A. H. Khan ( Department of Pathology, The Aga Khan University, Karachi. )
Z. Khilji ( Department of Pathology, The Aga Khan University, Karachi. )
M. Azim ( Department of Pathology, The Aga Khan University, Karachi. )
M. Khurshid ( Department of Pathology, The Aga Khan University, Karachi. )
Chromosomal aberrations are one of the most frequent causes of multiple congenital malformations and mental retardation. Trisomy 21, 18 and 13 are the most common varieties of autosomal trisomy recognized at birth; most of the others lead to spontaneous abortions in the first trimester’. Full trisomy 9 is rare in live born infants, but trisomy 9 mosaic ism has been reported and compatible with life. Unlike trisomy 21, 18 and 13, the range of clinical manifestation has not been well described, especially with respect to mental status1,2.
A 13 month old female child presented with a suspicion of Down’s syndrome, in our cytogenetic laboratory. The baby was born in 1999, to a healthy consanguineous marriage with no history of similar child in the family. She was the youngest child from a family of 4, with 2 brothers and sister. All of them were normal and healthy. Delivery was normal at full term, birth weight was 2 kg, length 45 cm and occipitofrontal circumference (OFC)
32.5 cm. At birth she had multiple abnormalities related to craniofacial skeleton, facial dysmorphism, short stature and slow growth (Table ).
At the time of presentation weight was 7.8 kg, length 67 cm and OFC was 42 cms, all below the 5th centile. Developmental milestones were at a 7-month level.
The physical features suggestive of trisomy were first noticed at 4 months of age but a conclusive diagnosis could not be ascertained for her delayed milestone till the time her chromosomal analysis was performed at our laboratory.
Chromosomal analysis was performed by inoculating peripheral blood cells into growth media and culturing for a short period of time allowing a sufficient number of cell mitoses for harvest and analysis. Phytohemagglutinin was used to stimulate mitoses. Colcemid was used to arrest mitoses in the metaphase stage of cell division by inhibiting spindle fibre formation. Metaphase lymphocytes were then swelled in a hypotonic solution, fixed, mounted on slides and stained. It was then analyzed on Cytovision software version 4.1 from Applied Imaging (UK). Fifty cells were counted; 96% of the cells (Figure ).
This case of trisomy 9 is the first to be diagnosed in our clinical genetics department. The purpose of this report is to highlight the features for the diagnosis of a rare trisomy and to emphasize the importance of carrying out a chromosomal analysis in such cases for confirmation of diagnosis. The clinical variability seen in our case could be the result of a variable degree of mosaicism and differences in the location of tissue involved1.
Two forms so far have been recognized; Trisomy 9p and Trisomy 9 mosaic1,2. Both are distinct entities in infants. In trisomy 9p part or all of the short arm (p) of chromosome 9 is present 3 times (trisomy). In some cases, a trisomic segment of the long arm (q) of chromosome 9 may also be present. The symptoms of the disorder are unusually similar among affected infants despite differing lengths of the duplicated segment and are thought to be related to extra chromosomal material on the distal portion of the short arm (9p).
In trisomy 9 mosaicism, the severity of the symptoms and survival may depend on the percentage of cells with the extra chromosome, with most of the patients dying before the age of 4 months in complete trisomy3.
Characteristic feature include delayed growth of the fetus, congenital heart defects, facial abnormalities, m icrocephaly. kidney and/or genital abnormalities, skeletal abnormalities, and/or malformation of the brain, usually including a dilated fourth ventricle and malformed cerebellum. The posterior fossa malformation closely resembles the description of Dandy-Walker malformation4.
Affected infants may also experience growth retardation and a significant delay in the acquistion of language and communication skills. Various structural heart defects have also been reported, demonstrating conal and valvular anomalies associated with ventricular septal defect4.
Most cases are the result of a spontaneous (de novo) genetic change early in embryonic development that occurs for unknown reasons. In some cases of Chromosome 9, Trisomy 9p occurs because of balanced chromosomal rearrangements between two chromosomes of one of the parents; chromosômal analysis is necessary for definite diagnosis4. ln addition to karyotyping results, sonographic findings of mosaic or non-mosaic trisomy 9 are well documented. The findings vary from intrauterine growth retardation, Dandy-Walker malformation and various degree of heart defects. In such cases, prenatal diagnosis allows the parents to make an informed decision regarding intervention. Amniotic cell culture provides useful information in cases of mosaicism as compared to fetal cord blood cytogenic analysis, which may be normal5. Fluorescence in situ hybridization (FISH) is a powerful new technique that allows numerical chromosome aberrations (aneuploidy) to be detected in interphase cells5.
I would like to thank Dr. Nazir Ahmed Malik at PNS Shifa Hospital and Dr. G. N. Kakepoto for their support in writing of this manuscript.
1.Saura R, Traore W, Tame L et al. Prenatal Diagnosis of trisomy 9. Six cases and a review of the literature. Prenat. Diagn., 1995,15:609-14.
2.Stoll C, Chognot D, HaIb A et al. Tnsomy 9 mosaicism in two girls with multiple congenital malformations and mental retardation. J. Med. Genet., 1992,30:433-35.
3.Tarani. L, Colloridi-F, Raguso-G et al. Trisomy 9 mosaicism syndrome A case report with review of the literature. Ann. Genet,, 1994,37:14-20.
4.Mermo-A, De-Perdigo-A, Nombalais-F et al Prenatal diagnosis of trisomy 9 mosaisicm: two new cases. Prenat. Diagn., 1993;13:1001-1007.
5.Van-den-Berg_C, Rarnlakhan-SK. Van-Opstal-D, Brandenburg-H, Halley.DJ, Los-Fi. Prenatal diagnosis of trisomy 9: cytogenetic, fish and DNA studies. 1997;17: 933-940.