Isolated trisomy 7q21.2-31.31 resulting from a complex familial rearrangement involving chromosomes 7, 9 and 10
- Jörg Weimer†1Email author,
- Simone Heidemann†2,
- Constantin S von Kaisenberg1, 3,
- Werner Grote2,
- Norbert Arnold1,
- Susanne Bens2 and
- Almuth Caliebe2
© Weimer et al; licensee BioMed Central Ltd. 2011
Received: 23 November 2011
Accepted: 5 December 2011
Published: 5 December 2011
Genotype-phenotype correlations for chromosomal imbalances are often limited by overlapping effects of partial trisomy and monosomy resulting from unbalanced translocations and by poor resolution of banding analysis for breakpoint designation. Here we report the clinical features of isolated partial trisomy 7q21.2 to 7q31.31 without overlapping phenotypic effects of partial monosomy in an 8 years old girl. The breakpoints of the unbalanced rearranged chromosome 7 could be defined precisely by array-CGH and a further imbalance could be excluded. The breakpoints of the balanced rearranged chromosomes 9 and 10 were identified by microdissection of fluorescence labelled derivative chromosomes 9 and 10.
The proband's mother showed a complex balanced translocation t(9;10)(p13;q23) with insertion of 7q21.2-31.31 at the translocation breakpoint at 9p13. The daughter inherited the rearranged chromosomes 9 and 10 but the normal chromosome 7 from her mother, resulting in partial trisomy 7q21.2 to 7q31.31. The phenotype of the patient consisted of marked developmental retardation, facial dysmorphism, short stature, strabism, and hyperextensible metacarpophalangeal joints.
For better understanding of genotype-phenotype correlation a new classification of 7q duplications which will be based on findings of molecular karyotyping is needed. Therefore, the description of well-defined patients is valuable. This case shows that FISH-microdissection is of great benefit for precise breakpoint designation in balanced rearrangements.
Keywordschromosome microdissection array-CGH developmental delay hypotonia speech-delay short stature epicanthus partial trisomy 7q21.2-7q31.31
Phenotypic reports of chromosomal imbalances are an important source for genetic counselling especially in prenatal diagnosis. Chromosomal imbalances arise de novo or as the result of a familial rearrangement. The most common familial rearrangements are translocations. In case of an unbalanced segregation in an offspring the resulting imbalances consist of a combination of partial trisomy and partial monosomy. In most of the cases it is impossible to exactly relate the phenotypic consequences of an unbalanced translocation to either the underlying partial trisomy or the partial monosomy. Therefore many case reports are of limited value for genetic counselling because the phenotypic effects of trisomy and monosomy overlap . Another difficulty in the description of phenotypic consequences of a certain chromosomal imbalance is the breakpoint designation. The precise description of the breakpoint is important for the genotype-phenotype correlation. In solely cytogenetically investigated patients, breakpoint designation remains doubtful due to the limited resolution of chromosome banding techniques. In recent years comparative genomic hybridisation (CGH) such as array-CGH has overcome many of the limitations of classical chromosomal banding analysis and can estimate the breakpoints with an accuracy of some kb. However, breakpoint designation by CGH and Array-CGH is restricted to unbalanced rearrangements. In case of balanced rearrangements or combinations of balanced and unbalanced rearrangements as in the present case further molecular cytogenetic techniques have to be combined with array CGH such as microdissection and Fluorescence-in-situ-hybridisation (FISH).
Methods and Results
Because of the complex maternal rearrangement amniocentesis was performed in a subsequent pregnancy revealing a balanced complex translocation in a male fetus. The boy was born at term with normal measurements (length 56 cm (+2 SD), weight 3020 g (-1.7 SD)). His motor development was normal. He started walking at the age of 11 months. At the age of 5 10/12 years length was 121 cm (0.74 SD). He attended preschool timely.
There are many publications on partial trisomies in 7q. In most cases the duplication resulted from a familial translocation involving the long arm of chromosome 7 and another chromosome leading to partial trisomy/monosomy 7 and partial trisomy/monosomy of the translocation partner, respectively [3–9]. About 19 patients with isolated trisomy 7 involving various regions of 7q have been described [10, 11]. The phenotype varies according to the region which is duplicated and the size of the duplication. In an attempt to correlate the karyotype with the phenotype, patients with partial trisomy 7 have been divided into groups. Novales and co-workers suggested three groups . Patients with a duplication 7q21 or q22 to 7q31 belong to group 1. The phenotype includes facial dysmorphism (frontal bossing, narrow palpebral fissures, epicanthus, and hypertelorism), strabism, hypotonia, and developmental delay. Group 2 includes patients with duplication 7q31 to 7qter. The phenotype is characterised by low birth weight, large fontanel, facial dysmorphism (narrow palpebral fissures, hypertelorism, small nose, low-set and malformed ears, microretrognathia), cleft palate, developmental delay, skeletal anomalies, and a reduced life expectancy. Group 3 is defined by a duplication of 7q32 to 7qter. These patients show low birth weight, facial dysmorphism (low-set ears, small nose, and hypotonia), kyphoscoliosis, skeletal anomalies, hypotonia and developmental delay. Courtens et al. described group 4 with a duplication involving 7q21 or q22 to 7qter . One has to bear in mind that the clinical descriptions are mainly based on patients assessed by chromosome banding analyses.
The patient described herein has isolated partial trisomy 7q21.2 to 7q31.31 without additional chromosomal imbalances as confirmed by array-CGH. She therefore fits best into group 1 and displays the typical symptoms, namely low birth weight, global developmental delay with marked hypotonia in infancy, marked delay in speech development, mild short stature, normal head circumference, strabism and mild unspecific facial dysmorphism. Our patient can be best compared to the patients described by Humphreys et al. and Romain et al. [13, 14]. Low birth weight was also a symptom in the patients described by Grace et al. and Berger et al. [15, 16]. In contrast to other descriptions the palpebral fissures were of normal size.
To enable a future new classification of duplications in 7q which will be based on findings of molecular karyotyping the description of well-defined patients is valuable. Furthermore, this case shows that FISH-microdissection is of great benefit for breakpoint designation in cases of balanced and/or complex rearrangements.
Written informed consent was obtained from the parents of the patient for publication of this case report and all images.
We thank Professor Dr. med. Reiner Siebert, Institute of Human Genetics, Christian-Albrechts-University of Kiel, University Hospital Schleswig-Holstein, Campus Kiel, for the ongoing support of this study.
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