of the short arm of chromosome 5: 5p14 ? 5pter. Dysmorphic features were
minimal (bifid tip of the tongue, bilateral genu valgus, and slightly
wide-spaced nipples), and the developmental delay was mild (IQ of 68 at age 4
2/12 years).
The clinical picture of our patient is very similar to the one
described by Gustavson et al. (1988) and is less severe than that reported by
Kleczkowska et al. (1987), whose patient also had macrocephaly, small palpebral
fissures, hypertelorism, micrognathia, and equinovarus deformity of the
feet.
From these observations and as already suggested by Leschot and Lim
(1979) and by Orye et al. (1983), it would seem that the clinical severity of
trisomy 5p is due not only to the length of the duplicated segment, but perhaps
essentially to trisomy for all or part of segment 5p13.
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References
Brimblecombe FSW, Lewis FJ, Vowles M (1977) Complete 5p trisomy: 1
case and 19 translocation carriers in 6 generations. J Med Genet 14:271-275
Carnevale A, Hernandez M, Limon-Toledo I, Frias S, Castillo J,
DelCastillo V (1982) A clinical syndrome associated with dup (5p). Am J Med
Genet 13:277-283
Chia NL, Bousfield LR, Johnson BH (1987) A case report of a de novo
tandem duplication (5p)(p14 ? pter). Clin Genet 31:65-69
Cohen MM, Lemer C, Balkin NE (1983) Duplication of 16p from insertion
of 16p into 16q with subsequent duplication due to crossing over within the
inserted segment. Am J Med Genet 14:89-96
Cordero JF, Miller WA, Liberfarb RM, Atkins L, Holmes LB (1977)
Trisomy 5p: a variable phenotype. Pediatr Res 11:535
Gustavson KH, Finley SC, Finley WH, Jailing B (1964) A 4-5/21-22
chromosomal translocation associated with multiple congenital anomalies. Acta
Paediatr Scand 53:172-181
Gustavson KH, Lundberg PO, Nicol P (1988) Familial partial trisomy 5p
resulting from segregation of an insertional translocation. Clin Genet
33:404-409
Kajii T, Matsuura S, Murano I, Kuwano A (1987) Inverted insertion
(9)(q34.3q22.3q21.2) and its recombination product duplication 9q21.2q22.3. Jpn
J Hum Genet 32:45-48
Kleczkowska A, Fryns JP, Moerman P, Berghe K van den, Berghe H van den
(1987) Trisomy of the short arm of chromosome 5: autopsy data in a malformed
newborn with inv dup (5)(p13.1 ? p15.3). Clin Genet 32:49-56
Kunze J, Johs R, Tolksdorf M (1980) Totale trisomie 5p bei
mutter-licher balancierter Translocation: 46,XX inv ins (1;5)(p32 oder 34;pter
p11). (Klinische Genetik in der Pädiatrie 2) Thieme, Stuttgart, pp 201-202
Lejeune J, Berger R (1965) Sur deux observations familiales de
translocations complexes. Ann Génét (Paris) 8:21-30
Lejeune J, Lafourcade J, Berger R, Vialatte J, Boeswillwald M, Seringe
P, Turpin R (1963) Trois cas de délétion partielle du bras court d'un
chromosome 5. CR Acad Sci Paris [III] 257:3098-3102
Lejeune J, Lafourcade J, Berger R, Turpin R (1964) Segregation
familiale d'une translocation 5-13 determinant une monosomie et une trisomie
partielles du bras court du chromosome; 5: maladie du cri du chat et sa
réciproque. CR Acad Sci [III] 258:5767-5110
Leschot NJ, Lim KS (1979) Complete trisomy 5p: de novo translocation
t(2;5)(q36;p11) with isochromosome 5p. Hum Genet 46:271-278
Martin NJ, Cartwright DW, Harvey PJ (1985) Duplication 5q (5q22
? 5q33): from an intrachromosomal insertion. Am J Med Genet 20:57-62
Narahara K (1987) Dir Ins(9)(q34.3q22.1q31.3) or inv
Ins(9)(q34.3q22.3q21.2)? Jpn J Hum Genet 32:49-50
Orye E, Benoit Y, Van Mele B (1983) Complete trisomy 5p owing to de
novo translocation t(5;22)(q11;p11) with isochromosome 5p associated with a
familial pericentric inversion of chromosome 2, inv2(p21q11). J Med Genet
20:394-395
Pai GS, Rogers JF, Sommer AM (1983) Identical multiple congenital
anomalies mental retardation (MCA/MR) syndrome due to del(2) (q32) in two
sisters with intrachromosomal insertional translocation in their father. Am J
Med Genet 14; 189-195
Palmer CG, Christian JC, Merritt AD (1977) Partial trisomy 1 due to a
"shift" and probable location of the Duffy (Fy) locus. Am J Hum Genet
29:371-377
Therkelsen AJ, Hulten MAJ, Jonasson J, Lindsten J, Christensen NC,
Inversen R (1973) Presumptive direct insertion within chromosome 2 in men. Ann
Hum Genet 36:367-373
Viegas-Pequignot E, Dutrillaux B (1978) Une méthode simple pour
obtenir des prophases et des prométaphases. Ann Génét (Paris) 21:122-125
Wyandt HE, Kasprzak R, Ennis J, Willson K, Koch V, Schnatterly P,
Wilson W, Kelly TE (1980) Interstitial 3p deletion in a child due to paternal
paracentric inserted inversion. Am J Hum Genet 32: 731-735
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