Background: Lamb-Shaffer is a rare genetic syndrome with just 113 reported cases caused by SOX5 gene haploinsufficiency and disrupts the normal development of cartilage and the nervous system. It can cause an array of clinical features, including craniofacial abnormalities, intellectual disability, global developmental delay, ophthalmological abnormalities, and lesser-known behavioural disturbances. is a case report of ADHD and DMDD in Lamb-Shaffer syndrome, its presentation, and management. Case Report: A 7-year-old male patient presented to the clinic with hyperactivity and difficulty learning. He had a history of motor and language milestone delay, which led to genetic testing, and he was ultimately diagnosed with Lamb-Shaffer syndrome 2 years ago. The patient went to special needs school and had early access to physical, occupational, and speech therapies along with multiple trials of stimulant and non-stimulant medications, which led to adverse effects and failed to effectively help with behavioural and academic challenges. Neuropsychological assessment revealed significant cognitive impairment with a full-scale IQ of 57. The patient was ultimately diagnosed with disruptive mood dysregulation disorder (DMDD) and attention deficit hyperactivity disorder (ADHD), co-existing with Lamb-Shaffer syndrome. Treatment modifications included adjusting Viloxazine, introducing Clonidine, and planning to initiate Aripiprazole, alongside GeneSight genetic testing to optimize medication management. Conclusion: Management of Lamb-Shaffer is complex, especially with behavioural co-morbidities, and requires a multi-disciplinary approach. In our case, the patient failed multiple stimulant and non-stimulant medications, which prompts the importance of more longitudinal and long-term research for Lamb-Shaffer syndrome and behavioural co-morbidities and a need for individualized treatment.
