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  . Additionally, neonates may present with feeding difficulties, hypotonia, hypoglycemia, and jaundice . Most cases result from NSD1 mutations, of which the majority are sporadic while some are noted to be of autosomal dominant inheritance  . Beckwith-Wiedeman syndrome and Fragile X syndrome are among the differential diagnoses .
Neonates with this overgrowth condition are above average in terms of their weight, length, and occipitofrontal circumference (OFC) . There is a significant growth in the child's first 12 months, which eventually becomes stable . At pubertal age, the growth is appropriate and eventually results in an adult height that falls in the upper range of the normal curve . The OFC remains between 98th and 99.6th percentile throughout the affected individual's life . Moreover, advanced bone age is observed in most patients .
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  . 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 . Additionally, they may demonstrate behavioral problems such as attention deficit hyperactivity disorder (ADHD) and others .
Other manifestations that may be observed in these patients include anomalies of the heart (septal defects) and genitourinary system   . Furthermore, affected children may also manifest with brisk deep tendon reflexes, scoliosis, and seizures   .
Entire Body System
- Advanced Bone Age
Facial gestalt and macrocephaly, rather than advanced bone age, are the strongest indications for clinical diagnosis. [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]
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]
At neurologic examination, central hypotonia and hyperreflexia were detected. She died at the 17th day of live due to respiratory failure. Patient 4. This patient is the second son of unrelated healthy parents. [nature.com]
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 . Confirmatory studies such as fluorescence in situ hybridization (FISH) or multiplex ligation-dependent probe amplification (MLPA) are used for identification of microdeletions . 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.
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   . However, these and other anomalies are not specific .
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