Sotos syndrome

This is part of Rare diseases.

Diagnosis: Sotos syndrome

Synonyms: Cerebral gigantism


Date of publication: 2014-10-08
Version: 2.0

ICD 10 code


The disease

Sotos syndrome is characterized by excessive physical growth, a characteristic appearance and varying degrees of cognitive disability. Another name is cerebral gigantism, referring to the brain's role in the syndrome.

The syndrome was identified for the first time in the 1930s, but was named after Professor Juan Sotos, who in 1964 described five unusually tall children in the United States who shared a similar, characteristic appearance.


Slightly more than 200 people with Sotos syndrome have been described in international medical literature, but the precise incidence is unknown. In Sweden it is estimated that between five and ten children are born annually with the condition and approximately one hundred people have been diagnosed with the disease. As knowledge of the condition improves, it is increasingly possible to arrive at more exact numbers of children with the syndrome.


Most people with Sotos syndrome have a mutation on gene NSD1, located on the long arm of chromosome 5 (5q35). Among other things, gene NSD1 is believed to regulate the activity of certain other genes involved in growth and development.

In some cases chromosomal translocation (where genetic material has changed places) has been identified between chromosomes 5 and other chromosomes.


The syndrome is usually caused by a new mutation. This means that the genetic mutation occurs in an individual for the first time and is not inherited from either parent. Consequently, parents with a child with a new mutation generally have only a slight risk of having another child with the disorder. However, the new genetic mutation will be hereditary and an adult with this mutation risks passing on the mutated gene to his/her children.

There are families where more than one member has the syndrome. In these instances, the most common inheritance pattern is autosomal dominant. This means that one of the parents has the disease, and so has one normal gene and one mutated gene. Sons and daughters of this parent have a 50 per cent risk of inheriting the disease. Children who do not inherit the mutated gene do not have the disease and do not pass it down.

Figure: Autosomal dominant inheritance


Children with Sotos syndrome are already large at birth and have larger heads, hands and feet than their peers. Neo-natal jaundice, hypotonia (low muscle tone) and feeding problems including vomiting and sucking difficulties, are common. Some newborns show symptoms of low blood sugar (hypoglycaemia).

Characteristic facial features including a high, protuberant forehead, widely spaced eyes, a long, large head and a pointed chin, are especially noticeable during the first six or seven years of life.

The mouth and teeth

The palate is often high. Teeth usually appear early, although this varies between individuals. One or more tooth buds may be absent so teeth fail to show. There may be abnormalities in dental enamel. Anatomical abnormalities in the nose and oral cavity in combination with lax muscle tone can cause the individual to breathe through his/her mouth. This may result in snoring or in sleep apnea (a sleep disorder characterized by abnormal pauses in breathing). Oral motor skills may be under-developed leading to chewing difficulties and unclear speech. Drooling is very common.


Although children with Sotos syndrome are considerably taller than others of the same age, research has shown that their pre-pubescence is characterized by low rather than elevated levels of growth hormone. A possible explanation for this rapid increase in height may be an abnormal sensitivity to growth hormone in the relevant cell receptors. The height of the children often leads people to assume they are much older than they are and to make unrealistic demands of them. Accelerated growth slows in puberty but children often remain taller than their peers. As adults, people with Sotos syndrome remain tall.


Most children with Sotos syndrome experience delayed motor development, balance and coordination problems, and muscle tone (tonus) is reduced. Learning, language and concentration difficulties are also common, as is mild to moderate cognitive impairment. Behavioural problems include those typical of autism, as well as periodic aggression, hyperactivity and sleeping problems. Many children have poor self-confidence and are socially retiring.

Other points

During their first years, children are often susceptible to infection. Conductive hearing loss as a result of abnormalities in the middle ear may occur. This may also be caused by recurrent upper respiratory and ear infections.

Convulsions are common, and a minority of children with the syndrome develop epilepsy. Some children have heart defects, although they usually do not require surgical intervention. Reduced thyroid activity and increased perspiration levels have also been described.

Eye abnormalities occur, usually in the form of long-sightedness, but also include involuntary eye movements (nystagmus) and squinting (strabismus).

Curvature of the spine (scoliosis) is also relatively common, as are flat feet. Some people with the syndrome have thin, brittle nails.

