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Sotos Syndrome

Cerebral Gigantism

Sotos syndrome is an overgrowth condition that is defined by excessive growth, distinct facial features, and difficulties in learning. Other manifestations such as cardiac and genitourinary anomalies may also be present. This disorder is diagnosed by a physical exam, genetic testing, and possibly imaging.


Sotos syndrome describes a childhood overgrowth disorder that is remarkable for excessive growth, distinguished facial features, and learning disabilities [1] [2]. Additionally, neonates may present with feeding difficulties, hypotonia, hypoglycemia, and jaundice [3]. Most cases result from NSD1 mutations, of which the majority are sporadic while some are noted to be of autosomal dominant inheritance [1] [4]. Beckwith-Wiedeman syndrome and Fragile X syndrome are among the differential diagnoses [1].

Neonates with this overgrowth condition are above average in terms of their weight, length, and occipitofrontal circumference (OFC) [3]. There is a significant growth in the child's first 12 months, which eventually becomes stable [1]. At pubertal age, the growth is appropriate and eventually results in an adult height that falls in the upper range of the normal curve [5]. The OFC remains between 98th and 99.6th percentile throughout the affected individual's life [6]. Moreover, advanced bone age is observed in most patients [1].

Craniofacial dysmorphia in infancy is striking for a prominent forehead. In childhood, the facies are characterized by an elongated head, macrodolichocephaly, frontal bossing, hypertelorism, downward slanting palpebral fissures, pointed jaw, and a highly arched palate [1] [6]. These features are less apparent in adulthood although they still have a prominent jaw.

Individuals with Sotos syndrome also exhibit a developmental delay in motor and speech skills and experience a lag in milestones [1]. Additionally, they may demonstrate behavioral problems such as attention deficit hyperactivity disorder (ADHD) and others [7].

Other manifestations that may be observed in these patients include anomalies of the heart (septal defects) and genitourinary system [1] [2] [8]. Furthermore, affected children may also manifest with brisk deep tendon reflexes, scoliosis, and seizures [1] [2] [6].

  • ネルソン Nelson syndrome ネルソン症候群 Nicolas-Favre ニコラ・ファーブル Nicolas-Favre disease ニコラ・ファーブル病 Niemann-Pick ニーマン・ピック Niemann-Pick disease ニーマン・ピック病 AlbertNiemann (1880-1921) German pediatrician and Ludwig Pick (1868-1944) Germanpathologist died in concentrate camp[jams.med.or.jp]
Periorbital Fullness
  • Patients with microduplications including NSD1 appear to have a consistent phenotype consisting of short stature, microcephaly, learning disability or mild to moderate ID, and distinctive facial features comprising periorbital fullness, short palpebral[ncbi.nlm.nih.gov]
Hearing Impairment
  • Other signs of this syndrome are scoliosis , seizures, cardiac or renal defects, visual or hearing impairments. Jaundice has also been said to be associated in some cases with this disease.[epainassist.com]
  • Other signs of this syndrome are scoliosis, seizures, cardiac or renal defects, visual or hearing impairments. Jaundice has also been said to be associated in some cases with this disease.[epainassist.com]
Advanced Bone Age
  • Facial gestalt and macrocephaly, rather than advanced bone age, are the strongest indications for clinical diagnosis.[ncbi.nlm.nih.gov]
  • Abstract Sotos syndrome (cerebral gigantism) is characterized by macrocephaly, global developmental delay, characteristic facial dysmorphology, and a markedly advanced bone age.[ncbi.nlm.nih.gov]
  • Sotos syndrome, or cerebral gigantism, is a rare genetic condition characterized by tall stature, gigantism, dolichocephaly, advanced bone age and learning disability.[ncbi.nlm.nih.gov]
  • Moreover, advanced bone age is observed in most patients. Craniofacial dysmorphia in infancy is striking for a prominent forehead.[symptoma.com]
  • Sotos syndrome is a well-defined childhood overgrowth syndrome characterized by pre- and postnatal overgrowth, developmental delay, advanced bone age, and a typical facial gestalt including macrodolichocephaly with frontal bossing, frontoparietal sparseness[ncbi.nlm.nih.gov]
Large Hand
  • Haploinsufficiency of the NSD1 gene due to 5q35 microdeletions or intragenic mutations is the major cause of Sotos syndrome characterized by generalized overgrowth, large hands and feet with advanced bone age, craniofacial dysmorphic features, learning[ncbi.nlm.nih.gov]
  • The clinical features of the three patients included a typical facial gestalt with frontal bossing, prominent jaw and high anterior hairline; macrocephaly, dolichocephaly, large hands; neonatal hypotonia and jaundice.[ncbi.nlm.nih.gov]
  • Sotos syndrome is an overgrowth syndrome leading to peculiar facial characteristics, large hands and feet, and mental retardation. The maxillofacial characteristics are metopic protrusion, a high and narrow palate and a tapered mandible.[ncbi.nlm.nih.gov]
  • They may have a protruding forehead, large hands and feet, and downward-slanting eyes. Growth generally slows to normal around preschool, but intellectual disabilities may remain.[kidspot.com.au]
Large Feet
  • feet Hypertelorism Hypotonia Gum abscesses Unusually large body Delay in developmental milestones Epilepsy Advance teeth development Missing Teeth Weak Enamel Poor alignment of teeth Teeth discoloration Flat fingers Flat toenails Constipation Persistent[syndromespedia.com]
  • Figure 11 Large feet (A) and hands (B) with deep creases in case 3. He smiled at 4 weeks, sat alone at 12 months, crawled at 14 months, and walked at 2 years.[jmg.bmj.com]
Poor Coordination
  • coordination, risk for CA–eg, Wilms' tumor, liver, parotid, ovarian CAs So·tos syn·drome ( sō'tōs sin'drōm ) Cerebral gigantism and generalized large muscles in childhood, with mental retardation and defective coordination; of unknown etiology.[medical-dictionary.thefreedictionary.com]
  • Performance Abnormalities  MOTOR: Poor Coordination (Non progressive, gross fine) Hyper-reflexia Hypo-tonia (poor sucking may need NGF) Delayed Motor function  Variable Mental Deficiency: (IQ 40-129) Mean IQ 78  Expressive language delay  Significant[slideshare.net]
  • coordination and delayed motor skills primarily gross motor (swimming is sport many succeed in) Febrile convulsions in almost 50% Almost half with febrile seizure will go on to have nonfebrile seizures Seizures managed same as in other children/adults[en.wikibooks.org]
  • Most patients have a non progressive neurological dysfunction manifested by clumsiness and poor coordination.[ncbi.nlm.nih.gov]


