Rett-like Syndrome in a Pediatric Patient—A Challenging Diagnosis

Abstract

Neurodevelopmental disorders with features overlapping Rett's syndrome frequently remain unexplained in patients without disease-causing variants in MECP2. Variants in IQSEC2 frequently cause nonsyndromic X-linked intellectual disability (XLID), although de novo variants may cause a severe syndrome that resembles Rett and Angelman's syndrome. We report a 7-year-old girl presenting severe neurodevelopmental delay, stereotypic hand movements, hypotonia, autistic-like features, inappropriate laughing/screaming spells, and symmetrical hypomyelination. A whole exome sequencing detected a novel de novo heterozygous truncating variant within the IQSEC2 gene. Variants of IQSEC2 should be considered in patients with Rett–Angelman phenotype spectrum and autistic features when those causes were excluded.

Keywords

whole exome sequencing - IQSEC2 - mental retardation - X-linked

Publikationsverlauf

Eingereicht: 28. Januar 2020

Angenommen: 03. Juni 2020

Artikel online veröffentlicht:
10. August 2020

• References

• 1 Renieri A, Meloni I, Longo I. et al. Rett syndrome: the complex nature of a monogenic disease. J Mol Med (Berl) 2003; 81 (06) 346-354
• 2 Gold WA, Krishnarajy R, Ellaway C, Christodoulou J. Rett syndrome : a genetic update and clinical review focusing on comorbidities. ACS Chem Neurosci 2018; 9 (02) 167-176
• 3 Srivastava S, Desai S, Cohen J. et al. Monogenic disorders that mimic the phenotype of Rett syndrome. Neurogenetics 2018; 19 (01) 41-47
• 4 Olson HE, Tambunan D, LaCoursiere C. et al. Mutations in epilepsy and intellectual disability genes in patients with features of Rett syndrome. Am J Med Genet A 2015; 167A [phone]
• 5 Alexander-Bloch AF, McDougle CJ, Ullman Z, Sweetser DA. IQSEC2 and X-linked syndromal intellectual disability. Psychiatr Genet 2016; 26 (03) 101-108
• 6 Shoubridge C, Tarpey PS, Abidi F. et al. Mutations in the guanine nucleotide exchange factor gene IQSEC2 cause nonsyndromic intellectual disability. Nat Genet 2010; 42 (06) 486-488
• 7 Kalscheuer VM, James VM, Himelright ML. et al. Novel missense mutation A789V in IQSEC2 underlies X-linked intellectual disability in the MRX78 family. Front Mol Neurosci 2016; 8: 85
• 8 Shoubridge C, Harvey RJ, Dudding-Byth T. IQSEC2 mutation update and review of the female-specific phenotype spectrum including intellectual disability and epilepsy. Hum Mutat 2019; 40 (01) 5-24
• 9 Tran Mau-Them F, Willems M, Albrecht B. et al. Expanding the phenotype of IQSEC2 mutations: truncating mutations in severe intellectual disability. Eur J Hum Genet 2014; 22 (02) 289-292
• 10 Mignot C, McMahon AC, Bar C. et al. IQSEC2-related encephalopathy in males and females: a comparative study including 37 novel patients. Genet Med 2019; 21 (04) 837-849
• 11 Helm BM, Powis Z, Prada CE. et al. The role of IQSEC2 in syndromic intellectual disability: narrowing the diagnostic odyssey. Am J Med Genet A 2017; 173 (10) 2814-2820
• 12 Tzschach A, Grasshoff U, Beck-Woedl S. et al. Next-generation sequencing in X-linked intellectual disability. Eur J Hum Genet 2015; 23 (11) 1513-1518