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].

• Vomiting

  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). [socialstyrelsen.se]

  Since the first month, vomiting, poor weight gain, laryngomalacia with progressive afonic stridor, continuous drooling, and serious feeding problems were evidenced. During lactation, she suffered three episodes of aspiration pneumonia. [nature.com]

  Another common problem is gastroesophageal reflux which causes heartburn, vomiting, esophageal irritation and respiratory problems. [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]

• Advanced Bone Age

  Facial gestalt and macrocephaly, rather than advanced bone age, are the strongest indications for clinical diagnosis. [ncbi.nlm.nih.gov]

• Macrocephaly

  In patients with global developmental delay and concomitant macrocephaly, Sotos syndrome is not uncommon. [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]

  Kids with Sotos syndrome are born with abnormally large heads (macrocrania) and are often taller and heaver throughout the toddler years. They may have a protruding forehead, large hands and feet, and downward-slanting eyes. [kidspot.com.au]

• Large Feet

  […] size Delayed social development Delayed cognitive development Mild mental retardation Speech impairment Down slanting eyes Tallness Large feet Hypertelorism Hypotonia Gum abscesses Unusually large body Delay in developmental milestones Epilepsy Advance [syndromespedia.com]

  During follow up, the facies of Sotos syndrome was noted (fig 5 ) and the hands and feet were large with deep creases in the soles of the feet (fig 6 ). [jmg.bmj.com]

• Aggressive Behavior

  A male Saudi patient, who had a birth length and head circumference above 97th centile, presented with abnormal rapid growth, delayed motor and mental milestones, aggressive behavior, obsession to close doors, nail biting, defective attention, and hyperactivity [ncbi.nlm.nih.gov]

  Mauceri L, Sorge G, Baieli S, Rizzo R, Pavone L, et al. (2000) Aggressive behavior in patients with Sotos syndrome. Pediatric Neurology 22: 64–67. pmid:10669209 View Article PubMed/NCBI Google Scholar 39. [doi.org]

• Compulsive Behavior

  Based on the SRS scores, 65 of the 78 participants (roughly 83 percent) have behaviors associated with autism. These individuals show restricted interests, compulsive behaviors, repetitive speech, social anxiety and reliance on routine. [spectrumnews.org]

• Psychomotor Retardation

  Particular attention to growth parameters to help confirm the presence and extent of developmental delay, psychomotor retardation, and intellectual disability. Echocardiogram to rule out congenital heart defects. [medindia.net]

• Abnormal Behavior

  Both show abnormal behavior and present with long, tapered fingers and toenail defect. No severe congenital malformations were noted. [ncbi.nlm.nih.gov]

• Behavior Problem

  The behavioral problems usually associated with the syndrome include poor social skills, anxiety and/or irritability. Oral findings include prognathism and a high-arched palate with premature eruption of the teeth. [ncbi.nlm.nih.gov]

  People with Sotos syndrome often have intellectual disability, and most also have behavioral problems. [medlineplus.gov]

  Additionally, they may demonstrate behavioral problems such as attention deficit hyperactivity disorder (ADHD) and others. [symptoma.com]

  For example, physical and occupational therapy may help with muscle tone, speech therapy may improve speech, and behavioral assessments may assist with behavioral problems. [encyclopedia.com]

• Hyperactivity

  A male Saudi patient, who had a birth length and head circumference above 97th centile, presented with abnormal rapid growth, delayed motor and mental milestones, aggressive behavior, obsession to close doors, nail biting, defective attention, and hyperactivity [ncbi.nlm.nih.gov]

  Treatment may include: Speech therapy Occupational therapy Behavioral therapy Medications to manage attention-deficit hyperactivity disorder (ADHD), a brain disorder marked by inattention and hyperactivity-impulsivity. [verywellhealth.com]

  Additionally, they may demonstrate behavioral problems such as attention deficit hyperactivity disorder (ADHD) and others. [symptoma.com]

• Clumsiness

  Throughout her life, this child has demonstrated all of the common features of Sotos' syndrome including large size at birth, excessive growth during childhood, dysmorphic craniofacial features, delay in motor and speech development, generalized clumsiness [ncbi.nlm.nih.gov]

  Their size can seem inappropriate for their classroom peers and so very tall children may be labelled as clumsy or aggressive. [childgrowthfoundation.org]

  Clumsiness, an awkward gait, and unusual aggressiveness or irritability may also occur. Although most cases of Sotos syndrome occur sporadically (meaning they are not known to be inherited), familial cases have also been reported. [ninds.nih.gov]

  Such people also may have clumsiness. Even though such cases occur rarely, there have been evidences of a genetic link to it. [epainassist.com]

• Irritability

  After shunt revision, the irritability, sweating and kyphosis improved along with disappearance of the syringomyelia. [ncbi.nlm.nih.gov]

  Treatment options include: behavioral or occupational therapy speech therapy counseling medications to manage ADHD, irritability, or aggressiveness hearing aids for hearing loss glasses to correct vision problems Other treatments may be necessary if you [healthline.com]

  Clumsiness, an awkward gait, and unusual aggressiveness or irritability may also occur. Although most cases of Sotos syndrome occur sporadically (meaning they are not known to be inherited), familial cases have also been reported. [ninds.nih.gov]

  […] problems Kidney and heart problems Individuals may have intellectual impairment and behavioral problems, including: Attention-deficit hyperactivity disorder (ADHD) Obsessive-compulsive disorder (OCD) Impulsive control behaviors Phobias Aggressiveness and irritability [verywellhealth.com]

• Tantrums

  Key themes that emerged in the behavioural literature were overlap with ASD, ADHD, anxiety and high prevalence of aggression/tantrums. [ncbi.nlm.nih.gov]

  Aggression and tantrums Aggressive behaviour and/or tantrums were reported in six studies [ 25, 31, 38, 43 – 45 ] and were assessed through parental report or psychiatric assessment (see Table 3 ). [doi.org]

  […] other symptoms which may comprise of: learning disabilities; delayed motor, cognitive and social development; low muscle tone (hypotonia); speech impairment; and behavioural issues such as attention deficit hyperactivity disorder ( ADHD ), phobias, tantrums [specialeducationalneeds.co.uk]

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].

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]

Read More Read Less Treatment Treatment There is no standard course of treatment for Sotos syndrome. Treatment is symptomatic. Prognosis Prognosis Sotos syndrome is not a life-threatening disorder and patients may have a normal life expectancy. [ninds.nih.gov]

Prognosis Prognosis Sotos syndrome is not a life-threatening disorder and patients may have a normal life expectancy. The initial abnormalities of Sotos syndrome usually resolve as the growth rate becomes normal after the first few years of life. [ninds.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]

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]

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]

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 ] ^ http://www.exploringautism.org/autism/evaluation.htm ^ "7-foot-tall Broc Brown: Facts". [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]

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]

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]

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