OBJECTIVES: Rett syndrome (RTT) is a neurodevelopmental disorder that affects girls almost exclusively. This study aims to identify the genetic alterations of RTT by using the conventional cytogenetic techniques Trypsin G- banding with Mecp2 genotype, and to estimate the role of association in Dopamine and serotonin levels as a consequence of neurotransmitters. METHODS: A total of 13 RTT patients were evaluated based on the Diagnostic and statistical manual of the American psychiatric association (DSM-IV). Human Peripheral blood Leukocyte culture for chromosomal analysis was screened, the genotypic polymorphism was analysed using the PCR-RFLP methods and Plasma GABA analysis and serotonin levels were also measured. RESULTS: Abnormal karyotypes were found in the chromosomes 17, 21, 22 and X. C to T transition in exon 2 of Mecp2 resulting in R106W amino acid substitution. 316 C to T transition nucleotide changes and R106W amino acid changes were observed in 7 subjects, 824delcins11 were seen in 4 subjects, 916 C to T nucleotide and R294W amino acid change in 2 patient each. Higher frequency of XCI was observed in subjects with severe RTT (Max. 95.5%). Among the neurotransmitter levels, elevated level of Dopamine and serotonin levels (p>-001) was measured. CONCLUSIONS: In conclusion, in this pilot study, we observed that the identification of cytogenetic abnormalities is not only important for providing a cause for the RTT in a single individual of twins and is also critical for accurate counseling regarding recurrence risks to parents and family members. Although these findings should interpret with caution, and larger, more standardized studies are warranted. Key Words: Rett syndrome, MECP2 mutation, neurotransmitters, chromosomal analysis