The physical manifestations of<unk>  are due to the formation of hamartia (malformed tissue such as the cortical tubers), hamartomas (benign growths such as facial angiofibroma and subependymal nodules), and very rarely, cancerous hamartoblastomas. The effect of these on the brain leads to neurological symptoms such as seizures, intellectual disability, developmental delay, and behavioral problems. Neurological<unk>  in MRI Three types of brain tumours are associated with<unk> : * Giant cell astrocytoma: (grows and blocks the cerebrospinal fluid flow, leading to dilatation of ventricles causing headache and vomiting) * Cortical tubers: after which the disease is named * Subependymal nodules: form in the walls of ventricles Classic intracranial manifestations of<unk>  include subependymal nodules and cortical/subcortical tubers. The tubers are typically triangular in configuration, with the apex pointed towards the ventricles, and are thought to represent foci of abnormal neuronal migration. The T2 signal abnormalities may subside in adulthood, but will still be visible on histopathological analysis. On magnetic resonance imaging (MRI),<unk>  patients can exhibit other signs consistent with abnormal neuron migration such as radial white matter tracts hyperintense on T2WI and heterotopic grey matter. Subependymal nodules are composed of abnormal, swollen glial cells and bizarre multinucleated cells which are indeterminate for glial or neuronal origin. Interposed neural tissue is not present. These nodules have a tendency to calcify as the patient ages. A nodule that markedly enhances and enlarges over time should be considered suspicious for transformation into a subependymal giant cell astrocytoma, which typically develops in the region of the foramen of Monro, in which case it is at risk of developing an obstructive hydrocephalus. A variable degree of ventricular enlargement is seen, either obstructive (e.g. by a subependymal nodule in the region of the foramen of Monro) or idiopathic in nature. Neuropsychiatric About 90% of people with<unk>  develop a range of neurodevelopmental, behavioural, psychiatric, and psychosocial difficulties. The "TSC‐associated neuropsychiatric disorders" are abbreviated TAND. These difficulties are less frequently identified and thus undertreated when compared with the neurological symptoms. Most problems are associated with more severe intellectual delay or associated with childhood and adolescence, and some (for example depressed mood) may be unreported if the person is unable to communicate. TAND can be investigated and considered at six levels: behavioural, psychiatric, intellectual, academic, neuropsychological, and psychosocial. Behavioural problems most commonly seen include overactivity, impulsivity and sleeping difficulties. Also common are anxiety, mood swings, and severe aggression. Less common are depressed mood, self-injury, and obsessional behaviours. People with<unk>  are frequently also diagnosed with psychiatric disorders: autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), anxiety disorder and depressive disorder.<unk>  is one of the most common genetic causes of autism spectrum disorder, which affects nearly half of people with<unk> . ASD is more common in<unk> 2 than<unk> 1 and more common with earlier and more severe epilepsy, and with lower intellectual ability. ADHD is nearly as frequently seen in<unk>  as ASD (up to half of all people with<unk> . Anxiety and depressive disorders, when they occur, are typically diagnosed in early adulthood and among those intellectually able to express their moods. Schizophrenia (and symptoms like hallucinations or psychosis) is no more common in<unk>  than the general population. The intellectual ability of people with<unk>  varies enormously. About 40–50% have a normal IQ. A normal IQ is much more commonly seen in<unk> 1 than<unk> 2, and profound intellectual disability seen in 34% of<unk> 2 compared with 10% of<unk> 1 in one study. Many studies have examined whether early onset, type and severity of epilepsy associates with intellectual ability. Academic issues occur even in people with<unk>  who have normal intellectual ability. These are often specific learning disorders such as dyscalculia (understanding mathematics), but also include other aspects affecting school life such as anxiety, lack of social skills or low self-esteem. About half of people with<unk> , when assessed for neuropsychological skills, are in the bottom 5th percentile in some areas, which indicates a severe impairment. These include problems with attention (for example, being able to concentrate on two separate things like looking and listening), memory (particularly recall, verbal and spatial working memory) and executive function (for example, planning, self-monitoring, cognitive flexibility). The psychosocial impacts of<unk>  include low self-esteem and self-efficacy in the individual, and a burden on the family coping with a complex and unpredictable disorder. Kidneys Computed tomography showing