Clinical Presentation and Diagnosis of Tuberous Sclerosis Complex in Infancy

Abstract

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.

Tuberous sclerosis complex in the Western Cape, South Africa: The clinical presentation features

“…The guidelines recommend presymptomatic electroencephalography (EEG) in the age group at risk of epileptic spasms. [2,5] Datta et al [6] (infants only), N=41 Erol et al, [7] Angiomyolipoma,* n (%) 17 (44) 13 (12) 6 (15) 1 (5) Cardiac rhabdomyoma,* n (%) 8 (20) 51 (58) 35 (85) Facial angiofibroma,* n (%) 19 (49) 24 (29) 24 (29) 8 (40) >3 hypomelanotic macules,* n (%) 27 (69) 80 (65) 21 (51) 17 (85) Shagreen patch,* n (%) 10 (28) 30 (24) 30 (73) 2 (10) Ungual and periungual fibroma,* n (%) 1 (0.02) 3 (2) --*International diagnostic criteria. [2] IN PRACTICE While this is a viable intervention at our centre, patients in this study typically had already evolved seizures as a presenting complaint.…”

“…[5][6][7] This may reflect disease behaviour, whereby only the most symptomatic patients access healthcare services in our setting. In SA, there is no effective structure for routine screening of asymptomatic children for TSC.…”

Symptom profiles of autism spectrum disorder in tuberous sclerosis complex

“…2,3 In fact, TSC is one of the most commonly occurring single-gene disorders associated with ASD. [4][5][6] Given the high rate of ASD in TSC and the fact that TSC is often diagnosed in utero or in early infancy, 7 TSC has been considered a model system for understanding mechanisms underlying ASD. [8][9][10][11] However, the specific phenotypic profile of ASD in TSC and the extent to which it converges with nonsyndromic ASD (nsASD) has not been well-established.…”

“Mais-Nadim-Nasser Triad”, A Useful Marker for Leukodystrophies Diagnosis

“…The novelty of this Triad stems from two facts: first, it was not described in the medical literature as a unique clinical tool in the algorithm for diagnosis of white matter diseases, second, being a relatively quick tool for sorting and diagnosis of the group of LD relying on symptoms and signs from which a patient suffers, when the next step will be deliberate to reach the exact name of the disease, by brain MRI and mutation search [9,25,26].…”