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Indian Pediatr 2013;50: 157-158 |
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Diagnostic Dilemma in Overlapping Congenital
Syndromes
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*Frenny Sheth and Madhumita Kaul
*FRIGE’s Institute of Human Genetics, FRIGE House
Satellite, Ahmedabad-380015, India.
Email:
[email protected]
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Chromosomal or segmental aneusomy are an important cause of
congenital malformations, emphasizing the need for
cytogenetic evaluation. Many congenital malformations,
especially those with multi-systemic anomalies present
overlapping phenotypic features that could partly be
attributed to multiple gene deregulations. Moreover, the
expressivity of phenotypic features of a particular syndrome
could vary extensively among the patients and hence, request
for a specific test becomes difficult as observed in the
present case.
A 9˝-months-old, phenotypically female
child was born at term to non-consanguineous parents with a
birth weight of 2700g. She presented with developmental
delay and showed microcephaly (<2SD deviation), hypotonia,
truncal ataxia, depressed nasal bridge with long philtrum,
mild frontal bossing and hepatomegaly of 2.5 cm.
Echocardiogram revealed large Ventricular Septal Defect with
pulmonary arterial hypertension and a small patent foramen
ovale. There was no submucus cleft palate. Developmental
assessment suggested a moderate delay with motor development
of 4.7 months and mental development of 5.5 months. Other
investigations such as TORCH, serum calcium and parathyroid
hormone levels were within the normal range. There was no
ultrasonographic evidence of renal, urethral and bladder
anomaly. Based on these constellations of clinical symptoms
and signs, a clinical assessment of 22q11.2 deletion
syndrome encompassing DiGeorge syndrome (DGS) was made.
DGS is a common congenital disorder,
where pathogenesis has been linked with chromosome 22q11.2
abnormalities [1-3]. Fluorescence in situ
hybridization (FISH) analysis was carried out using TUPLE
region probe (from Kreatech Diagnostics, Netherland) on
metaphase and interphase cells. Presence of two intact
signals on chromosome 22 ruled out 22q11.2 deletion. Thus,
chromosomal analysis was carried out using the GTG-banding
technique and the patient was found to be tetrasomy for sex
chromosome-X i.e. 48,XXXX.
The degree of clinical presentation for
tetrasomy X is highly variable, and tend to have distinctive
facial features that include - epicanthal folds, flat nasal
bridges, midface hypoplasia, cleft or high arched palates,
hypotonia and cardiovascular defects as well as
developmental and motor delays [4]. All the above mentioned
features can also be observed in cases with 22q deletions as
seen in the present study and hence, if only FISH study was
processed, tetrasomy X would not have been diagnosed.
This demonstrate that FISH can detect
only targeted anomalies whereas conventional cytogenetic can
give information about the whole genome alterations and
hence be a guide for further diagnostic modalities if
required.
Acknowledgments: Dr
Akinde Ralph, Mr Adeteye Olawale and Dr Jayesh Sheth for
intellectual discussions. The work is partly supported by
Department of Biotechnology, India.
References
1. McDonald-McGinn DM, Goldmuntz E,
Sullivan K, Eicher P, Gerdes M, Moss E, et al. The
22q11.2 Deletion: Screening, Diagnostic Workup, and Outcome
of Results; Report on 181 Patient. Genet Test. 1997;1:99-108
2. Bartsch O, Nemecková M, Kocárek E,
Wagner A, Puchmajerová A, Poppe M, et al. DiGeorge/velocardiofacial
syndrome: FISH studies of chromosomes 22q11 and 10p14, and
clinical reports on the proximal 22q11 deletion. Amer J Med
Genet Part A. 2003;117:1–5.
3. Tabith Júnior A, Genaro KF, Trindade
Júnior AS. Velocardiofacial syndrome with facial and pinna
asymmetries. Braz J Med Biol Res. 1996;29:1445-7.
4. Schinzel A. Catalogue of Unbalance Chromosome
Aberrations in Man. 2nd Edition. New York: Wlater de Gruyter;
2001.p. 933.
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