The first manifestation in Lamb-Shaffer syndrome is usually motor and language developmental delay in infants and toddlers. As they grow and reach mature adulthood, affected individuals present with variable degrees of intellectual disability (usually ranging from mild to moderate) associated with frequent behavioural disturbances (autism spectrum disorder, stereotypies, isolation, tantrums, and hyperactivity).
Facial characteristics of the syndrome include a broad/full nasal tip, thin upper lip or full lips, a small jaw or chin, a long face, and/or an epicanthus.
Other frequent clinical manifestations associated with Lamb-Shaffer syndrome include hypotonia, small stature or growth retardation, and microcephaly.
Neurological features such as cerebellar ataxia or pyramidal symptoms might be present, although rare.
A subset of patients with SOX5 pathogenic variants (approximately 20%) may present epileptic seizures. These seizures are usually well controlled with anti-epileptic drugs or may occur only once or twice and not require medication.
Eye/vision anomalies are frequent and include strabismus or optic atrophy, and more rarely amblyopia or cortical visual impairment.
Skeletal malformations have been reported in one quarter of patients with SOX5 variants. They include scoliosis, thoracic kyphosis, hip dysplasia and fused cervical vertebrae.
Disorders related to SOX5 genetic alteration are clinically variable with most individuals presenting with mild to moderate disabilities in adulthood but some cases are more severely affected and the reason for this variability is not yet fully understood.
SOX5