Neonates and children presenting with the abovementioned features should undergo a workup that includes a physical exam and the appropriate studies.

Experts recommend that NSD1 gene testing should be the initial test [2]. Confirmatory studies such as fluorescence in situ hybridization (FISH) or multiplex ligation-dependent probe amplification (MLPA) are used for identification of microdeletions [1]. Additionally, DNA sequencing is helpful for the detection of mutations.

Prenatal assessment can be offered to affected parents. Testing can be performed on samples derived from chorionic villus sampling (CVS) or amniocentesis.

On bone radiography, most patients will have advanced bone age although this is not a specific test as some patients will have appropriate bone age or delayed growth [6] [9].

Magnetic resonance imaging (MRI) and computed tomography (CT) scanning of the brain may reveal findings such as ventriculomegaly or abnormalities in the trigone and occipital horns [7] [10] [11]. However, these and other anomalies are not specific [11].

  • We report on a male child suffering from repeated LRTIs including bronchitis, pneumonia, and atelectasis during infancy despite inhalations with salbutamol and fluticasone combined with manual chest percussion therapy.[ncbi.nlm.nih.gov]


  • There is limited information on the development of spinal deformity and the need for treatment in this condition. The medical records and spinal radiographs of 5 consecutive patients were reviewed.[ncbi.nlm.nih.gov]
  • Eight patients (19%) presented with scoliosis and seven of them (87.5%) required surgical treatment. The mean follow-up was 9.5 years (range 3-18). Mean age at first consultation was 5.2 years (range 1.1-11.2).[ncbi.nlm.nih.gov]
  • After initiation of dornase alpha inhalations in addition to the current treatment, we observed an improvement in the respiratory symptoms as well as a reduction in the rate of hospitalizations and in the occurrence of LRTIs.[ncbi.nlm.nih.gov]
  • A personalized preventive treatment plan with close supervision of the patient's oral health care is required.[ncbi.nlm.nih.gov]
  • Close family and professional supervision are required to ensure that Sotos syndrome patients receive appropriate dental treatment.[ncbi.nlm.nih.gov]


  • Prognosis of Sotos Syndrome or Cerebral Gigantism This disorder is in no way a life threatening disorder. The abnormalities that a child experiences fade away as the child grows and the motor function that was lost earlier is gained back with time.[epainassist.com]
  • "WHAT IS THE PROGNOSIS?" The good news is that Sotos syndrome is not a life-threatening disorder and patients may have a normal life expectancy.[specialeducationalneeds.co.uk]
  • There aren't biochemical markers for the disease. [10] Treatment [ edit ] Treatment is symptomatic. [10] There is no standard course of treatment for Sotos syndrome. [ citation needed ] Prognosis [ edit ] Sotos syndrome is not a life-threatening disorder[en.wikipedia.org]
  • Prognosis Patients having this kind of diagnosis may have live a life of normal expectancy despite of the fact that it is a non life threatening disorder.[syndromespedia.com]


