Trisomies of Chromosome No. 8

J. Lejeune and Marie-Odile Rethoré

Nobel 23 (1973) Chromosome identification


Sommaire

Haut

The Full Trisomy 8

The full trisomy for chromosome 8 has been established clinically [1] and the first demonstration by chromatid fine structure analysis was given by de Grouchy et al. [2].

Recently we have reviewed 5 cases of 8-trisomy, all of them identified in our laboratory by heat controlled denaturation [3].

The full syndrome, exemplified in fig. 1, can be summarised as a general dysmorphy of the bones including koilosterny and 13 ribs, abnormalities of vertebrae and of iliac bones, brachymesophalangy, syndactyly and club foot with limitation of movements of most of the joints.

In contrast, the head is macrocephalic with a eumorphic face. On the ears there is an irregular helix and an excess of the anthelix is seen. The mental deficiency is marked but probably less profound than in 21 trisomy.

The dermatoglyphics shows an upward direction of distal flexion crease, ending between the second and the third digits and all the creases are deep, with little dimples giving an "aspect capitonné". The axial triradius is elevated, the ridges of the distal part of the palm have a cubital orientation (low index of transversality) and there is an excess of arches.

The new trisomy syndrome is thus clinically easily recognized and can be diagnosed firmly by mere inspection and secondarily confirmed by the denaturation technique.

Haut

Trisomy for Distal Part of Long Arm of Chromosome 8

The particular syndrome was first described in two brothers, mildly mentally retarded. Both of them had 47 chromosomes, the extra one being roughly of the size of a G.

According to the old techniques, both parents exhibited a normal karyotype. With denaturation, the mother showed a dark segment on the end of the long arm of No. 8 and one of her No. 22 was replaced by an acrocentric, the long arms of which were rather pale. Hence this small acrocentric consisted of the end part of long arm of No. 8 translocated on the centromere of 22. The long arm of 22 was found at the end of the rearranged 8.

The two boys were trisomics for the distal part of chromosome 8 [4].

A very similar translocation was found recently by Dr Prieur in another family, apparently unrelated, in which a boy (fig. 2) had 47 chromosomes with the same extra pseudo-G, and the father had the 22-8 balanced translocation (fig. 4C).

From these 3 cases we can describe the disease as a mildly dysmorphic syndrome affecting the sternum, the vertebrae, the iliac bones, the digits and the toes as in trisomy 8 but to a milder extent and with no involvement of the articulation and with normal ribs. Two of the boys were operated for ectopic testis.

The head is also macrocephalic and the mental retardation is mild (IQ in the order of 70). Dermatoglyphics shows normal creases but an elevated end of the distal flexion crease and elevation of the axial triradius.

Haut

Trisomy for Short Arm and Middle Part of Long Arm of No. 8

In one case, analysed by Dr Rethoré, we have observed 47 chromosomes, with the extra element being recognized as a No. 8 lacking the terminal part of its long arm (fig. 4B).

This young girl is microcephalic with hypertelorism and has a large broad nose. She has 13 ribs, abnormality of the twelfth vertebra and of the sacrum, and narrowed iliac bones. There is limitation of joint mobility and a club foot (fig. 3).

The creases are 'capitonnés' on the feet but normal on the hands. The ridges of the palms have a cubital orientation (low index of transversality).

It is obviously impossible to designate a new entity based on only one case, but apparently this girl exhibits some of the stigmata of trisomy 8 and, precisely, those which are not found in the trisomy for the end of the long arm. With the increasing amount of similar data, it seems possible that mapping of the phenotypic effects of various chromosomal segments may commence in the not-too-distant future.


Fig. 1. Trisomy 8. Fig. 2. Trisomy for the distal part of long arm of chromosome 8 (trisomy 8q ter). Fig. 3. Trisomy for the short arm and the proximal part of long arm of chromosome 8 (trisomy 8q -)


Fig. 4. (A) Full trisomy 8 ; (B) Trisomy 8q- ; (C) Trisomy 8q ter by 22-8 translocation

Table 1
Full trisomy No. 8Trisomy for the end part of long arm of No. 8Trisomy for short arm and proximal part of long arm of No. 8
Phenotype
Short neck+-+
Koilosternia+++
13 ribs+-+
Abnormal vertebrae+++
Narrow pelvis+++
Brachymesophalangia++-
Symphalangia++-
Club foot+-+
Joint stiffness+-+
Macrocephaly++Microcephaly
Dermatoglyphics
Deep creases "plis capltonnes"+-+
Distal crease ending in 11++-
Elevated axial triradius++-
Low index of transversality+-+
Excess of arches+-+

Haut

Discussion

Haut

Gropp:

It has proved to be very useful for clinical doctors to have a common name for a syndrome, such as "cri du chat" syndrome. Could you propose common names for trisomy 8, and the partial trisomy 8-syndromes?

Haut

Lejeune:

Unfortunately not. To propose a useful name we need a main symptom which is quite pathognomonic. Maybe with an accumulation of new cases the clinical picture will clarify sufficiently to permit such a representative denomination.

Haut

Lindsten:

Your finding of creases in the hands and feet is of interest in relation to the report by Penrose of specific dermatoglyphic features in one subject with trisomy 8. Do you have any information on the dermatoglyphic pattern in your cases with different abnormalities of chromosome 8?

Haut

Lejeune:

Yes, and they are quite typical in each syndrome:

Trisomy 8 (full chromosome): Axial triradius elevated. Low index of transversality of ridges. "plis capitonnés", with the distal flexion crease ending betwen II and III (deeply engraved palmar creases); brachymesophalangy and symphalangy arches on fingers.

Trisomy 8q terminal (trisomy for the end portion of the long arm of No. 8): Axial triradius elevated; distal flexion crease ending between II and III; brachymesophalangy; index of transversality normal; no "plis capitonnés".

Trisomy 8 q (trisomy for short arm, centromere and two-thirds of long arm of No. 8): Index of transversality very low; "plis capitonnés"; excess of arches.


Haut

References

1. Lejeune, J, Dutrillaux, B, Rethoré, M-O, Berger, R, Debray, H, Veron, P, Gorce, F & Grossiord, A, Ann génét 12 (1969) 28.

2. de Grouchy, J, Turleau, C & Leonard, C, Ann génét 14 (1971) 69.

3. Dutrillaux, B & Lejeune, J, Compt rend acad sci 272 (1971) 2638.

4. Lejeune, J, Rethoré, M-O, Dutrillaux, B & Martin, G, Exptl cell res 74 (1972) 293.