Significance of molecular karyotyping for diagnosis specification in case of cytogenetically detected chromosomal aberrations

Introduction: Patients with chromosomal disorders are characterized by wide clinical polymorphism, which reasons are quite varied and not always clear. For geneticist it is difficult to make an accurate diagnose because of symptoms variety in a patient. Conventional cytogenetic analysis is not always effective in identifying the genetic cause of the disease. The quality and accuracy of diagnosis is significantly increased with the use of high-resolution molecular karyotyping. Aim: The work was aimed to establish the boundaries of chromosomal mutation that led to the formation of a ring chromosome 22 and to analyze genotype-phenotype correlations in a patient with developmental delay and congenital malformations. Materials and methods: Ring chromosome 22 was revealed using the conventional cytogenetic analysis. Microdeletions 22q13.32-q13.33 and 3q13.31 were detected by aCGH (860K, Agilent Technologies). Results: The patient presented the symptoms of both syndromes (microdeletion 3q13.31 and 22q13.32-q13.33 (Phelan-McDermid syndrome): delayed psychomotor development and speech, signs of autism, frontal bossing, epicanthus, ear anomalies. Clinical features specific for 3q13.31 microdeletion were presented by attention deficit hyperactivity disorder, short and smooth filter, a thin upper lip, ventriculomegaly. Clinical features specific for 22q13.32-q13.33 microdeletion were presented by aggression, tall stature, microcephaly, bulbous nose, sacral dimple, CNS malformations, seizures, sleep disorders, heart defects. Features previously not described in any patient with either 3q13.31 or 22q13.32-q13.33 microdeletion include sloping occiput, straight eyebrows, up-slanting palpebral fissure, telekanthus, wide and depressed nasal bridge, wide umbilical ring, brachydactyly of I and V fingers of hands and all toes, thickened distal phalanx of first fingers of hands and feet, flat-valgus foot. Conclusions: The analysis shows the significance of the additional high-resolution molecular karyotyping for patients with cytogenetically visualized chromosomal abnormality in the presence of atypical clinical signs for such pathology.

кольцевая хромосома 22, синдром Фелан, МакДермид, синдром микроделеции 3q13.31, матричная сравнительная геномная гибридизация, ring chromosome 22, Phelan, McDermid syndrome, 3q13.31 deletion syndrome, aCGH

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