The incidence of balanced chromosomal translocations, not including
Robertsonian translocations in newborn infants, is between 0.18% [Hook et al.,
1989] and 0.29% [Jacobs, 1990]. The chance mating of 2 such carriers and the
identification of a carrier of 2 different reciprocal translocations from such
a mating is rare. To our knowledge, only 4 cases have been reported [De Grouchy
et al., 1972; Mulcahy et al., 1983; Hansen et al., 1983; Neu et al.,1988].
The occurrence of a second reciprocal translocation in the family of
one of these carriers has never been reported.
We report on an infant with static antenatal encephalopathy and
epilepsy resulting from a chromosomal imbalance inherited from his t(5;10)
carrier father. He also carries a t(3;4) balanced translocation inherited from
his mother. A carrier with a different translocation t(15;21) was identified in
the mother's family.
The propositus, C.M., was born on December 9,1988, to a 25-year-old
gravida 1 woman and her 26-year-old husband. The pregnancy was uneventful.
Delivery was at the 39th week of gestation. Birth weight, length, and head
circumference were 2930 g, 50 cm, and 34.5 cm, respectively.
The child had profound mental retardation. Physical examination
showed a rather distinct appearance (Figs. 1 and 2; Table 1): large face, high
and flat forehead, flat nasal bridge, microphthalmia, horizontal palpebral
fissures, epicanthus, hypertelorism, large and apparently low-set ears,
microretrognathia, and highly arched palate. He also had pyloric stenosis and
complications, including a urinary tract infection at 4 days of life and
feeding problems throughout the first month of life. Neurologically the child
was profoundly hypotonic, with myoclonic seizures treated with carbamazepine
and clonazepam without evident success. There was no eye contact. A pyramidal
syndrome was present. At 18 months, there was no progress in psychomotor
development. He had profound mental retardation and could neither stand nor
walk. He died at 20 month. The parents refused autopsy.
1. - Patient at 20 months.
Fig. 2. - Profile of patient at 20 months.
Fig. 3. - Chromosome pairs involved
in translocations from the propositus (C), mother (A), and father (B). Arrows
indicate translocated segments.
Fig. 4. - Pedigree chewing transmission of each translocation
through 5 generations.
CT scan and MRI showed partial posterior agenesis of the corpus
callosum. Abdominal ultrasound documented normal kidneys, liver, and spleen.
The ophthalmoscopic findings were normal. Bone age was normal. The results of
routine blood and urine analyses were normal.
Amino Acid Analysis
Plasma and urine amino acids were studied by chromatography (Pr. P.
Kamoun and Dr. D. Rabier, Laboratoire de Biochimie Médicale, Hôpital des
Enfants Malades Paris) and were analyzed statistically according to the method
of Lejeune et al. . Performed at 8 months and 20 months of age,
respectively, the 2 examinations showed an increase of the relative
concentration of glutamate and glutamine. The serum glutamate and glutamine
represented 279% of the total amino acids (normal: 208 ± 29), and urinary
excretion of glutamate and glutamine represented 156% of the total amino acids
(normal: 92 ± 29).
Lymphocytes were cultured according to a standard method. Banding
patterns were analyzed using the RHG technique of Dutrillaux et al.  and
the RTBG technique of Viegas-Pequignot et al. .
The mother was a balanced carrier of a t(3;4)(p12;p15.1)
translocation and the father of a balanced t(5;10)(p12;p13) translocation. The
propositus had a 46, XY, t(3;4)(p12;p15.1)mat, -10, + der10t(5;10)(p12p13)pat.
karyotype in RHG and RTBG banded studies from peripheral blood cultures (Fig.
8). Thus, the patient has a dup(5)(p12 -> 5pter) and del(10)(p13 10pter). In
the mother's family we found a third translocation t(15;21) (q26.2;q21), which
was published by Raoul et al. . The pedigree shows the segregation of
each of 3 translocations (Fig. 4). Individuals V-4 and V-5 had prenatal
diagnosis in another laboratory. It is reported that these 2 patients with
del(5p) were eliminated by abortion.
The pecularity of this case is related to the extremely small chance
of the mating of 2 individuals with different translocations and the occurrence
of another, different translocation in the same family.
Table I summarizes the effect of dup(5p) and del(10p) on the
phenotype of the propositus. No epilepsy was found in the 2 other syndromes.
Abnormal karyotypes disclosed at birth are nearly always the least
unfavorable that can result from the parental translocation with the minimum
loss or gain of chromosomal material [Jalbert et al., 1980). Figure 4 shows the
(5;10) translocation leading to alternate or adjacent-1 segregation carriers.
The adjacent-1 leads to cri du chat syndrome, caused by der5t(5;10), or to a
der10t(5;10) syndrome. In our pedigree, 6 patients (IV-27, IV-35, IV-37, V-3,
V-4, V-5) are der5t(5;10) carriers, and only one, the propositus, is a
der10t(5;10) carrier. This can be due to translocation involving regions of the
genome so important that their imbalance is highly lethal. Studies of the
liveborn offspring of balanced translocation carriers have shown that
predictions can be made for the mode of segregation leading to chromosomal
imbalance [Jalbert et al., 1980]. The reciprocal translocations found in the
family reported here were expected to segregate in different modes according to
the chromosomes and breakpoints involved (Table II). Alternate segregation
results in normal or balanced gametes, whereas imbalances are produced by the
adjacent-I, the adjacent-2, and the 3:1 type of disjunction. The adjacent-2 and
the 3:1 lead to lethal combinations, which are expected to drastically reduce
the fertility of double translocation carriers. In the patient's mother, the
adjacent-1 type of segregation of the (3;4) translocation also leads to lethal
combinations. It is remarkable that no history of stillbirth or spontaneous
abortion has been observed in the propositus mother. Only 8 possibilities of
segregation lead to a viable fetus. As shown in Table II, the theoretical
probability of the couple having a phenotypically normal child would be 1:2,
and a genotypically normal child would be 1:8.
Table I. - A Comparison of Clinical Manifestations Found in
dup(5p), del(10p), and our Propositus
|Life span||N||f||20 Months
|High and flat forehead||+||+||+
|Flat nasal bridge||+||+||+
|Highly arched palate||-||+||+
Table II - Punnet square showing gamete possibilities in
mating of a (3;4) balanced translocation carrier and a (5;10) balanced
translocation carrier, respectively.
|Chromosomes 3 and 4 Disjunction
|Alternate||Adjacent 1||Adjacent 2
| 3,4 ||der3,der4 ||3,der4 ||4,der3
|Chromosomes 5 and 10 Disjunction||Alternate ||5,10||Normal ||der3,der4
||der4 ||der3 ||3,der3,-4 ||4,der4,-3
der5,der10||der4 der5,der10||der3 der5,der10||3,der3,-4
der5||der3 der5||3,der3,-4 der5|| 4,der4,-3 der5
der10||der3 der10||3,der3,-4 der10||4,der4,-3 der10
1O,-5||der4 10,der10,-5||der3 10,der10,-5||3,der3,-4
10,der 1O,-5||4,der4,-3 10,der 1O,-5
5,der5,-10||der4 5,der5,-10||der3 5,der5,-10||3,der3,-4