Clinical presentation and diagnosis of tuberous sclerosis complex in infancy

The age-dependent nature of the characteristic features of tuberous sclerosis complex has historically presented challenges for the diagnosis in infancy. Although the increasing availability of neuroimaging and genetic testing has facilitated the diagnosis in neonates and infants, there are few reports describing how tuberous sclerosis complex presents in this age group. We performed a retrospective review of children diagnosed with tuberous sclerosis complex during the first year of life, compiling their clinical features at presentation and diagnosis, seizure history, and imaging findings. We identified 41 infants diagnosed with tuberous sclerosis complex before age 1 year. Their age at initial presentation ranged from antenatal to 9 months of age. Twenty-three patients (56%) initially presented with a cardiac rhabdomyoma, of which 15 were identified antenatally. Fourteen patients (34%) initially presented with seizures, and 6 (15%) initially presented with hypomelanotic macules. Five infants (12%) had a family history of tuberous sclerosis complex. A definitive diagnosis of tuberous sclerosis complex was accomplished antenatally in 4 patients, whereas the rest were diagnosed at a median age of 2 months. All 41 patients underwent neuroimaging during infancy; 36 (88%) had radiographic evidence of cortical tubers, and 38 (93%) had subependymal nodules. Neuroimaging resulted in a definitive diagnosis of tuberous sclerosis complex in 95% of patients. The diagnosis of tuberous sclerosis complex in infancy is aided by a high index of suspicion and timely access to neuroimaging. Early diagnosis of tuberous sclerosis complex may be essential to the success of future therapies by providing a window of opportunity for their use.