De novo NSD1 mutation leading to Sotos syndrome – First case report from Oman

Multiple factors control the growth of a child, including genetics, nutrition, and socioeconomic factors. Referral of tallboys who are otherwise well is very rare. However, sometimes, extraordinary tall stature for the age can be a cause of great concern to the parents. We report a case of an Omani child with a de novo mutation of NSD1 that led to his overgrowth and diagnosis of Sotos syndrome (SoS). This syndrome is a rare genetic disorder. Only two cases of genetically proven diagnosis were reported from the Middle East and North Africa region. Therefore, we describe a case and highlight the comorbidities associated with this condition, encouraging colleagues from the region to report their cases to understand better the phenotype–genotype and the natural history of this disorder in this part of the world.

Keywords

NSD1 - Oman - overgrowth - tall stature

Financial support and sponsorship

Nil.

Publication History

Received: 14 July 2021

Accepted: 05 September 2021

Article published online:
14 July 2022

• References

• 1 Abdalla E, Bartsch O, Galetzka D, Zechner U. Novel clinical findings in the first Egyptian case of Sotos syndrome caused by complete deletion of the NSD1 gene. Am J Med Genet A 2017;173A: 1090-3.
• 2 Westerberg B. Soto Syndrome. Available from: https://www.socialstyrelsen.se/stod-i-arbetet/ovanliga-diagnoser/sotos-syndrom/. [Last accessed on 2020 Jan 24].
• 3 Baujat G, Cormier-Daire V. Sotos syndrome. Orphanet J Rare Dis 2007;2:36.
• 4 Albuquerque EV, Scalco RC, Jorge AA. Management of endocrine disease: Diagnostic and therapeutic approach of tall stature. Eur J Endocrinol 2017;176:R339-53.
• 5 Sotos JF, Dodge PR, Muirhead D, Crawford JD, Talbot NB. Cerebral gigantism in childhood. A syndrome of excessively rapid growth and acromegalic features and a nonprogressive neurologic disorder. N Engl J Med 1964;271:109-16.
• 6 Cole TR, Hughes HE. Sotos syndrome: A study of the diagnostic criteria and natural history. J Med Genet 1994;31:20-32.
• 7 Nagai T, Matsumoto N, Kurotaki N, Harada N, Niikawa N, Ogata T, et al. Sotos syndrome and haploinsufficiency of NSD1: Clinical features of intragenic mutations and submicroscopic deletions. J Med Genet 2003;40:285-9.
• 8 Rio M, Clech L, Amiel J, Faivre L, Lyonnet S, Le Merrer M, et al. Spectrum of NSD1 mutations in Sotos and weaver syndromes. J Med Genet 2003;40:436-40.
• 9 Tei S, Tsuneishi S, Matsuo M. The first Japanese familial Sotos syndrome with a novel mutation of the NSD1 gene. Kobe J Med Sci 2006;52:1-8.
• 10 Balasubramanian M, Shearing E, Smith K, Chavasse R, Taylor R, Tatton-Brown K, et al. Pneumothorax from subpleural blebs – A new association of Sotos syndrome? Am J Med Genet A 2014;164A: 1222-6.
• 11 Ha K, Anand P, Lee JA, Jones JR, Kim CA, Bertola DR, et al. Steric clash in the SET domain of histone methyltransferase NSD1 as a cause of Sotos syndrome and its genetic heterogeneity in a Brazilian cohort. Genes 2016;7:96.
• 12 Waggoner DJ, Raca G, Welch K, Dempsey M, Anderes E, Ostrovnaya I, et al. NSD1 analysis for Sotos syndrome: Insights and perspectives from the clinical laboratory. Genet Med 2005;7:524-33.
• 13 Carrasco Salas P, Palma Milla C, Lezana Rosales JM, Benito C, Franco Freire S, López Siles J. Hyperinsulinemic hypoglycemia in a patient with an intragenic NSD1 mutation. Am J Med Genet A 2016;170A: 544-6.
• 14 Carapito R, Isidor B, Guerouaz N, Untrau M, Radosavljevic M, Launay E, et al. Homozygous IL36RN mutation and NSD1 duplication in a patient with severe pustular psoriasis and symptoms unrelated to deficiency of interleukin-36 receptor antagonist. Br J Dermatol 2015;172:302-5.
• 15 Farhangdoost N, Horth C, Hu B, Bareke E, Chen X, Li Y, et al. Chromatin dysregulation associated with NSD1 mutation in head and neck squamous cell carcinoma. Cell Rep 2021;34:1-15.
• 16 Saletta F, Dalla Pozza L, Byrne JA. Genetic causes of cancer predisposition in children and adolescents. Transl Pediatr 2015;4:67-75.