Malan syndrome in a patient with 19p13.2p13.12 deletion encompassing NFIX and CACNA1A genes: Case report and review of the literature

被引:10
作者
Bellucco, Fernanda T. [1 ]
de Mello, Claudia B. [2 ]
Meloni, Vera A. [1 ]
Melaragno, Maria Isabel [1 ]
机构
[1] Univ Fed Sao Paulo, Dept Morphol & Genet, Sao Paulo, Brazil
[2] Univ Fed Sao Paulo, Dept Psychobiol, Sao Paulo, Brazil
关键词
19p13.2; microdeletion; CACNA1A; Malan syndrome; NFIX; overgrowth disorder; FAMILIAL HEMIPLEGIC MIGRAINE; DNA-BINDING/DIMERIZATION DOMAIN; SOTOS-LIKE OVERGROWTH; MUTATIONS; EPILEPSY; MICRODELETION; VARIANTS; GENOTYPE; SPECTRUM; ATAXIA;
D O I
10.1002/mgg3.997
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Background: Malan syndrome is a recently introduced overgrowth disorder described in a limited number of individuals. Haploinsufficiency and also point mutations of NFIX gene have been proposed as its leading causative mechanism, however, due to the limited number of cases and different deletion sizes, genotype/phenotype correlations are still limited. Methods: Here, we report the first Brazilian case of Malan syndrome caused by a 990 kb deletion in 19p13.2p13.12, focusing on clinical and behavioral aspects of the syndrome. Results: The patient presented with macrocephaly, facial dysmorphisms, hypotonia, developmental delay, moderate thoracolumbar scoliosis, and seizures. The intellectual and behavioral assessments showed severe cognitive, language, and adaptive functions impairments. The 19p deleted region of our patient encompasses NFIX, CACNA1A, which seems to be related to a higher frequency of seizures among individuals with microdeletions in 19p13.2, and 15 other coding genes, including CC2D1A and NACC1, both known to be involved in neurobiological process and pathways. Conclusion: Deletions involving NFIX gene should be considered in patients with overgrowth during childhood, macrocephaly, developmental delay, and seizures, as well as severe intellectual disability.
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页数:6
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