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 9½-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.

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.