Craniofacial and oral features of Sotos syndrome: Differences in patients with submicroscopic deletion and mutation of NSD1 gene

Abstract

Sotos syndrome is a well-known overgrowth syndrome caused by haploinsufficiency of NSD1 gene located at 5q35. There are two types of mutations that cause NSD1 haploinsufficiency: mutations within the NSD1 gene (mutation type) and a 5q35 submicroscopic deletion encompassing the entire NSD1 gene (deletion type). We investigated detailed craniofacial, dental, and oral findings in five patients with deletion type, and three patients with mutation type Sotos syndrome. All eight patients had a high palate, excessive tooth wear, crowding, and all but one patient had hypodontia and deep bite. Hypodontia was exclusively observed in the second premolars, and there were no differences between the deletion and mutation types in the number of missing teeth. Another feature frequently seen in common with both types was maxillary recession. Findings seen more frequently and more pronounced in deletion-type than in mutation-type included mandibular recession, scissors or posterior cross bite, and small dental arch with labioclination of the maxillary central incisors. It is noteworthy that although either scissors bite or cross bite was present in all of the deletion-type patients, neither of these was observed in mutation-type patients. Other features seen in a few patients include enamel hypoplasia (two deletion patients), and ectopic tooth eruption (one deletion and one mutation patients). Our study suggests that Sotos syndrome patients should be observed closely for possible dental and oral complications especially for malocculusion in the deletion-type patients.

Craniofacial and dental malformations in Costello syndrome: A detailed evaluation using multi‐detector row computed tomography

“…cast studies are often difficult to perform, especially in the infantile period when patients tend to show marked irritability. MDCT is a useful tool for precise evaluation of craniofacial and oral manifestations in multiple congenital anomaly/intellectual disability syndromes (Hirai et al 2011).…”

“…In addition, images reconstructed by MDCT were used as substitutes for dental cast study and panoramic and lateral cephalometric radiograph studies to evaluate the dental arches, tooth size, relationships between craniofacial and dental structures, and hypodontia. The following MDCT imaging conditions were used: window width, 1500; and window level, 450 (Hirai et al , 2011Yamauchi et al 2010). Crown and dental arch sizes were measured using Image J with a resolution accuracy of 0.1 mm.…”

Sotos Syndrome: A Case Report

“…4 Sendromun oral bulguları arasında hipodonti, mine hipoplazileri, tolon tüberkülleri, füzyon, geniş pulpa odaları, maksilla ve mandibulada diş eti çekilmesi, yüksek damak, dişlerde erozyon gözlenmektedir. 5 Literatürde otozomal dominant kalıtımın etkili olduğunu düşündüren, birbirini takip eden altı jenerasyonda benzer bulgular saptanan bir aile bildirilmiş olmasına karşın vakaların çoğu sporadiktir. 6 Sotos sendromu ile ilişkili olduğu bilinen tek gen olan NSD1, 2002 yılında klonlanmış olup olguların çoğunda mutasyonlar gosterilmiştir.…”

“…10 14 Sotos sendromunda NSD1 geninin mutasyonuna bağlı olarak maksiller dişlerin labiale açılanmalarında artış, mandibula gelişiminde gerilik, posterior cross-bite görülmektedir. 15 Literatüre bakıldığında distraksiyon osteogenezi ile tedavi edilen maxiller ve mandibular hipoplaziye bağlı bir retrüzyon vakası 16 ve süt dişlerinde yaygın hipoplazi bulgulanan bir vaka 17 ile premolar hipodontisinin gözlendiği bir vaka serisi bildirilmiştir. 18 Bu hastalar maloklüzyon, dental sağlık ve eşlik edebilecek oral komplikasyonlar açısından takip edilmelidirler.…”

A Clinical Review of Generalized Overgrowth Syndromes in the Era of Massively Parallel Sequencing

“…Patients often have advanced bone age, congenital heart disease (20%), ventriculomegaly or other central nervous system abnormalities identified at MRI, renal abnormalities (15%), scoliosis (30%), seizures (25%), and tumors (3%). Heterozygous mutations of NSD1 are responsible, and it is estimated that a mutation will be detected in over 90% of the patients (5-10% are larger deletions detected by MLPA or cytogenetic studies) following accurate phenotyping Rahman, 2004, 2007;Cecconi et al, 2005;Douglas et al, 2005;Tatton-Brown et al, 2005;Fickie et al, 2011;Hirai et al, 2011].…”