Lamb-Shaffer syndrome is a rare autosomal dominant condition. Less than 40 cases have been reported by 2018. Signs and symptoms Clinical features include Global developmental delay Significant speech delay Hypotonia Micrognathia Scoliosis Defects in motor function both fine and gross Optic atrophy Ocular motor apraxia Strabismus Frontal bossing Ear abnormalities Low nasal bridge Epicanthal folds Midline tongue groove Genetics This condition is caused by mutations in the SRY-related HMG-box (SOX5) gene. This gene encodes a protein in the family of transcription factors involved in the regulation of embryonic development and in the determination of the cell fate. The gene is located on the short arm of chromosome 12 (12p12). A study published in 2019 examining 34 families shows that 74% (25/34 families) of the condition are likely to be of de novo occurrence as the variants could not be detected in parental blood samples. In 15% (5/34 families) of the patients the condition was likely inherited from a mosaic parent. In 3% (1/34), the condition was inherited from an affected parent. This means that the majority of the patients have parents who are unaffected whereas inheritance is also possible. Pathogenesis How this mutation causes the clinical picture is not currently clear. Diagnosis The diagnosis may be suspected on the basis of the constellation of clinical features but may only be determined by a genetic test. The full exome sequencing test is used to determine the partial deletion, deletion,or mutation to the SOX5 gene. It is made by sequencing the SOX5 gene responsible for the cells that facilitate information transferring in the brain. Symptoms of Lamb-Shaffer syndrome include fine and gross motor delays, speech delay, global developmental delay,hypotonia and issues with vision, commonly misdiagnosed for autism. Treatment There is currently no curative treatment for this condition. Supportive management is all that is currently available. Epidemiology This is a rare condition with a prevalence of < 1/106. The total number of cases reported to date is <40. History This condition was first described by Lamb et al in 2012 References Genetic diseases and disorders Rare diseases