Some children have abnormalities of the urinary tract in the form of vesicoureteral reflux, an abnormal movement of urine from the bladder back into the ureters. Some slightly older children may have problems with constipation, and with faecal incontinence.

The syndrome slightly increases the risk of the child developing tumours in the nervous system, kidneys, skeleton and salivary glands and in adults, an increased risk of tumours in the liver, skin and internal sex organs.


The diagnosis is made on the basis of particular, typical signs. The syndrome is associated with early skeletal maturity in relation to age, a large head and characteristic facial features. It is more difficult to arrive at a diagnosis in adults than children as the characteristic facial features which make the symptom easily recognizable become less prominent with age. MRI and computed tomography (CT) brain scans show no definite changes, although slight widening of the ventricles of the brain may occur. DNA-based diagnosis is possible.

Currently, Sotos syndrome is a differential diagnosis, meaning that it is made when other disorders with similar symptoms have been eliminated. Some diagnoses with similar symptoms are Weaver syndrome, Beckwith-Wiedemann syndrome and Fragile X syndrome. Separate information on these diseases is available in the rare disease database of the Swedish National Board of Health and Welfare.

At the time of diagnosis it is important that the family is offered genetic counselling. Carrier and prenatal diagnosis, as well as pre-implantation genetic diagnosis (PGD) in association with IVF (in vitro fertilization), are available to families where the mutation is known.


There is no cure for the syndrome, but symptoms can be relieved in various ways. Much can be done to support the individual and compensate as much as possible for functional limitations.

The heart and kidneys should be examined to discover and treat possible abnormalities.

The eyes should be examined in order to detect and treat eye symptoms. Children usually require glasses to correct long sightedness.

Mild hearing loss as a result of fluid in the middle ear can be treated by a grommet, a small plastic tube inserted through the ear drum. Devices to improve hearing, such as hearing aids, may be required and should be tried out at an early stage.

At an early stage an orthodontist should look for possible dental aplasia (missing teeth) and other bite abnormalities. Most children with the syndrome require additional preventative dental care in the form of fluoride treatment and help with oral hygiene.


Early habilitation is essential to stimulate the child's development and help compensate for functional limitations. A habilitation team includes professionals with special expertise in how disability affects everyday life, health and development. Help is available within the medical, educational, psychological, social and technical fields. Habilitation may include assessments, treatment, assistance with choice of aids, information about disabilities and counselling. Information is also given about support offered by public services as well as advice on the way accommodation and other environments can be adapted to the child’s needs. The whole family should be offered support. The family may also need help coordinating interventions.

Reduced muscle tone and problems with balance and coordination should be assessed and treated by a physiotherapist. This applies also to lax muscle tone in the joints and curvature of the spine. Motor skills, balance and coordination can improve with the help of different forms of physical exercise. Flat feet may need to be treated by arch supports or special shoes.

Speech therapists (language pathologists) assess language and speech so that children receive early language stimulation and training. Complementary methods of communication may be necessary for the person to participate fully in different social situations. For children with a cognitive impairment it is very important that their speech development is stimulated at an early age by Augmentative and Alternative Communication (ACC), a form of communication which is not speech-based.

A speech therapist assesses and treats chewing and swallowing problems, and drooling.

So that the correct form of specialist educational help and resources can be offered, it is important that the right information is provided to the school. For children with a cognitive impairment, support may be offered in special classes. Behavioural abnormalities including aggression, concentration difficulties and behaviour associated with autism mean that children and their families may require support from a psychologist, social worker and specialist teacher.

Adults with the syndrome who have a cognitive impairment require continued, individual support from adult habilitation services in their daily lives. This may take the form of support and care in accommodation with special services and daily activities.

Practical advice

In Norway, Frambu Senter for sjeldne funksjonshemninger has information Sotos syndrome which includes practical hints: www.frambu.no.

National and regional resources in Sweden

Specialists with knowledge of Sotos syndrome are located at The Queen Silvia Children's Hospital, SE-416 85 Gothenburg, Sweden. Tel: +46 31 343 40 00.

Specialists in orofacial problems are located at Mun-H-Center, Institute of Odontology, Medicinaregatan 12A, SE-413 90 Gothenburg, Sweden. Tel: +46 31 750 92 00, email: mun-h-center@vgregion.se, www.mun-h-center.se.

