Autor(es):
Simão, Laurentino 
; Alves, Cristina ; Brito, Filomena ; Marques, Bárbara ; Ferreira, Cristina ; Gaspar, Isabel ; Dieudonne, V. ; Cabral, P. ; Meneses, I. ; Duarte, Guida ; Correia, Hildeberto
Data: 2013
Identificador Persistente: http://hdl.handle.net/10400.18/2042
Origem: Repositório Científico do Instituto Nacional de Saúde
Assunto(s): Smith-Magenis Syndrome; Complex Chromosomal Rearrangement; Genotype/phenotype; Doenças Genéticas
Descrição
Smith-Magenis Syndrome (SMS) is a micro-deletion syndrome, and encompasses a picture of dysmorphology, mental defect, and fractious behavior.
Evaluation of complex chromosome rearrangements (CCRs) and their potential phenotypic consequences is a common challenge in the genetics clinic and knowledge about the genotype/phenotype relationships are limited.
We report the case of a 14-year-old boy who was referred by SMS, presenting developmental delay, fractious behavior, reduced sensitivity to pain, macrocranium and distinctive facial features. Following karyotyping, fluorescence in situ hybridization (FISH) using WCP probes for the chromosomes involved in CCR and 17p11.2 probe for SMS region was performed. Lately, chromosomal Comparative Genomic Hybridization (cCGH) and genomic microarray studies were also performed in order to identify genomic imbalances.
The cytogenetic analysis revealed a karyotype:
46,XY,inv(3)(p23q27)t(3;10)(p13.2;p11.2),inv(14)(q13q32)dn.ish inv(3)t(3;10)(wcp10+), der(10)t(3;10)(wcp3+),inv(14)(wcp14+). Parental karyotypes were normal, although the father presented a marked cognitive delay. FISH analyses showed no deletion in 17p11.2 region and confirmed the cytogenetic results, namely the presence of CCR. Additionally, cCGH and genomic microarray studies did not reveal any gains/losses of genetic material in the breakpoints regions.
Despite the clinical features of SMS, deletions or duplications in the SMS critical region were not detected in this patient. However, a small number of SMS present a mutation in the RAI1 gene instead of a 17p11.2 deletion, the former cause could not be excluded On the other hand, in CCRs de novo, an apparently balanced karyotype may be associated with an abnormal phenotype, including an increased risk of intellectual delay and congenital malformations. Further studies comprising, e.g., sequencing of the breakpoints, chromatin conformation analysis and refinement of the SMS critical region analysis might be useful to elucidate the phenotypic characteristics. However, the patient has been absent of routine clinical reevaluation; the etiology of the father’s cognitive delay could help shedding some light on the patient phenotypic features.
