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Journal Français d'Ophtalmologie
Volume 32, n° 8
pages 533-539 (octobre 2009)
Doi : 10.1016/j.jfo.2009.06.004
Received : 29 April 2009 ;  accepted : 16 June 2009
Partial mosaic trisomy 5: A new case report with ocular involvement
Atteintes oculaires chez un enfant atteint d’une trisomie 5 partielle en mosaïque

Z. Schlegel a, , A. Valent b, A. Hirsch a
a Ophthalmology Department, Gonesse Hospital, Gonesse, France 
b Histocytopathology Unit, Gustave Roussy Institute, Villejuif, France 

Corresponding author. Service d’ophtalmologie, Centre hospitalier de Gonesse, 25, rue Pierre de Theilley, BP 30071, 95503 Gonesse cedex, France.

We describe a new case of a male patient with a small marker chromosome present as 80% mosaic, derived from chromosome 5 with presence of posterior iridolenticular synechia, high hyperopia, epicanthic folds, hypertelorism, moderate developmental delay with lack of speech, macrocephaly, and subtle dysmorphic features including micrognathia, slightly rotated ears, and polydactyly. The karyotype of our patient was as follows: 46, XY/47, XY +mar, characterized by FISH (fluorescence in situ hybridization) using the chromosome five painting probe. Ocular involvement in trisomic 5 subjects is a very rare event. To our knowledge, only two cases have been described to date. The present case contributes to the description of the ocular presentation and the distinct clinical phenotype of de novo partial trisomy 5 syndrome.

The full text of this article is available in PDF format.

Nous décrivons un nouveau cas de sexe masculin avec présence de mosaïcisme à 80 % de petit marqueur dérivé du chromosome 5, présentant des synéchies postérieures iridolenticulaires, une hypermétropie forte, des replis épicanthiques avec hypertélorisme, un retard de développement modéré avec absence de langage, une macrocéphalie et quelques subtiles dysmorphies caractéristiques comme une micrognatie, les oreilles légèrement tournées et des doigts surnuméraires. Le caryotype du patient (46, XY/47, XY+mar) a été caractérisé par la méthode FISH (fluorescence in situ hybridization), en utilisant une sonde de coloration du chromosome 5. L’atteinte oculaire chez les patients porteurs de trisomie 5 est très rare. D’après nos connaissances seulement, deux cas ont été décrits jusqu’à présent. Le cas actuel contribue à la description de la présentation oculaire en plus de phénotype clinique indéniable du syndrome de de novo trisomie partielle 5.

The full text of this article is available in PDF format.

Keywords : Trisomy 5, Mosaic, Chromosome 5, Ocular involvement

Mots clés : Trisomie, Mosaïque, Chromosome 5, Atteintes oculaires


Trisomy of the short arm of chromosome 5 is a clinically discernible but very infrequent syndrome with characteristic features, considered by Stoll et al. [1] as the reverse type of cri-du-chat syndrome. Lejeune et al. [2] first described this chromosomal abnormality in 1964; later a description was provided by Gustavson et al. [3] in 1988. The Office of Rare Diseases (ORD) of the National Institutes of Health (NIH) lists chromosome 5 trisomy as a “rare disease”; this means that chromosome 5 trisomy with both its subtypes, 5p and 5q, affects fewer than 200,000 people in the US population. Its incidence and prevalence are difficult to establish. Few reviews or concrete documented cases are available. For the 5p duplication, for example, in 2000 Velagaleti et al. [4] reported more than 40 documented cases and reviewed seven cases dating from 1977 for various regions of the short arm of chromosome 5. In 2006, Douyard et al. [5] reported 14 cases of 5q duplication and reviewed another ten cases of proximal 5q trisomy dating from 1975. We must also consider potentially misdiagnosed or undiagnosed children.