Resource personnel

Senior Physician in paediatric neurology and habilitation Barbro Westerberg, The Queen Silvia Children's Hospital, SE-416 85 Gothenburg, Sweden.Tel: +46 31 343 40 00, email: barbro.westerberg@vgregion.se.

Courses, exchanges of experience, recreation

Ågrenska is a national competence centre for rare diseases and its families' programme arranges stays for children and young people with disabilities and their families. Ågrenska is open to families from the whole of Sweden and focuses particularly on the needs of children and young people with rare diseases. In addition, a number of programmes every year are provided for adults with rare diseases. Information is available from Ågrenska, Box 2058, SE-436 02 Hovås, Sweden. Tel: +46 31 750 91 00, fax: +46 31 91 19 79, email: agrenska@agrenska.se, www.agrenska.se. The Swedish Sotos Association is involved in planning, and may help in providing, some of the content when required.

Organizations for the disabled/patient associations 

The Swedish Sotos Association, Chairperson: Stig-Olof Schönfeldt, Jakthyddan 3, SE-892 42 Domsjö, Sweden. Tel: +46 660 535 82, www.sotos.se.

Rare Diseases Sweden, Sturegatan 4A, Box 1386, SE-172 27 Sundbyberg, Sweden. Tel: +46 8 764 49 99, email: info@sallsyntadiagnoser.se, www.sallsyntadiagnoser.se. Rare Diseases Sweden is a national association representing people with rare diseases and varying disabilities.

FUB, The Swedish National Association for Children, Young People and Adults with Intellectual Disabilities, Industrivägen 7 (visitors address), Box 1181, 171 23 Solna, Sweden. Tel: +46 8 508 866 00, fax: +46 8 508 866 66, email: fub@fub.se, www.fub.se.

The Autism and Asperger Association, Bellmansgatan 30, SE-118 47 Stockholm, Sweden. Tel: +46 8 702 05 80, email: info@autism.se, www.autism.se.

Courses, exchanges of experience for personnel

During the weeks of the Ågrenska Family Program, training days are organized for personnel working with the children who are participating. Information is available from Ågrenska, Box 2058, SE-436 02 Hovås, Sweden. Tel: +46 31 750 91 00, fax: +46 31 91 19 79, email: agrenska@agrenska.se, www.agrenska.se. The Swedish Sotos Association is involved in planning, and may help in providing, some of the content when required.

Research and development

Research into genetic varieties of Sotos syndrome is carried out at Uppsala University. Research is also under way at The Queen Silvia Children's Hospital in Gothenburg, primarily into hormonal abnormalities associated with the syndrome.

Information material

Short summaries of all the database texts are available as leaflets, in Swedish only. They can be printed out or ordered by selecting the Swedish version, and then clicking on the leaflet icon which will appear under, "Mer hos oss" in the column on the right-hand side.

Newsletters from Ågrenska on Sotos syndrome, no. 289 (2007) and no. 312, (2008). (In Swedish only.) These newsletters are edited summaries of lectures delivered at family and adult stays at Ågrenska. They may be ordered from Ågrenska, Box 2058, SE-436 02 Hovås, Sweden. Tel: +46 31 750 91 00, fax: +46 31 91 19 79, email: agrenska@agrenska.se. They are also available at www.agrenska.se.

Information can be ordered from the Swedish Sotos Association. (See address under "Organizations for the disabled/patient associations etc".)

  • Sotos Syndrom – en handbok för familjer (in Swedish only).
  • Att leva med Sotos syndrom – a DVD film from 1998 about three children with Sotos syndrome (in Swedish only).

In Norway, the website of Frambu Senter for sjeldne funksjonshemninger contains information on Sotos syndrome, and it is possible to order further material (in Norwegian only), www.frambu.no.


De Boer L, Kant SG, Karperien M, van Beers L, Tjon J, Vink GR et al. Psychosocial, cognitive and motor dysfunctioning in patients with suspected Sotos syndrome: a comparison genotype-phenotype correlation in patients suspected of having Sotos syndrome. Horm Res 2004; 62: 197-207.

Faravelli F. NSD1 mutations in Sotos syndrome. Am J Med Genet C Semin Med Genet 2005; 137: 24-31.