  • Sotos syndrome is an overgrowth disorder of unknown etiology associated with a high incidence of congenital heart defects. Of 60 patients with Sotos syndrome treated in our hospital, 6 had congenital heart defects.[ncbi.nlm.nih.gov]
  • When evaluating a pediatric patient for pes planus, delayed walking, and gait problems, the practitioner should consider the entire clinical profile and unusual etiologies.[ncbi.nlm.nih.gov]
  • Based on our findings, we discuss the possible etiology and conclude that it is possible, but so far unproven, that a gene dosage effect of NSD1 may be the major cause.[ncbi.nlm.nih.gov]
  • So·tos syn·drome ( sō'tōs ), [MIM*117550] cerebral gigantism and generalized large muscles in childhood, with mental retardation and defective coordination; of unknown etiology.[medical-dictionary.thefreedictionary.com]
  • Reports from the MHC data base Report from the Questionnaire (PDF) Report from the Observation Chart (PDF) Codes: ICD-10: Q87.3 ORPHA: 821 Estimated occurrence 8:1 000 000 inhabitants Etiology Not completely known.[mun-h-center.se]


  • Epidemiology [ edit ] Incidence is approximately 1 in 14,000 births. [11] See also [ edit ] Perlman syndrome Beckwith-Wiedemann syndrome References [ edit ] "7-foot-tall Broc Brown: Facts". Morning News USA. Retrieved 8 March 2017.[en.wikipedia.org]
  • Epidemiology Sotos syndrome is probably one of the most common overgrowth conditions, after the Beckwith-Wiedemann syndrome. The exact birth prevalence remains unknown. Hundreds of cases are reported.[ncbi.nlm.nih.gov]
  • Epidemiology of pervasive developmental disorders. Pediatric Research, 65 (6), 591–598. CrossRef PubMed Google Scholar Frazier, T. W., Ratliff, K. R., Gruber, C., Zhang, Y., Law, P. A., & Constantino, J. N. (2014).[doi.org]
Sex distribution
Age distribution


  • The pathophysiology is not well known but a common underlying basis between various syndromes (Sotos; Beckwith-Wiedemann; Klippel-Trenaunay) is hypothesised.[moh-it.pure.elsevier.com]
  • As pathophysiology regarding abnormalities of NSD1 protein remains unknown, further functional studies are necessary. Key concepts Haploinsufficiency of NSD1 causes Sotos syndrome. Sotos syndrome is a genomic disorder.[els.net]


  • A personalized preventive treatment plan with close supervision of the patient's oral health care is required.[ncbi.nlm.nih.gov]
  • Clinical and laboratory examinations should be performed to prevent and manage any unusual medical aspect of the syndrome. Facial gestalt and macrocephaly, rather than advanced bone age, are the strongest indications for clinical diagnosis.[ncbi.nlm.nih.gov]
  • If premolars are missing, proper preventive and restorative care is necessary to maintain the deciduous molars. Copyright 2009 Wiley-Liss, Inc.[ncbi.nlm.nih.gov]
  • Ongoing surveillance is key to prevent future complications. How do you Prevent Sotos Syndrome? Sotos syndrome is genetic; hence one cannot prevent it .[medindia.net]
  • Her newborn screening results did not make it back in time to prevent the crisis, and no one at our local hospital was familiar with the disease. They did not know how to treat her.[ggc.org]



  1. Baujat G, Cormier-Daire V. Sotos syndrome. Orphanet Journal of Rare Diseases. 2007;2:36.
  2. Tatton-Brown K, Rahman N. Sotos syndrome. Eur J Hum Genet. 2007;15(3):264-271.
  3. Cole TRP, Hughes HE. Sotos syndrome: a study of the diagnostic criteria and natural history. J Med Genet. 1994;31(1):20–32.
  4. Winship I. Sotos syndrome – autosomal dominance inheritance substantiated. Clin Genet. 1985;28(3):243–246.
  5. Agwu JC, Shaw NJ, Kirk J, et al. Growth in Sotos syndrome. Arch Dis Child. 1999;80(4):339–342.
  6. Tatton-Brown K, Douglas J, Coleman K, et al. Childhood Overgrowth Collaboration Genotype-phenotype associations in Sotos syndrome: an analysis of 266 individuals with NSD1 aberrations. Am J Hum Genet. 2005;77(2):193–204.
  7. Cohen MM. Mental deficiency, alterations in performance, and CNS abnormalities in overgrowth syndromes. Am J Med Genet. 2003;117C(1):49–56.
  8. Cole TRP. Congenital urological anomalies in Sotos syndrome. Br J Urol. 1996;78(1):156.
  9. Tatton-Brown K, Rahman N. Clinical features of NSD1-positive Sotos syndrome. Clin Dysmorphol. 2004;13(4):199–204.
  10. Aoki N, Oikawa A, Sakai T. Serial neuroimaging findings in Sotos syndrome. Am J Med Genet. Neurol Res. 1998;20(2):149-152.
  11. Shaefer GB, Bodensteiner JB, Buehler BA, Lin A, Cole TR. The neuroimaging findings in Sotos syndrome. Am J Med Genet. 1997;68(4):571–576.

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Last updated: 2019-06-28 12:28