Biomedical papers, 2016 (vol. 160), issue 1

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2016, 160(1):161-167 | 10.5507/bp.2016.006

Malan syndrome (Sotos syndrome 2) in two patients with 19p13.2 deletion encompassing NFIX gene and novel NFIX sequence variant

Aleksandra Jezela-Staneka, Marzena Kucharczyka, Katarzyna Falanaa, Dorota Jurkiewicza, Marlena Mlyneka, Dorota Wichera, Malgorzata Rydzaniczb, Monika Kugaudoa,c, Agata Cieslikowskaa, Elzbieta Ciaraa, Rafal Ploskib, Malgorzata Krajewska-Walaseka
a Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland
b Department of Medical Genetics, Warsaw Medical University, Warsaw, Poland
c Department of Child and Adolescent Psychiatry, Warsaw Medical University, Warsaw, Poland

Background and Aim. 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.

Keywords: Malan syndrome, Sotos syndrome 2, NFIX gene, 19p13.2 deletion, NFIX mutation

Received: September 14, 2015; Accepted: February 3, 2016; Prepublished online: February 29, 2016; Published: March 30, 2016


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