Paula et Bobby
Parents de Lillie
Qu'est-ce que Sotos syndrome?
Sotos syndrome is a genetic disorder characterized by excessive growth in individuals with the syndrome.
This excessive growth usually begins in infancy (but prenatal cases have been documented) and lasts through adolescence. It is often accompanied by advanced bone age.
The syndrome occurs in 1 in 14,000 live births and affects males and females similarly.
Quelles sont les causes des changements génétiques Sotos syndrome?
Dans 90% des cas, le syndrome est dû à des mutations du gène NSD1. Bien que d'autres recherches suggèrent que des mutations dans le gène NFIX et APC2 peuvent également être des causes contributives.
Dans le cas de l'hérédité autosomique dominante, un seul parent est porteur de la mutation génique, et ils ont 50% de chances de la transmettre à chacun de leurs enfants. Les les syndromes hérités d'une transmission autosomique dominante sont causés par une seule copie de la mutation génique.
Quels sont les principaux symptômes de Sotos syndrome?
The main symptoms of Sotos syndrome may vary between individuals and may also vary in the extent of their severity.
The syndrome's typical facial characteristics include a large head, long, narrow face, and a high forehead. Flushed cheeks and a pointed chin and widely spaced eyes, a high palate, and receding hairline are common features of the syndrome.
Other potential symptoms include congenital heart defects, although they are rarely severe, seizures, and scoliosis in 40% of cases.
Intellectual disability and developmental delay are also common among individuals diagnosed with the syndrome, particularly speech delay.
Balance and mobility issues are also common symptoms.
Possible clinical traits/features:
Anxiety, Accelerated skeletal maturation, Scoliosis, Intellectual disability, Long face, Narrow face, Autosomal dominant inheritance, Overgrowth
Comment quelqu'un se fait-il tester pour Sotos syndrome?
Les premiers tests de Sotos syndrome peut commencer par un dépistage par analyse faciale, en passant par le FDNA Telehealth plateforme de télégénétique, qui permet d'identifier les marqueurs clés de la syndrome et souligner la nécessité de tests supplémentaires. Une consultation avec un conseiller génétique puis un généticien suivra.
Sur la base de cette consultation clinique avec un généticien, les différentes options pour les tests génétiques seront partagées et le consentement sera recherché pour des tests supplémentaires.
Informations médicales sur Sotos syndrome
Sotos syndrome 1 combines early overgrowth with a characteristic facial appearance (macrocephaly, broad and prominent forehead, downslanting palpebral fissures, long chin) and sometimes intellectual disability. Advanced bone age, cardiac anomalies, cranial MRI/CT abnormalities, and joint hyperlaxity are common. The syndrome is caused by heterozygous mutations in the NSD1 gene or by deletions in the 5q35 region (Kurotaki et al., (2002), Imaizumi et al., (2002)).
Familial cases have been reported (Bale et al., 1985; Scarpa et al., 1994; Smith et al., 1980; Winship et al., 1985; Opitz et al., 1998).
Cole et al., (1992) reported a 22-year-old woman who developed a small cell carcinoma of the lung.
Hersh et al., (1992) concluded that the childhood malignancy risk is ""probably lower than 2.2%"" from a questionnaire survey of geneticists.
Corsello et al., (1996) reported one case with non-Hodgkin lymphoma and one with an acute lymphoblastic leukemia, although from the clinical photographs the diagnosis was not absolutely typical of Sotos - see also the comments by Cole and Allanson (1998), Corsello and Giuffre (1998), and Cohen (1999). Leonard et al., (2000) reported two cases with sacrococcygeal teratomas. The patient reported by Deardorff et al., (2004) had a ganglioglioma.
Reported malignancies include Wilms tumor, hepatocarcinoma, neuroblastoma, and leukemias (Martinez-Glez and Lapunzina, 2007).
Cole and Hughes (1994) provide a good review of the clinical features. Features can be very variable - see family reported by Donnelly et al., (2011).
The face is characterized by macrocephaly, a high prominent forehead, downslanting palpebral fissures, a long pointed chin, and a high-arched palate. The birth weight may be increased with an enlarged head circumference. In childhood, height is excessive, with an advanced bone age and large hands and feet, although the final adult height may not be increased (Agwu et al., 1999).
The cerebral ventricles may appear mildly dilated on CT scan (Schaefer et al., 1997). The authors also noted that hypoplasia of the corpus callosum and cavum septum pellucidum are common.
Noreau et al., (1998) and Tsukahara et al., (1999) reported cases with congenital heart disease (note that left ventricular noncompaction might occur - Martinez et al., (2011). These were present in 30-40% of Japanese patients but apparently a lower percentage in other ethnic groups.
Robertson and Bankier (1999) reported three children with features of Sotos syndrome but with a normal bone age, together with cutis laxa, joint hypermobility and vesicoureteric reflux. The facies seemed typical for Sotos syndrome, but again this may be a separate subgroup. Mutations in NSD1 have now been found in this family (Hood et al., 2016), so that profound joint laxity and aortic dilatation is part of Sotos syndrome.
Melo et al., (2000) review the neuroimaging and echocardiographic findings in Sotos syndrome.
Amiel et al., (2002) report five unrelated cases with facial features of Sotos but with more severe developmental delay than expected.
Sweeney et al., (2002) reported two patients with severe scoliosis.