multiple angiomyolipomas of the kidney in a patient with lung lymphangioleiomyomatosis on CT: suspected<unk>  Between 60 and 80% of<unk>  patients have benign tumors (once thought hamartomatous, but now considered true neoplasms) of the kidneys called angiomyolipomas frequently causing hematuria. These tumors are composed of vascular (angio–), smooth muscle (–myo–), and fat (–lip-) tissue. Although benign, an angiomyolipoma larger than 4 cm is at risk for a potentially catastrophic hemorrhage either spontaneously or with minimal trauma. Angiomyolipomas are found in about one in 300 people without<unk> . However, those are usually solitary, whereas in<unk>  they are commonly multiple and bilateral. About 20-30% of people with<unk>  have renal cysts, causing few problems. However, 2% may also have autosomal dominant polycystic kidney disease. Very rare (< 1%) problems include renal cell carcinoma and oncocytomas (benign adenomatous hamartoma). Lungs Patients with<unk>  can develop progressive replacement of the lung parenchyma with multiple cysts, known as lymphangioleiomyomatosis (LAM). Recent genetic analysis has shown that the proliferative bronchiolar smooth muscle in<unk> -related lymphangioleiomyomatosis is monoclonal metastasis from a coexisting renal angiomyolipoma. Cases of<unk> -related lymphangioleiomyomatosis recurring following lung transplant have been reported. Heart Small tumours of the heart muscle, called cardiac rhabdomyomas, are rare in the general population (perhaps 0.2% of children) but very common in people with<unk> . Around 80% of children under two-years-old with<unk>  have at least one rhabdomyoma, and about 90% of those will have several. The vast majority of children with at least one rhabdomyoma, and nearly all children with multiple rhabdomyomas will be found to have<unk> . Prenatal ultrasound, performed by an obstetric sonographer specializing in cardiology, can detect a rhabdomyoma after 20 weeks. Rhabdomyoma vary in size from a few millimetres to several centimetres, and are usually found in the lower chambers (ventricles) and less often in the upper chambers (atria). They grow in size during the second half of pregnancy, but regress after birth, and are seen in only around 20% of children over two years old. Most rhabdomyomas cause no problems but some may cause heart failure in the foetus or first year of life. Rhabdomyomas are believed to be responsible for the development of heart arrhythmia later in life, which is relatively common in<unk> . Arrhythmia can be hard to spot in people with<unk> , other than by performing routine ECG. For example, arrhythmia may cause fainting that is confused with drop seizures, and symptoms of arrhythmia such as palpitations may not be reported in an individual with developmental delay. Skin Some form of dermatological sign is present in 96% of individuals with<unk> . Most cause no problems, but are helpful in diagnosis. Some cases may cause disfigurement, necessitating treatment. The most common skin abnormalities include: * Hypomelanic macules ("ash leaf spots") are present in about 90% of people with<unk> . These small white or lighter patches of skin may appear anywhere on the body, and are caused by a lack of melanin. They are usually the only visible sign of<unk>  at birth. In fair-skinned individuals, a Wood's lamp (ultraviolet light) may be required to see them. On the scalp, the effect may be a white patch of hair (poliosis). Patches smaller than 3mm are known as "confetti" skin lesions. * Facial angiofibromas are present in about 75% of people with<unk> . These are a rash of reddish spots or bumps on the nose and cheeks in a butterfly distribution, which consist of blood vessels and fibrous tissue. This potentially socially embarrassing rash starts to appear during childhood. * Ungual fibromas: Also known as Koenen's tumors, these are small fleshy tumors that grow around and under the toenails or fingernails. These are rare in childhood, but common by middle age. They are generally more common on toes than on fingers, develop at 15–29 years, and are more common in women than in men. * Fibrous cephalic plaques are present in about 25% of people with<unk> . These are raised, discoloured areas usually found on the forehead, but sometimes on the face or elsewhere on the scalp. * Shagreen patches are present in about half of people with<unk> , appearing in childhood. They are areas of thick leathery skin that are dimpled like an orange peel, and pigmented, they are usually found on the lower back or nape of the neck, or scattered across the trunk or thighs. The frequency of these lesions rises with age. * Dental enamel pits are found in almost all adults with<unk> . * Intraoral fibromas are small surface-tumours found in the gums, inside the cheeks or tongue. Gum (gingival) fibromas are found in about 20-50% of people with<unk> ,
Tuberous sclerosis
Sugarman syndrome
Krabbe disease
Neurofibromatosis
Neurofibromatosis type 4
Neurofibromatosis type I
Neurofibromatosis type II
Leschke syndrome