In the clinical description, we distinguish duplication of the short arm, e.g. partial or complete trisomy 5p, from the partial or complete duplication of the long arm of chromosome 5q, whose symptomatology is slightly different. Newborn trisomic 5p infants are noted to have disproportionate growth and dysmorphic craniofacial and other unusual corporal features, psychomotor retardation, and cardiovascular and neurological abnormalities. Table 1 summarizes the phenotypes and associated genotypes for various regions of trisomy 5p [4, 6]. A few cases of mosaic tetrasomy 5p have also been documented in born children [7, 8, 9, 10] and by prenatal diagnosis [11], corresponding to the trisomic presentation. The 5q trisomic children gradually develop severe mental retardation and pathognomonic lack of speech. Physical examination shows typical microcephaly with short stature due to the craniosynostosis and synostosis of many other structures (reverse type of Sotos syndrome) [12], craniofacial, heart, lung, abdomen and genital malformations. Table 2 summarizes the phenotypes and associated genotypes for various regions of trisomy 5q [5].

We report a new patient, a 1-year-old Malagasy boy who presented for an ophthalmologic examination with an anterior segment synechia. The present case describes the distinct clinical picture of the partial trisomy 5 syndrome and its genotype–phenotype correlation. It is a case of de novo rearrangement, with a normal karyotype in both parents. Our patient had shown karyotype 46, XY/47, XY +mar. FISH with different whole chromosome painting probes showed that the small marker chromosome contained the chromosome 5 sequences.

History and clinical observation

We describe a male Malagasy infant with a small supernumerary marker chromosome 5 (sSMC) present in 80% of metaphases. The child was born at 33 weeks gestation after in vitro fertilization and embryo transfer (IVF-ET) to the 37-year-old mother with a history of sterility due to Fallopian tube obstruction. The boy was born as a result of the first successful pregnancy after two unsuccessful IVF-ET attempts with two unrelated and healthy parents.

Ultrasonographic examination showed a failure to thrive beginning in the 4th month of gestation. The main stigmata in neonatal clinical findings was a discrete craniofacial dysmorphism such as macrocephaly, micrognathia, low-set rotated ears with reduced cartilage and depressed nasal bridge (Figure 1), moderated neonatal icterus accompanied by anemia, generalized hypotony, Apgar score 5/10, foramen ovale apertum, and foot polydactyly. Another finding was represented by grade II intraventricular hemorrhage and ventriculomegaly that persisted during the 1st year of life and was confirmed by cerebral ultrasonographic examination and computed topography. Brain magnetic resonance imaging (MRI) showed enlarged lateral ventricles, but the brain stem and cerebellar structures were normal.

Figure 1

Figure 1. 

Frontal view of the patient at the age of 6 months.


In postnatal progression, we observed failure to grow, psychomotor retardation, significantly lower verbal communication, minimal aimed mobility, lower motor coordination and fine motricity, and biventricular hydrocephalus that was subsequently stabilized with no need for surgical correction. Speech, sitting and walking capacities at 14 months were not developed. Bronchial involvement included recurrent respiratory infections, asthmatic attacks and respiratory distress syndrome. The immunologic examination revealed the deficiency of both serum and secretory IgA in the blood and salivary samples (0.03g/l and 0.007g/l, respectively) diagnosed at 4 months of age. Surgery for supernumerary foot digits and later inguinal and umbilical herniation was performed in the early postnatal period. Gastroesophageal reflux was treated medically. The ocular examination showed a large hyperopic composed astigmatism (+9 diopters spherical equivalent), hypertelorism, mongoloid eye slant, epicanthus, and posterior sector iris synechia (Figure 2), without whole lens opacification, congenital glaucomatous changes or posterior segment involvement. The anterior chamber was deep in spite of high hyperopia. The iris sphincter demonstrated minimal rhexis and synechia constituting residual Wachendorf pupillary membrane with discrete and limited polar cataract (Figure 3). We wondered about the rapid regression of alternating esotropic strabismus soon after the first wear of high hyperopic correction, in the range of +7.5 D spherical equivalent, toward the completely orthophoric position.

Figure 2

Figure 2. 

