Abstract This article reports on the clinical and genetic characteristics of monozygotic twins with Marshall-Smith syndrome (MRSHSS) due to a mutation in the NFIX gene, along with a review of related literature. Both patients presented with global developmental delays, a prominent forehead, shallow eye sockets, and pectus excavatum. Genetic testing revealed a heterozygous splicing site mutation c.697+1G>A in both children, with parents showing wild-type at this locus. According to the guidelines of the American College of Medical Genetics and Genomics, this mutation is considered likely pathogenic and has not been previously reported in the literature. A review of the literature identified 32 MRSHSS patients with splicing/frameshift mutations. Accelerated bone maturation and moderate to severe global developmental delay/intellectual disability are the primary clinical manifestations of patients with MRSHSS. Genetic testing results are crucial for the diagnosis of this condition.
LIN Xue-Qin,QUAN Yu-Lin,HE Hai-Lan et al. NFIX gene mutation causes Marshall-Smith syndrome in a pair of identical twins and literature review[J]. CJCP, 2024, 26(7): 750-756.
LIN Xue-Qin,QUAN Yu-Lin,HE Hai-Lan et al. NFIX gene mutation causes Marshall-Smith syndrome in a pair of identical twins and literature review[J]. CJCP, 2024, 26(7): 750-756.
Marshall RE, Graham CB, Scott CR, et al. Syndrome of accelerated skeletal maturation and relative failure to thrive: a newly recognized clinical growth disorder[J]. J Pediatr, 1971, 78(1): 95-101. PMID: 4321601. DOI: 10.1016/s0022-3476(71)80269-x.
Malan V, Rajan D, Thomas S, et al. Distinct effects of allelic NFIX mutations on nonsense-mediated mRNA decay engender either a Sotos-like or a Marshall-Smith syndrome[J]. Am J Hum Genet, 2010, 87(2): 189-198. PMID: 20673863. PMCID: PMC2917711. DOI: 10.1016/j.ajhg.2010.07.001.
Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology[J]. Genet Med, 2015, 17(5): 405-424. PMID: 25741868. PMCID: PMC4544753. DOI: 10.1038/gim.2015.30.
Schanze D, Neubauer D, Cormier-Daire V, et al. Deletions in the 3' part of the NFIX gene including a recurrent alu-mediated deletion of exon 6 and 7 account for previously unexplained cases of Marshall-Smith syndrome[J]. Hum Mutat, 2014, 35(9): 1092-1100. PMID: 24924640. DOI: 10.1002/humu.22603.
Martinez F, Marín-Reina P, Sanchis-Calvo A, et al. Novel mutations of NFIX gene causing Marshall-Smith syndrome or Sotos-like syndrome: one gene, two phenotypes[J]. Pediatr Res, 2015, 78(5): 533-539. PMID: 26200704. DOI: 10.1038/pr.2015.135.
Aggarwal A, Nguyen J, Rivera-Davila M, et al. Marshall-Smith syndrome: novel pathogenic variant and previously unreported associations with precocious puberty and aortic root dilatation[J]. Eur J Med Genet, 2017, 60(7): 391-394. PMID: 28442439. DOI: 10.1016/j.ejmg.2017.04.012.
Bupp C, Junewick J, Hess JL. A de-novo NFIX mutation causes a case of neonatal lethal Marshall-Smith syndrome[J]. Clin Dysmorphol, 2020, 29(4): 214-216. PMID: 32701632. DOI: 10.1097/MCD.0000000000000339.
Zenker M, Bunt J, Schanze I, et al. Variants in nuclear factor I genes influence growth and development[J]. Am J Med Genet C Semin Med Genet, 2019, 181(4): 611-626. PMID: 31730271. DOI: 10.1002/ajmg.c.31747.
Mulder PA, van Balkom IDC, Landlust AM, et al. Development, behaviour and sensory processing in Marshall-Smith syndrome and Malan syndrome: phenotype comparison in two related syndromes[J]. J Intellect Disabil Res, 2020, 64(12): 956-969. PMID: 33034087. PMCID: PMC8957705. DOI: 10.1111/jir.12787.
Klaassens M, Morrogh D, Rosser EM, et al. Malan syndrome: Sotos-like overgrowth with de novo NFIX sequence variants and deletions in six new patients and a review of the literature[J]. Eur J Hum Genet, 2015, 23(5): 610-615. PMID: 25118028. PMCID: PMC4402637. DOI: 10.1038/ejhg.2014.162.