Tatton-Brown et al., (2005) reported the results of a multicenter genotype-phenotype study of 266 patients. Although there was an ascertainment bias in this study, Sotos syndrome was clinically diagnosed in 99% of patients with a mutation. Of the clinically diagnosed patients, a mutation (83%) or 5q35 microdeletion (10%) was found in 93%. Clinically, 10% of cases did not have an enlarged skull circumference or height. Patients with a microdeletion had less prominent overgrowth and more learning difficulties. Otherwise, there was no correlation between deletion size and clinical phenotype. The number of familial cases was small, possibly indicating reduced reproductive fitness in Sotos syndrome.
Nagai et al., (2003) looked at the clinical features of five patients with intragenic NSD1 mutations predicted to form a truncated NSD1 protein and in 21 patients with a fairly common ~2.2 Mb deletion involving the entire NSD1 gene. Overgrowth and advanced maturation in infancy to early childhood, intellectual disability, hypotonia, hyperreflexia, and characteristic minor anomalies were present in patients with mutations and deletions, whereas major anomalies in the central nervous system (agenesis or hypoplasia of the corpus callosum), cardiovascular system (patent ductus arteriosus and atrial septal defect), and urinary system (vesicoureteric reflux, hydronephrosis, and small kidney) were exclusively exhibited by patients with deletions.
Rio et al., (2003) studied 39 patients with childhood overgrowth. The series included typical Sotos patients (23), Sotos-like patients (10), and Weaver patients (6). They identified six NSD1 deletions and 16 intragenic mutations in Sotos or Sotos-like patients, and intragenic mutations in 3/6 Weaver patients. However, Tatton-Brown et al., (2005) mentioned that two of the Weaver cases were in fact typical Sotos cases, and the third was thought to have possible Sotos syndrome. Intellectual disability was consistently more severe in patients with NSD1 deletions.
Douglas et al., (2003) studied 75 patients with childhood overgrowth. Of the 37 patients with typical Sotos syndrome, 28 (76%) had a NSD1 mutation. In 13 patients with a Sotos-like syndrome but with atypical features, four mutations were found. Fifty-nine patients with congenital overgrowth (24 with classical facial features of Sotos, nine who were Sotos-like, two with Weaver and 24 with non-specific overgrowth) were looked at by Cecconi et al., (2005). Seventeen mutations were found, and these were all in the Sotos group. Heart defects (especially an ASD) were prominent. The occasional patient had neither macrocephaly nor advanced bone-age.
Turkmen et al., (2003) studied 20 cases of Sotos syndrome and found mutations in 18 (six nonsense, eight frameshifts, three splice site, one missense, one in-frame deletion). Further mutations were reported by Kamimura et al., (2003).
Hoglund et al., (2003) reported a father and son with a 1 bp deletion in the NSD1 gene.
The condition in those with a NSD1 mutation is well-reviewed by Tatton-Brown and Rahman (2004).
There are also families with non-syndromic overgrowth and NSD1 mutations (van Haelst et al., 2005). Note the child reported by Kanemoto et al., (2006) who had features of Nevo but had a Sotos (NSD1) mutation.
A duplication of the insulin-like growth factor on 15q26 might cause a Sotos-like phenotype and should be considered in those without a NSD1 mutation (Kant et al., 2007).
A mother and her two children all had normal intelligence and NSD1 mutations (Zechner et al., 2009). Two had bronchial asthma, and one had diabetes and massive accumulation of fat and fluid under the skin of the limbs and ankles.
Hypodontia of the mandibular premolars, enamel problems, and excessive wearing of the teeth are common features (Kotilainen et al., 2009).
A three-generation family (eight affected) was reported by Donnelly et al., (2011).
A duplication was reported by Kasnauskiene et al., (2011).
Two cases with subpleural blebs resulting in pneumothorax were reported by Balasubramanian et al., (2014).
Some patients with an overgrowth syndrome resembling Sotos may have NFIX mutations - see under Marshall-Smith syndrome.
A Brazilian cohort (Vieira et al., 2015) showed considerable molecular heterogeneity with only 19% found to have NSD1 mutations. One had a PTEN mutation.
There is an infrequent association with hypo- or hyper-thyroidism and with hyperinsulin hypoglycemia (Matsuo et al., 2013, Nakamura et al., 2015). Hyperinsulinemic hypoglycemia in the neonatal period might be a clue to the diagnosis (Salas et al., 2016).
A patient reported by McClelland et al., (2016) had a low birth weight and generalized lymphedema.
Sio et al., (2017) described a 2-year-old patient with Sotos syndrome and Hirschsprung disease.
Laccetta et al., (2017) described a family with heterozygous missense mutations in the NSD1. The proband exhibited full Sotos syndrome, whereas his mother and grandfather only had tall stature.
Abdalla et al., (2017) described an Egyptian boy with Sotos syndrome, who presented with lack of social interaction, attention deficit, absent speech and marked hypotonia. Audiogram showed severe bilateral sensorineural hearing loss. Brain MRI showed an arachnoid cyst. The authors identified heterozygous 1.9 Mb deletion (hg19, 5:175,460,087-177,400,270) in 5q35 region with three deleted genes (SLC34A1, NSD1, and F12). In addition, they identified a 0.3 Mb duplicated region in 5q35.3 (177,482,505-177,810,677) including two genes (NHP2 and AGXT2L2)."
* This information is courtesy of the L M D.
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Paula et Bobby
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