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].
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].
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.