Sotos syndrome

Was ist Sotos syndrome?

Sotos syndromeist eine genetische Störung, die durch übermäßiges Wachstum bei Personen mit dem syndrom.

Dieses übermäßige Wachstum beginnt normalerweise im Säuglingsalter (aber pränatale Fälle wurden dokumentiert) und dauert bis ins Jugendalter. Sie wird oft von einem fortgeschrittenen Knochenalter begleitet.

Das syndrom tritt in 1 bei 14,000 Lebendgeburten auf und betrifft Männer und Frauen gleichermaßen.

Syndrom Synonyme:
Zerebraler Gigantismus

Was Genveränderungen verursachen Sotos syndrome?

In 90% der Fälle tritt das Syndromes aufgrund von Mutationen im NSD1-Gen auf. Obwohl weitere Untersuchungen darauf hinweisen, dass Mutationen im NFIX- und APC2-Gen ebenfalls Ursachen haben können.

Im Fall einer autosomal dominanten Vererbung ist nur ein Elternteil der Träger der Genmutation, und sie haben eine 50% ige Chance, sie an jedes ihrer Kinder weiterzugeben. Syndromes, die in einer autosomal dominanten Vererbung vererbt werden, werden durch nur eine Kopie der Genmutation verursacht.

Was sind die wichtigsten symptome von Sotos syndrome?

Das Wichtigste symptome von Sotos syndrome kann von Person zu Person variieren und kann auch im Ausmaß ihres Schweregrades variieren.

Das syndromZu den typischen Gesichtsmerkmalen gehören ein großer Kopf, ein langes, schmales Gesicht und eine hohe Stirn. Gerötete Wangen und ein spitzes Kinn und weit auseinander stehende Augen, ein hoher Gaumen und ein fliehender Haaransatz sind gemeinsame Merkmale des syndrom.

Sonstiges Potenzial symptome umfassen angeborene Herzfehler, obwohl sie selten schwerwiegend sind, Krampfanfälle und Skoliose in 40 % der Fälle.

Intellektuelle Behinderung und Entwicklungsverzögerung sind auch bei Personen mit diagnostiziertem syndrom, insbesondere Sprachverzögerung.

Gleichgewichts- und Mobilitätsprobleme sind ebenfalls üblich symptome.

Mögliche klinische Merkmale/Merkmale:
Angst, beschleunigte Skelettreifung, Skoliose, geistige Behinderung, langes Gesicht, schmales Gesicht, autosomal-dominante Vererbung, Überwucherung

Wie wird jemand getestet? Sotos syndrome?

Die ersten Tests für Sotos syndrome kann mit einem Gesichtsanalyse-Screening beginnen, durch die FDNA Telehealth Telegenetik-Plattform, die die Schlüsselmarker der syndrom und skizzieren Sie die Notwendigkeit weiterer Tests. Es folgt ein Beratungsgespräch mit einem genetischen Berater und dann einem Genetiker. 

Basierend auf dieser klinischen Konsultation mit einem Genetiker werden die verschiedenen Optionen für Gentests geteilt und die Zustimmung für weitere Tests eingeholt.

Medizinische Informationen zu 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.
If you find a mistake or would like to contribute additional information, please email us at: [email protected]

Erhalten Sie eine schnellere und genauere Genetische Diagnostik!

Mehr als 250,000 Patienten erfolgreich analysiert!
Warten Sie nicht Jahre auf eine Diagnose. Handeln Sie jetzt und sparen Sie wertvolle Zeit.

Los geht's!

"Unser Weg zu einer Diagnose seltener Krankheiten war eine 5 -jährige Reise, die ich nur als Versuch beschreiben kann, einen Roadtrip ohne Karte zu unternehmen. Wir kannten unseren Ausgangspunkt nicht. Wir kannten unser Ziel nicht. Jetzt haben wir Hoffnung. "


Paula und Bobby
Eltern von Lillie

Was ist FDNA Telehealth?

FDNA Telehealth ist ein führendes Unternehmen für digitale Gesundheit, das einen schnelleren Zugang zu genauen genetischen Analysen bietet.

Mit einer von führenden Genetikern empfohlenen Krankenhaustechnologie verbindet unsere einzigartige Plattform Patienten mit Genexperten, um ihre dringendsten Fragen zu beantworten und eventuelle Bedenken hinsichtlich ihrer Symptome zu klären.

Vorteile von FDNA Telehealth



Unsere Plattform wird derzeit von über 70% der Genetiker verwendet und wurde zur Diagnose von über 250,000 Patienten weltweit eingesetzt.



FDNA Telehealth bietet innerhalb von Minuten eine Gesichtsanalyse und ein Screening, gefolgt von einem schnellen Zugang zu genetischen Beratern und Genetikern.



Unser nahtloser Prozess beginnt mit einer ersten Online-Diagnose durch einen genetischen Berater, gefolgt von Konsultationen mit Genetikern und Gentests.


Genauigkeit & Präzision

Erweiterte Funktionen und Technologien für künstliche Intelligenz (KI) mit einer Genauigkeitsrate von 90% für eine genauere genetische analyse.



Schnellerer Zugang zu genetischen Beratern, Genetikern, Gentests und einer Diagnose. Falls erforderlich, innerhalb von 24 Stunden. Sparen Sie Zeit und Geld.


Privatsphäre & Sicherheit

Wir garantieren den größtmöglichen Schutz aller Bilder und Patienteninformationen. Ihre Daten sind immer sicher und verschlüsselt.

FDNA Telehealth kann Sie einer Diagnose näher bringen.
Vereinbaren Sie innerhalb von 72 Stunden ein Online-Treffen zur genetischen Beratung!