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Overview

Sotos syndrome is inherited in an autosomal dominant pattern. It is characterised by pre- and postnatal overgrowth, a variable learning disability and distinctive facial appearance.

Clinical features

Growth

  • pre- and postnatal overgrowth (height and/or head circumference two standard deviations above the mean), with peak growth velocity occurring in early childhood; and
  • advanced bone age.

Neurodevelopmental

  • intellectual disability (mild to severe);
  • neonatal hypotonia; and
  • hyperlaxity.

Distinctive facial appearance (most evident in early childhood)

  • prominent jaw;
  • long, narrow face with pointed chin; and
  • down-slanting palpebral fissures.

Other features

  • cardiac and renal anomalies;
  • seizures;
  • scoliosis;
  • strabismus and/or astigmatism;
  • neonatal jaundice and poor feeding; and
  • tumours, including sacrococcygeal teratoma, neuroblastoma, presacral ganglioglioma and acute lymphoblastic leukaemia – though these occur rarely and routine screening is not currently recommended.

Genetics

Sotos syndrome is caused by genetic variants (missense, splicing, nonsense and frameshift) and large deletions in the NSD1 gene (located at chromosome 5q35). The NSD1 gene provides instructions for making a protein (histone methyltransferase) involved in the modification of chromatin, which determines gene expression essential for normal growth and development.

For information about testing, see Presentation: Child with a suspected overgrowth-intellectual disability syndrome and Presentation: Child with macrocephaly.

Inheritance and genomic counselling

Sotos syndrome is an autosomal dominant condition caused by a pathogenic variant in one copy of the NSD1 gene. Most cases (95%) occur de novo (for the first time) in the child.

Where blood tests do not identify the pathogenic variant in either parent, the chance of recurrence is low (under 1%). The chance remains slightly above that of the background population due to the small possibility of constitutional (germline) mosaicism.

Around 5% of cases have an affected parent, in which case the chance of recurrence in future pregnancies is 50%.

Families should be offered counselling by the local clinical genetics service in advance of future conception.

Management

Management of children with Sotos syndrome should be delivered via a multidisciplinary team. Suggested approaches have been published by several authors.

Guidelines may include echocardiogram and ultrasound scan, ophthalmology and audiology assessments and developmental support. Routine cancer screening is not currently recommended. Please see recommended management guidance resources in the list below.

Resources

For clinicians

For patients

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  • Last reviewed: 19/03/2023
  • Next review due: 19/03/2025
  • Authors: Dr Maria Gogou
  • Reviewers: Dr Elaine Clark, Dr Ellie Hay, Dr Terri McVeigh