<unk>  complex is diagnosed with clinical and genetic tests. There are many different mutations in the<unk> 1 and<unk> 2 genes that have been identified in individuals with<unk> . A pathogenic mutation in the gene prevents the proteins from being made or inactivates the proteins. If such a pathogenic mutation is found then this alone is sufficient to diagnose<unk> . However, some mutations are less clear in their effect, and so not sufficient alone for diagnosis. Between 1 in 10 and 1 in 4 of individuals with<unk>  have no mutation that can be identified. Once a particular mutation is identified in someone with<unk> , this mutation can be used to make confident diagnoses in other family members. For clinical diagnosis, there isn't one sign that is unique (pathognomonic) to<unk> , nor are all signs seen in all individuals. Therefore, several signs are considered together, classed as either major or minor features. An individual with two major features, or one major feature and at least two minor features can be given a definite diagnosis of<unk> . If only one major feature or at least two minor features are present, the diagnosis is only regarded as possibly<unk> . + Diagnostic Criteria for<unk>  Complex Major Features Location Sign Onset Note 1 Skin Hypomelanotic macules Infant – child At least three, at least 5 mm in diameter. 2 Head Facial angiofibromas or fibrous cephalic plaque Infant – adult At least three angiofibromas 3 Fingers and toes Ungual fibroma Adolescent – adult At least two 4 Skin Shagreen patch (connective tissue nevus) Child 5 Eyes Multiple retinal nodular hamartomas Infant 6 Brain Cortical dysplasias Fetus (includes tubers and cerebral white matter radial migration lines) 7 Brain Subependymal nodule Child – adolescent 8 Brain Subependymal giant cell astrocytoma Child – adolescent 9 Heart Cardiac rhabdomyoma Fetus 10 Lungs Lymphangioleiomyomatosis Adolescent – adult 11 Kidneys Renal angiomyolipoma Child – adult At least two. Together, 10 and 11 count as one major feature. Minor Features Location Sign Note 1 Skin "Confetti" skin lesions 2 Teeth Dental enamel pits At least three 3 Gums Intraoral fibromas At least two 4 Eyes Retinal achromic patch 5 Kidneys Multiple renal cysts 6 Liver, spleen and other organs Nonrenal hamartoma<unk>  can be first diagnosed at any stage of life. Prenatal diagnosis is possible by chance if heart tumours are discovered during routine ultrasound. In infancy, epilepsy, particularly infantile spasms, or developmental delay may lead to neurological tests. The white patches on the skin may also first become noticed. In childhood, behavioural problems and autism spectrum disorder may provoke a diagnosis. During adolescence, the skin problems appear. In adulthood, kidney and lung problems may develop. An individual may also be diagnosed at any time as a result of genetic testing of family members of another affected person.
Tuberous sclerosis
Sugarman syndrome
Krabbe disease
Neurofibromatosis
Neurofibromatosis type 4
Neurofibromatosis type I
Neurofibromatosis type II
Leschke syndrome