Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 Iinternational Tuberous Sclerosis Complex Consensus Conference

Abstract

Background: Tuberous sclerosis complex is highly variable in clinical presentation and findings. Disease manifestations continue to develop over the lifetime of an affected individual. Accurate diagnosis is fundamental to implementation of appropriate medical surveillance and treatment. Although significant advances have been made in the past 15 years in the understanding and treatment of tuberous sclerosis complex, current clinical diagnostic criteria have not been critically evaluated or updated since the last clinical consensus conference in 1998.

Methods: The 2012 International Tuberous Sclerosis Complex Consensus Group, comprising 79 specialists from 14 countries, was organized into 12 subcommittees, each led by a clinician with advanced expertise in tuberous sclerosis complex and the relevant medical subspecialty. Each subcommittee focused on a specific disease area with important diagnostic implications and was charged with reviewing prevalence and specificity of disease-associated clinical findings and their impact on suspecting and confirming the diagnosis of tuberous sclerosis complex.

Results: Clinical features of tuberous sclerosis complex continue to be a principal means of diagnosis. Key changes compared with 1998 criteria are the new inclusion of genetic testing results and reducing diagnostic classes from three (possible, probable, and definite) to two (possible, definite). Additional minor changes to specific criterion were made for additional clarification and simplification.

Conclusions: The 2012 International Tuberous Sclerosis Complex Diagnostic Criteria provide current, updated means using best available evidence to establish diagnosis of tuberous sclerosis complex in affected individuals.

Keywords: clinical features; diagnostic criteria; tuberous sclerosis.

FIGURE 1

Three hypopigmented macules the lower back/upper buttocks.

FIGURE 2

Facial angiofibromas.

FIGURE 3

(A) Fibrous plaque on face. (B) Fibrous plaque on scalp.

FIGURE 4

Ungual fibromas.

FIGURE 5

Shagreen patch on dorsolumbar area of back.

FIGURE 6

Dental pits indicated by arrows.

FIGURE 7

Intraoral fibromas (gingival and labial indicated by arrows).

FIGURE 8

Retinal hamartoma indicated by arrow.

FIGURE 9

Retinal achromic patch indicated by arrow.

FIGURE 10

(A) Axial magnetic resonance imaging (MRI) (T2 fluid-attenuated inversion recovery) of the brain, demonstrating cortical dysplasia (tubers and radial migration lines indicated by white and black arrows, respectively). (B) Axial MRI (T1 + contrast) of the brain, demonstrating subependymal nodules (left, two white arrows) and subependymal giant cell astrocytoma (right, black arrow). This patient also has undergone previous partial frontal lobectomy for epilepsy.

FIGURE 11

Echocardiogram indicating cardiac rhabdomyomas (arrows).

FIGURE 12

Axial high-resolution chest computed tomography, demonstrating lymphangioleiomyomatosis.

FIGURE 13

Axial abdominal computed tomography, illustrating multiple bilateral renal angiomyolipomata. The darker areas are fat containing angiomyolipomatous tissue.