Iridolenticular synechia.


Figure 3

Figure 3. 

Visualization of remnants of Wachendorf pupillary membrane.


Genetic analysis

The first cytogenetic analysis was performed at 18 weeks of pregnancy. The amniotic fluid was submitted to karyotype examination, which demonstrated a duplication of sSMC. The amniotic fluid cells were cultivated and harvested after colcemid treatment. The first analysis showed the 46XY[x]/47XY+mar [x] karyotype. The FISH probes from chromosomes 2, 4, 5, 6, 8 and 10 were used to identify the origin of the marker chromosome. Cytogenetic molecular techniques identified the marker as derived from chromosome 5 with 40% mosaicism and including the chromosomal centromere. The whole amount of the marker was painted by the chromosome 5 painting probe and contained potentially euchromatic material. These results were confirmed at the postnatal age of 6 months. The chromosomal analysis of our subject was performed using his peripheral blood lymphocytes that were routinely cultured. In 10 of 16 metaphases examined, a small marker chromosome was observed at 80% mosaicism. Fluorescence in situ hybridization analysis using whole chromosome painting (Abbott Laboratories, Abbott Park, IL, USA) for chromosome 5 was performed, confirming the earlier results (Figure 4). We performed the second FISH analysis with a fluorescent probe for myelodysplastic syndrome, which covers two different locations on the long arm of chromosome 5 (Kreatech Diagnostics, Amsterdam, The Netherlands). The two color probes hybridized well on both normal copies of chromosome 5 at the 5q31 and 5q33 regions, but no hybridization signal was seen on the small marker chromosome 5. We also hybridized the telomeric probe 5q located at 5q35; again we saw the spots only on both normal copies of chromosome 5 but not on the marker chromosome. We did not hybridize any other probes located on chromosome 5p.

Figure 4

Figure 4. 

Fluorescence in situ hybridization using the human 5 chromosome probe, showing a complete fluorescence of both the normal chromosome 5 and the marker chromosome.


We did not find paternal inheritance or translocation or disomy; both parents had normal karyotypes, indicating that the rearrangement is de novo . Because the patient’s family had moved to another country, it was impossible to obtain material for the array CGH analysis to discover the exact origin of the marker chromosome.


Small supernumerary marker chromosomes are present in about 0.05% of the human population. In approximately 30% of sSMC cases, an abnormal phenotype is observed. The clinical outcome of an sSMC is difficult to predict. Subjects can have different phenotypic consequences because of differences in euchromatic DNA content, different degrees of mosaicism, or parental disomy of the chromosomes homologous to the sSMC [13]. Although monosomy 5p (cri-du-chat syndrome) or trisomy 5p are clinically well-characterized syndromes, variations in their clinical features are observed, depending mainly on chromosomal segment and size involvement. In most of the previously described cases, the trisomy is the result of unbalanced translocations; few cases have been reported as a de novo rearrangement or an isochromosome. Complete (or almost complete) [14, 15, 16] 5p trisomy is fortunately less frequent than partial 5p trisomy. It has been suggested that the severity of the clinical spectrum of trisomy 5p is related to the critical region between 5p10 and p13 [17].

The mosaicism of our proband certainly contributes to a more subtle proportion of the clinical severity but is consistent with already documented trisomy 5p patients [18]. Trisomy 5 mosaicism in amniotic fluid or in chorionic villi samples has been reported as well in a number of cases with normal outcome at birth and without abnormal cell lines in the newborns. In most cases where trisomy is found in chorionic villi but not in amniotic fluid, the outcome is normal, probably because the trisomy 5 cell line starts as an extraembryonic event or is confined to the placenta and the extra chromosome 5 is lost from the fetus in a rescue process [19]. In a like manner, trisomic cell percentage in the amniocytes did not seem to predict pregnancy outcome, which could result in a normal liveborn infant [20]. The different mosaicism ratios could be found in the various tissues (blood, skin fibroblasts, chorionic cytotrophoblasts) and might reflect differences between these tissues in selection pressure on cells with the abnormal chromosome [21]. It is therefore possible that the trisomy 5 mosaicism could be an example of tissue-limited mosaicism with the abnormal cell line surviving in some somatic tissues but not in others, most often in fibroblasts, whereas the karyotype of peripheral blood is normal [22]. On the contrary, in our proband we performed only the analysis of peripheral blood lymphocytes with a diagnostic confirmation of mosaic presentation of trisomy 5, in a different ratio than the previous amniotic sampling, but the skin fibroblast karyotype exploration has not been executed.

