Phenotypic correlations in a patient with ring chromosome 22 Case Report

Ring chromosome 22, a rare cytogenetic anomaly, has been described in over 60 cases in the medical literature. The aim of this report was to present a case carrying ring chromosome 22, and her family. It is a case report of a patient presented at Medical Faculty of Çukurova University in Turkey. An 8-year-old girl with ring chromosome 22 and her family were evaluated cytogenetically and clinically. A chromosome analysis of the proband revealed a de novo 46,XX,r(22)(p11.2;q13) karyotype. Our subject demonstrated the prominent features of this syndrome including profound mental retardation, language impairment, dysmorphic features, lack of speech, hyperactivity, and behavioral disorders. There is lack of consistency between the physical abnormalities that we observed in our subject and those observed for such patients in the literature. The wide range of manifestations observed in patients with this cytogenetic alteration is probably due to size differences in the deleted region.


Introduction
Ring chromosomes are formed by breakage in both arms of a chromosome with fusion of the points of fracture and loss of the distal fragments. Ring chromosome 22, a rare cytogenetic anomaly, was firstly described by Weleber et al. in 1968. [1] Since then, approximately 60 cases have been described in the medical literature.
Its most consistent findings are overall developmental delay with severe speech disability, growth retardation with frequently associated microcephaly, hypotonia, and dysmorphic traits such as epicanthus, mental retardation, normally placed but large and dysplastic ears, long face, thick eyebrows, 2-3 toe syndactyly, long eyelashes with full eyebrows, and occasionally high arched palate, dental malocclusion, and mild hypertelorism. [1,2] Second and third toe syndactyly, unsteady gait, hyperactivity, aggressive behavior, autistic disorders, seizures, and abnormal EEG1 have also been reported. [3] These manifestations suggest that the central nervous system development of the affected patients is also altered. In addition to ring formation, deletion of the 22q13 region of chromosome 22 represents a recognizable cytogenetic microdeletion syndrome. There are currently 23 such cases published in literature, [4,5] and the clinical characteristics present in all patients include severely retarded speech, moderate mental retardation, and hypotonia. The clinical variations observed can result from the occurrence of different sized deletions. Molecular studies of the region [5] have revealed both the size of the critical region and the function of some of its genes. [6] We report the cytogenetic analysis of ring chromosome 22 in a girl investigated for mental retardation, minor dysmorphic features, severe speech delay, hyperactivity, and aggressive behaviors.

Case Report
The proband, an 8-year-old girl, was the second child born to healthy non-consanguineous parents, after normal gestation. There was no family history of intellectual sation handicap or mental illness. She was diagnosed with mental retardation at 3 years of age.
She was referred to the Child Disease Department For each family member studied, including proband, 20 metaphases was analyzed. The father (40 years) and mother (35 years) of the proband were healthy.
The mother had two pregnancies that resulted in the delivery of healthy child. After cytogenetic analysis of the proband, cytogenetic analyses of both the parents and the sister of the proband were also done. Both mother and father showed normal female karyotpe (46,XX) and male karyotype (46,XY), respectively. The karyotype of her sister was 46,XX. So, this chromosome alteration of the proband was considered as 'de novo'.

Discussion
Due to its rare cytogenetic finding, the exact incidence of ring chromosome 22 is unknown. Its most consistent clinical findings are overall developmental delay with severe speech disability, growth retardation with frequently associated microcephaly, hypotonia, and dysmorphic traits such as epicanthus, mental retardation, normally placed but large and dysplastic ears, long face, thick eyebrows, 2-3 toe syndactyly, long eyelashes with full eyebrows, and occasionally high arched palate, dental malocclusion, and mild hypertelorism. [1,2] Second and third toe syndactyly, unsteady gait, hyperactivity, aggressive behavior, autistic disorders, and seizures or abnormal EEG1 have also been reported. [3] The other clinical  severe in the area of expressive language, hypotonia, minor dysmorphic featurs including dolichocephaly, epicanthic folds, syndactyly between toes 2 and 3, and behaviors that overlap with those in the autistic spectrum disorder must be mentioned. [7] For all cases, either 22q13 deletion syndrome cases or r (22)