Fryssira H, Drossatou P, Sklavou R, Barambouti F, Manolaki N. Two cases of Sotos syndrome with novel mutations of the NSD1 gene. Genet Couns 2010; 21: 53-59.

van Haelst MM, Hoogeboom JJ, Bayjat G, Brüggenwirth HT, Van de Laar I, Coleman K et al. Familial gigantism caused by an NSD1 mutation. Am J Med Genet 2005; 139: 40-44.

Hughes HE. Sotos syndrome: a study of the diagnostic criteria and natural history. J Med Genet 1994; 31: 20-32.

Kurotaki N, Harada N, Shimokawa O, Miyake N, Kawame H, Uetake K et al. Fifty microdeletions among 112 cases of Sotos syndrome: Low copy repeats possibly mediate the common deletion. Hum Mutat 2003; 22: 378-387.

Lapunzina P. Risk of tumorigenesis in overgrowth syndromes: a comprehensive review. Am J Med Genet C Semin Med Genet 2005; 137: 53-71.

Leventopoulos G, Kitsiou-Tzeli S, Kritikos K, Psoni S, Mavrou A, Kanavakis E, Fryssira H. A clinical study of Sotos syndrome patients with review of the literature. Pediatr Neurol 2009; 40: 357-364.

Mussa A, Chiesa N, Porta F, Baldassarre G, Silengo MC, Ferrero GB. The overlap between Sotos and Beckwith-Wiedemann syndromes. J Pediatr 2010; 156: 1035-1036.

Rutter SC, Cole TR. Psychological characteristics of Sotos syndrome. Dev Medicine and Child Neurology 1991; 33: 898-902.

Schaefer GB, Bodensteiner JB, Buehler BA, Lin A, Cole TR. The neuroimaging findings in Sotos syndrome. Am J Med Genet 1997; 11: 462-465.

Sotos JF, Dodge PR, Murihead D, Crawford JD, Talbot NB. Cerebral gigantism in childhood: a syndrome of excessively rapid growth with acromegalic features and a nonprogressive neurologic disorder. New Eng J Med 1964; 271: 109-116.

Tatton-Brown K, Douglas J, Coleman K, Baujat G, Cole TR, Das S. Childhood overgrowth collaboration. Genotype-phenotype associations in Sotos syndrome: an analysis of 266 individuals with NSD1 aberrations. Am J Hum Genet 2005; 77: 193-204.

Visser R, Landman EB, Goeman J, Wit JM, Karperien M. Sotos syndrome is associated with deregulation of the MAPK/ERK-signaling pathway. PLoS One 2012; 7: e49229.

Visser R, Matsumoto N. Genetics of Sotos syndrome. Curr Opin Pediatr 2003; 15: 598-606.

Wit JM, Beemer FA, Barth PG, Oorthuys JW, Dijkstra PF, Van den Brande JL, Leshot NJ et al. Cerebral gigantism (Sotos syndrome). Compiled data of 22 cases. Eur J Pediatr 1985; 144: 131-140.

Database references

OMIM (Online Mendelian Inheritance in Man)
Search: cerebral gigantism

GeneReviews (University of Washington)
Search: Sotos syndrome

Orphanet (European database)
Search: Sotos syndrome

Document information

The Swedish Information Centre for Rare Diseases produced and edited this information material.

The medical expert who wrote the draft of this information material is Senior Physician Barbro Westerberg, The Queen Silvia Children's Hospital, Gothenburg, Sweden.

The relevant organizations for the disabled/patient associations have been given the opportunity to comment on the content of the text.

An expert group on rare diseases, affiliated with the University of Gothenburg, approved the material prior to publication.

Date of publication: 2014-10-08
Version: 2.0
Publication date of the Swedish version: 2014-04-15

For enquiries contact The Swedish Information Centre for Rare Diseases, The Sahlgrenska Academy at the University of Gothenburg, Box 422, SE-405 30 Gothenburg, Sweden. Tel: +46 31 786 55 90, email: ovanligadiagnoser@gu.se.


About the database

This knowledge database provides information on rare diseases and conditions. The information is not intended to be a substitute for professional medical care, nor is it intended to be used as a basis for diagnosis or treatment.