In addition to the cases of trisomy 5p described, the literature reports a small number of chromosome 5p tetrasomy cases [7, 8, 9, 10, 11, 23], in different ratios of mosaicism and corresponding viability. There is no report of non-mosaic 5p tetrasomy and the probands share the clinical picture of complete 5p trisomy. The most recent report by Hansen et al . [23] provides information on pigmentary skin disorders combined with neurological deficits. Our FISH hybridization procedure allowed us to assume that the chromosome 5 marker does not contain the 5q material and the clinical phenotype of this patient is more or less similar to the clinical description of patients with duplication of chromosome 5p affecting at least the 5p13 band (compatible for the main stigmata: macrocephaly, craniofacial anomalies, hypotonia, mental retardation, cardiac, central nervous system and intestinal anomalies) [24], e.g. it more closely matches 5p than 5q symptomatology. Our proband presents, for example, macrocephaly instead of microcephaly as well as an absence of craniosynostoses or other dysostoses. A priori a lack of speech, mental and growth retardation and heart septal anomalies are common symptoms possible for trisomy of both arms, as well as some dysmorphic heterogeneity. Recently, de Carvalho contributed a very extensive report on a family with five living members with partial trisomy 5p and six living members with monosomy 5p resulting from an unbalanced translocation (t5;15) located at the 5p13.3-pter segment of the chromosome, sharing the same distal phenotype and genotype with minimal variations in trisomic probands. These individuals ranged in age from 9 to 43 years and showed midface hypoplasia, a low-set hair line, dental malformations, flat feet, abdominal muscular hypoplasia, and premature aging in the adults [25]. While having many common features with 5p trisomy syndrome, in addition to the previously described anomalies, the child presented herein also had polydactyly and a very rare ocular presentation.

To our knowledge, this is the third documented case of an ophthalmologic disorder associated with trisomy 5p syndrome: two cases of atypical Peters anomaly have already been reported [4, 26]. Peters anomaly is characterized by a corneal opacity with variable iridolenticulocorneal adhesions, more often bilateral and associated with deep amblyopia. It is considered an incomplete separation of the lens vesicle from the surface ectoderm in the 4th and 5th weeks of gestation. However, our patient had not developed anterior iridocorneal synechiae, but only the unilateral posterior synechiae forming persistent pupillary membrane with delicate iridorrhexis. This Wachendorf membrane could be an incomplete or partial form of Peters anomaly and suggests anterior chamber cleavage or prosencephalic neurocristopathy disorder. It is well known that minimal anterior segment dysgenesis can progress to congenital dysgenesis glaucoma, but our patient remains free of glaucomatous symptomatology. The fundus examination disclosed a normal disc and macular reflexes were detectable; his iridocorneal angle was open. There was no indication for surgical treatment, as the polar localized opacity out of axis does not seem to cause visual impairment by astigmatogenous anterior lenticonus, and other lens zones remained clear and free from dislocation. These observations suggest that chromosome 5 may contain gene(s) playing a role in anterior segment dysgenesis in which abnormal cleavage of the anterior chamber occurs. In a similar manner, Grosso et al. [16] suspect that the chromosome 5 genes implicated in central nervous system development may explain cerebral dysgenesis in some patients with trisomy 5. We cannot perform another genetic analysis because the patient has been lost to follow-up, but further explorations could try to delineate the critical chromosomal region establishing karyotype–phenotype correlations of ocular presentation.


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