title: Malan syndrome (Sotos syndrome 2) in two patients with 19p13.2 deletion encompassing NFIX gene and novel NFIX sequence variant.
abstract: OBJECTIVE
  Sotos syndrome 2 (MIM #614753), known also as Malan syndrome, is caused by heterozygous mutations/deletions of the NFIX gene located on chromosome 19p13.2. It manifests in developmental delay, intellectual impairment, macrocephaly, central nervous system anomalies, postnatal overgrowth, and craniofacial dysmorphism. Unusual behavior with/without autistic traits, ophthalmologic, gastrointestinal, musculo-skeletal, and hand/foot abnormalities are also frequent. Due to the limited number of such cases, no definitive conclusions about genotype-phenotype correlations have been possible. In the following paper, we discuss physical features consistent with Sotos syndrome 2 based on literature review and two new cases [a patient with de novo 19p13.2 deletion encompassing a part of the NFIX gene and a patient with de novo (not described so far) heterozygous missense mutation c.367C>T (p.Arg123Trp) in the NFIX gene].
  
  
  RESULTS
  Apart from overgrowth and psychomotor developmental delay, the most consistent physical features of our two patients are dysmorphism including high forehead, downslanting palpebral fissures, pointed chin, and abnormalities of the pinna. Both show abnormal behavior and present with long, tapered fingers and toenail defect. No severe congenital malformations were noted.
  
  
  CONCLUSIONS
  We hope these data will serve as a material for further studies and provide an opportunity to make more reliable genotype-phenotype correlations.
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Jezela-Stanek
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Marzena
authors.initials: M
authors.lastname: Kucharczyk
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Falana
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Jurkiewicz
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Marlena
authors.initials: M
authors.lastname: Mlynek
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Wicher
authors.affiliation: Department of Medical Genetics, Warsaw Medical University, Warsaw, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Rydzanicz
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.|Department of Child and Adolescent Psychiatry, Warsaw Medical University, Warsaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Kugaudo
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Cieslikowska
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Ciara
authors.affiliation: Department of Medical Genetics, Warsaw Medical University, Warsaw, Poland.
authors.forename: Rafal
authors.initials: R
authors.lastname: Ploski
authors.affiliation: Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Krajewska-Walasek
mesh_terms: D002648:Child; D002872:Chromosome Deletion; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D019465:Craniofacial Abnormalities / Q000235:genetics; D002658:Developmental Disabilities / Q000235:genetics; D005260:Female; D006579:Heterozygote; D006801:Humans; D020125:Mutation, Missense / Q000235:genetics; D051839:NFI Transcription Factors / Q000235:genetics*; D010641:Phenotype; D058495:Sotos Syndrome / Q000235:genetics*
chemical_list: D051839:NFI Transcription Factors; C000594474:NFIX protein, human
keywords: 19p13.2 deletion; Malan syndrome; NFIX gene; NFIX mutation; Sotos syndrome 2