RESUMEN
Tetrasomy 21 is a rare occurrence. Only 14 cases have been reported in the literature, 8 of which are partial tetrasomy cases and 6 which are complete tetrasomy cases. Of the incidences, no proband with true complete tetrasomy 21 has survived the neonatal period. We report complete mosaic tetrasomy 21 in a female infant with the typical Down syndrome phenotype, including Hirschsprung's disease and atrioventricular (AV) canal defect. This is in contrast to cases of partial tetrasomy 21, which often have an atypical trisomy 21 presentation and multiple nonspecific traits, including short stature, microcephaly, and developmental delays. This case demonstrates the difference in clinical presentation between the partial and complete subtype of tetrasomy 21 and provides the first postnatal clinical picture of an infant with true mosaic complete tetrasomy 21.
Asunto(s)
Trastornos de los Cromosomas/genética , Discapacidades del Desarrollo/genética , Síndrome de Down/genética , Tetrasomía/genética , Anomalías Múltiples , Aneuploidia , Trastornos de los Cromosomas/epidemiología , Trastornos de los Cromosomas/patología , Discapacidades del Desarrollo/patología , Síndrome de Down/patología , Femenino , Defectos de los Tabiques Cardíacos/genética , Defectos de los Tabiques Cardíacos/patología , Enfermedad de Hirschsprung/genética , Enfermedad de Hirschsprung/patología , Humanos , Lactante , Recién Nacido , Cariotipificación , Microcefalia/genética , Microcefalia/patología , Mosaicismo , Fenotipo , Tetrasomía/patologíaRESUMEN
Complete or partial tetrasomy 21 has been reported only in rare cases. We report a Japanese female patient with tetrasomy 21 due to an extra chromosome derived from chromosome 21 (Chr21). The patient had severe psychomotor retardation without Down syndrome (DS) phenotype; she showed short stature, microcephaly, round face, cleft lip and palate, and other dysmorphic features. The chromosome analyses for the patient detected an extra dicentric Chr21 consisting of two partial Chr21 copies fused together within their long arms. Her karyotype was revealed to be 47,XX,+dic(21;21). Allelic ratios of heterozygous SNPs observed in the patient indicated the maternal origin of the extra Chr21. Copy number and structural variant analyses using whole genome sequencing data indicated that the distal breakpoint of the dicentric Chr21 was located within 21q21.3 and that the extra Chr21 did not simply consist of inverted duplications of the pterâq21.3 region, but likely contained multiple partial deletions, duplications, and inversions within it. Fluorescence in situ hybridization results were consistent with the karyotype and genomic analyses. The patient's lack of DS phenotype turned out to be due to the normal copy number of the DS critical region (21q22.13-22.3). A possible molecular mechanism leading to the complex genomic rearrangements in the tetrasomic region consists mainly of breakage-fusion-bridge cycles with an unequal crossing-over event.
Asunto(s)
Anomalías Múltiples/genética , Cromosomas Humanos Par 21/genética , Discapacidad Intelectual/genética , Tetrasomía , Niño , Labio Leporino/genética , Fisura del Paladar/genética , Femenino , Humanos , Hibridación Fluorescente in Situ , Cariotipo , Cariotipificación , Microcefalia/genética , Fenotipo , Secuenciación Completa del GenomaRESUMEN
BACKGROUND: Tetrasomy 21 is a very rare aneuploidy which could clinically resemble a Down syndrome. It was most often described in its partial form than complete. We report the prenatal, pathological and genetic characteristics of a fetus with mosaic complete tetrasomy 21. This is the second well-documented description of a complete tetrasomy 21 in the literature. METHODS: Prenatal and fetal pathological examinations, cytogenetic and molecular analyses were performed to characterize fetal features with tetrasomy 21. RESULTS: Prenatal ultrasound examination revealed an isolated complete atrioventricular septal defect with normal karyotype on amniotic fluid. After termination of pregnancy, clinical examination of the fetus evoked trisomy 21 or Down syndrome. Chromosomal microarray analysis and FISH on lung tissue showed a mosaicism with four copies of chromosome 21 (tetrasomy 21). CONCLUSION: Our observation and the review of the literature reported the possibility of very weak mosaicism and disease-causing confined tissue-specific mosaicism in fetus or alive patients with chromosome 21 aneuploidy, mainly Down syndrome. In case of clinical diagnosis suggestive of Down syndrome, attention must be paid to the risk of false-negative test due to chromosomal mosaicism (very weak percentage, different tissue distribution). To overcome this risk, it is necessary to privilege the diagnostic techniques without culture step and to increase the number of cells and tissues analyzed, if possible. This study highlights the limits of microarray as the unique diagnostic approach in case of weak mosaic and French cytogenetics guidelines recommend to check anomalies seen in microarray by another technique on the same tissue.