Handbook of Genetic Counseling/Sotos Syndrome
- 1 Introduction
- 2 Incidence
- 3 Diagnosis
- 4 At birth
- 5 Molecular Genetics and Genetic Testing
- 6 Neuroradiological findings
- 7 Growth and Feeding
- 8 Development, learning, behavior
- 9 Neurological
- 10 Immune system
- 11 Eye problems
- 12 Dental abnormalities (common)
- 13 Heart problems
- 14 Malignant tumors
- 15 Musculoskeletal
- 16 GI
- 17 Main Psychosocial Considerations
- 18 Differential Diagnosis
- 19 Patient resources
- 20 References
- 21 Notes
- Overgrowth syndrome
- etiology still uncertain although researchers in Japan found a gene that may be the cause of Sotos syndrome in a large number of individuals with classical Sotos syndrome (published paper in 2002)
- usually sporadic
- <2% show autosomal dominant inheritance (4 of 200 families, but facial gestalt is different)
- Unknown slightly less common than Beckwith-Wiedemann with prevalence of 1 in 13,700 births
- Diagnosis is clinical
- 4 core features (must have at least 3 of the 4 to really make a diagnosis)
- First 3 features are relative to general population so setting a cutoff is not always clear
- rapid early growth pre and postnatal
- advanced bone age
- developmental delay
- characteristic facial appearance specific to Sotos syndrome
- alters in childhood and adolescence
- in newborn period (macrocephaly, high bossed forehead, dolichocephaly, high palate, appearance suggestive of hypertelorism)
- face lengthens, jaw becomes more prominent, dolichocephaly (tall narrow skull) and frontal bossing (prominent forehead) become more obvious
- delay in growth of hair which is often thin "appearance of receding hairline"
- midchildhood downslant to palpebral fissures, wear and discoloration of teeth, tendency for a rosy coloration of cheeks, chin, and nasal tip.
- All 4 core features are present in at least 75% of true cases of Sotos syndrome and <20% of other specific and nonspecific overgrowth patterns
- Often the presence of a high arched palate, poor suck, and low muscle tone which often produce feeding problems
- Jaundice occurs frequently.
Molecular Genetics and Genetic Testing
- Gene mutation found in a number of Japanese patients with Sotos syndrome
- Located at 5q35 gene named NSD-1
- Lab in Chicago and Germany are doing clinical testing
- Details found at http://www.genes.uchicago.edu/clinic/SotosTest.html
- FISH analysis for NSD1 deletion detection. Mutation analysis is currently being validated for clinical use; please check back on availability.
- No lab listed on GeneClinics doing research testing presently, but lab in UK may be doing research testing
- FISH - 12 days and cost is $325
- NSD1 encodes 2,696 amino acids and may interact with nuclear receptors (NRs)
- expressed in the fetal and adult brain, kidney, skeletal muscle, spleen, and the thymus, and faintly in the lung.
- Among 42 SS patients examined, we detected 4 (10 %) de novo point mutations in NSD1
- In addition, FISH analysis using BAC clones flanking the 5q35 breakpoint revealed submicroscopic deletions involving the entire NSD1 gene in 20 (67%) of 30 patients whose chromosomes were available (Nat Genet 30:365-366, 2002)
- http://caroll.vjf.cnrs.fr/cancergene/CG1830.html discusses the NSD1 protein
- Ventricular abnormalities (prominence of trigone, prominent occipital horns, ventriculomegaly)
- Midline defects and absence or hypoplasia of corpus collosum
Growth and Feeding
- Feeding problems common in neonatal period
- Most LGA (most evident in length and in head circumference)
- Height and head circumference most significantly larger and run parallel to growth curve but sig. above 97th centile
- Excess growth mostly in limbs rather than trunk
- Girls in UK population were an average of 6.2 cm above calculated target height based on parental heights, but were within usual height range
- Boys height less predictable and greater tendency for increased adult stature
Development, learning, behavior
- Almost all have developmental delay and cognitive impairment (may be selection bias because this is used as diagnostic criteria)
- Behavioral problems common
- Poor concentration and ADHD common
- Difficulty with social interactions results in tendency to associate with younger children and social isolation later in life
- Reliance on routines common in many children
- May have impetuous behavior
- Poor sleep patterns common
- Unusual anxiety and subsequent phobias commonly reported
- Hypotonia usually present from birth but improves during childhood
- Poor 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
- Infections very common in early childhood
- Recurrent OM and potential conductive hearing loss
- Urinary tract infections in up to 20% (caused by structural abnormalities and reflux usually)
- poorly documented
- Refractive errors and strabismus (less common, glaucoma and nystagmas reported)
- Regular evaluations
Dental abnormalities (common)
- Early teeth eruption (54%)
- Excessive wear and discoloration
- Teeth may be crooked due to changes in craniofacial structure and many require orthodontic work
(thought to be rare)
- Overt congenital heart disease is thought to be rare may be up to 10%
- Most common are ASD, VSD, PDA
- Routine echo not necessary
(rare, but may occur in approximately 2-4% of individuals with Sotos syndrome)
- Embryonal tumors
- Age of onset is wide and no clear benefit from surveillance
- Hypotonia, large size, joint laxity can cause complications
- Foot deformities (~50%)
- Flat feet common
- Tendency for severe constipation in over 10%
- Intellectual, social, and emotional maturity may evolve on widely different timetables
- How is school going? (confirm that she is in 4th grade and ask specifically about math and language skills)
- Does she have a new IEP since last visit?
- Is she getting the help you would like her to?
- Math tutoring and speech therapy?
- How is attention and behavior?
- Assess social relationships (is she being teased or socially isolated)
- Any changes in the family?
- Confirm number of siblings
- Number of other generalized overgrowth syndromes
- Sotos syndrome is distinguished from others by presence of developmental delay and characteristic facial features.
- Other overgrowth syndromes have other commonly associated characteristics that also aid in distinction
- Soto Syndrome Support Association
- http://www.well.com/user/sssa/ -- website is very updated and contains good accurate information
- Three Danada Square East, #235
- Wheaton, IL 60187
- Genetests and info from Chicago about NSD1 testing
- Soto Syndrome Support Association
- Sotos Syndrome: A Handbook for Families by Rebecca Rae Anderson, M.S., J.D. and Bruce A. Buehler, M.D.
- Kurotaki et al., Haploinsufficiency of NSD1 causes Sotos syndrome (2002) Nature Genetics, 30: 365-366
- Management of Genetic Syndromes. Edited by S.B. Cassidy and J.E. Chapter ___ Sotos syndrome.
Named after Dr Juan F. Sotos who described it in 1964.
The information in this outline was last updated in 2003.