Case reportGirl With Partial Turner Syndrome and Absence Epilepsy
Introduction
The classic phenotype of Turner syndrome includes short stature, ovarian failure, and variable somatic stigmata. It is associated with chromosome X monosomy. However, mosaic and partial deletions or duplications of chromosome X result in different degrees of Turner syndrome [1]. Deletions of the whole short arm of chromosome X in females are associated with short stature, gonadal dysgenesis, and the classic stigmata of Turner syndrome [2].
A minimal deletion of chromosome Xp causes a partial Turner phenotype. Haploinsufficiency of the short-stature homeobox (SHOX) gene causes not only short stature, but also characteristic skeletal features such as short metacarpals, cubitus valgus, Madelung deformity, high-arched palate, and short neck [3], [4]. One isoform, SHOXa, is expressed in the brain [3], and it was speculated that the gene affects functions in nervous-system development [5]. Very small microdeletions of chromosome X, including SHOX gene deletion, are usually diagnosed by means of fluorescent in situ hybridization analysis [3] or microarray-based technologies [6]. However, there should first be a clinical suspicion of a SHOX gene deletion or other small X-chromosomal aberrations, because the routine chromosomal analysis usually does not reveal any abnormalities.
We describe a 16-year-old girl with some stigmata of Turner syndrome, panic attacks, symptomatic typical absence seizures, and a distal Xp22.3 deletion including the SHOX gene, as well as a proximal Xp22.3 duplication.
Section snippets
Case Report
The patient was the first child of healthy, nonconsanguineous, Estonian parents. The family history was negative for congenital anomalies. The patient was born by normal vaginal delivery at term, with a birth weight of 2300 gm (−2.5 standard deviations) and a length of 47 cm (−2 standard deviations). At age 5-6 years, she was referred to a psychologist because of panic attacks and fears. She was treated with psychotherapy.
At age 10 years, epilepsy was first evident. At age 11 years, symptomatic
Results
Routine chromosomal analysis indicated an abnormal chromosome X, with a suspicion of additional material on the short arm. Fluorescent in situ hybridization analysis revealed metaphases with a normal chromosome X and an abnormal X chromosome that carried a deletion of the distal part of Xp22.33 (including the short-stature homeobox gene) and a duplication of Xp22.3 proximal to the deleted segment. Array-multiplex amplifiable probe hybridization methodology, as described elsewhere [6], was used
Discussion
The distal part of the short arm of the chromosome X is particularly desirable to study because of the high frequency of deletions occurring in this region [7]. Females with Xp deletions seldom manifest any abnormalities because of the presence of a normal chromosome X and preferential inactivation of the abnormal chromosome X.
The deletion in our patient involves the Xp22.33 region, which according to the Online Mendelian Inheritance in Man database contains 11 genes. Six of these do not
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