Bourneville disease

結節性硬化症、ブルヌヴィーユ・プリングル病、ブルヌヴィーユ病

WordNet

1. an impairment of health or a condition of abnormal functioning
2. caused by or altered by or manifesting disease or pathology; "diseased tonsils"; "a morbid growth"; "pathologic tissue"; "pathological bodily processes" (同)morbid, pathologic, pathological

PrepTutorEJDIC

1. (体の)『病気』,疾患 / (精神・道徳などの)病気,病弊
2. 女性の話術芸人 =diseur
3. 病気にかかった / 病的な,不健全な(morbid)

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/07/10 17:07:57」(JST)

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Not to be confused with tuberculosis.

Tuberous sclerosis
Classification and external resources
A case of tuberous sclerosis showing facial angiofibromas in characteristic butterfly pattern
ICD-10	Q85.1
ICD-9	759.5
OMIM	191100
DiseasesDB	13433
MedlinePlus	000787
eMedicine	neuro/386 derm/438 ped/2796 radio/723
MeSH	D014402

Tuberous sclerosis or tuberous sclerosis complex (TSC) is a rare multi-system genetic disease that causes non-malignant tumors to grow in the brain and on other vital organs such as the kidneys, heart, eyes, lungs, and skin. A combination of symptoms may include seizures, developmental delay, behavioral problems, skin abnormalities, lung and kidney disease. TSC is caused by a mutation of either of two genes, TSC1 and TSC2, which code for the proteins hamartin and tuberin respectively. These proteins act as tumor growth suppressors, agents that regulate cell proliferation and differentiation.

The name, composed of the Latin tuber (swelling) and the Greek skleros (hard), refers to the pathological finding of thick, firm and pale gyri, called "tubers," in the brains of patients postmortem. These tubers were first described by Désiré-Magloire Bourneville in 1880; the cortical manifestations may sometimes still be known by the eponym Bourneville's disease.

Signs and symptoms

See also: List of dental abnormalities associated with cutaneous conditions

The physical manifestations of tuberous sclerosis 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, mental retardation, developmental delay and behavioral problems. Symptoms also include trouble in school and concentration problems.

Central nervous system

Tuberous sclerosis in MRI.

About 50% of people with TSC have learning difficulties ranging from mild to significant, and studies have reported that between 25% and 61% of affected individuals meet the diagnostic criteria for autism, with an even higher proportion showing features of a broader pervasive developmental disorder. A 2008 study reported self-injurious behavior in 10% of people with TSC. Other conditions, such as ADHD, aggression, behavioral outbursts and OCD can also occur. Lower IQ is associated with more brain involvement on MRI.

Three types of brain tumours may be associated with TSC:

• Giant cell astrocytoma: (grows and blocks the CSF flow leading to dilatation of ventricles causing headache and vomiting)
• Cortical tubers: after which the disease is named.
• Sub-ependymal nodules: form in the walls of ventricles.

Classic intracranial manifestations of tuberous sclerosis 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, TSC patients can exhibit other signs consistent with abnormal neuron migration (radial white matter tracts hyperintense on T2WI, heterotopic gray matter).

Subependymal nodules are composed of abnormal, swollen glial cells and bizarre multinucleated cells which are indeterminate for glial or neuronal origin. There is no interposed neural tissue. 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 (SEGA). A SEGA 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, either obstructive (e.g. by a subependymal nodule in the region of the foramen of Monro) or idiopathic in nature.

Kidneys

Computed tomography showing multiple angiomyolipomas of the kidney in a patient with lung lymphangioleiomyomatosis on CT: suspected tuberous sclerosis.

Between 60 and 80% of TSC patients have benign tumors (once thought hamartomatous, but now considered true neoplasms) of the kidneys called angiomyolipomas (AML) frequently causing hematuria. These tumors are composed of vascular tissue (angio–), smooth muscle (–myo–), and fat (–lipoma). Although benign, an AML larger than 4 cm is at risk for a potentially catastrophic hemorrhage either spontaneously or with minimal trauma. AMLs are found in about 1 in 300 people without TSC. However, those are usually solitary, whereas in TSC they are commonly multiple and bilateral.

Approximately 20-30% of people with TSC will 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 TSC can develop progressive replacement of the lung parenchyma with multiple cysts. This process is identical to another disease called lymphangioleiomyomatosis (LAM). Recent genetic analysis has shown that the proliferative bronchiolar smooth muscle in tuberous sclerosis-related LAM is monoclonal metastasis from a coexisting renal angiomyolipoma. There have been cases of TSC-related LAM recurring following lung transplant.

Heart

Rhabdomyomas are benign tumors of striated muscle. A cardiac rhabdomyoma can be discovered using echocardiography in approximately 50% of people with TSC. However, the incidence in the newborn may be as high as 90% and in adults as low as 20%. These tumors grow during the second half of pregnancy and regress after birth. Many will disappear entirely. Alternatively, the tumor size remains constant as the heart grows, which has much the same effect.

Problems due to rhabdomyomas include obstruction, arrhythmia and a murmur. Such complications occur almost exclusively during pregnancy or within the child's first year.

Prenatal ultrasound, performed by an obstetric sonographer specializing in cardiology, can detect a rhabdomyoma after 20 weeks. This rare tumour is a strong indicator of TSC in the child, especially if there is a family history of TSC.

Skin

Some form of dermatological sign will be present in 96% of individuals with TSC. Most cause no problems but are helpful in diagnosis. Some cases may cause disfigurement, necessitating treatment. The most common skin abnormalities include:

• Facial angiofibromas ("adenoma sebaceum"): A rash of reddish spots or bumps, which appear on the nose and cheeks in a butterfly distribution. They consist of blood vessels and fibrous tissue. This socially embarrassing rash starts to appear during childhood and can be removed using dermabrasion or laser treatment.
• Periungual fibromas: Also known as Koenen's tumors, these are small fleshy tumors that grow around and under the toenails or fingernails and may need to be surgically removed if they enlarge or cause bleeding. These are very 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. They can be induced by nail-bed trauma.
• Hypomelanic macules ("ash leaf spots"): White or lighter patches of skin that may appear anywhere on the body and are caused by a lack of melanin. These are usually the only visible sign of TSC at birth. In fair-skinned individuals a Wood's lamp (ultraviolet light) may be required to see them.
• Forehead plaques: Raised, discolored areas on the forehead.
• Shagreen patches: Areas of thick leathery skin that are dimpled like an orange peel,pigmented and usually found on the lower back or nape of the neck. They can also be scattered across the trunk or thighs. The frequency of these lesions rises with age.
• Other skin features are not unique to individuals with TSC, including molluscum fibrosum or skin tags, which typically occur across the back of the neck and shoulders, café au lait spots or flat brown marks, and poliosis, a tuft or patch of white hair on the scalp or eyelids.

Eyes

Retinal lesions, called astrocytic hamartomas (or "phakomas"), which appear as a greyish or yellowish-white lesion in the back of the globe on the ophthalmic examination. Astrocytic hamartomas can calcify, and they are in the differential diagnosis of a calcified globe mass on a CT scan.

Non-retinal lesions associated with TSC include

• Coloboma
• Angiofibromas of the eyelids
• Papilledema (related to hydrocephalus)

Variability

Individuals with tuberous sclerosis may experience none or all of the clinical signs discussed above. The following table shows the prevalence of some of the clinical signs in individuals diagnosed with tuberous sclerosis.

The frequency of clinical signs in children with tuberous sclerosis, grouped by age

Genetics

Tuberous sclerosis is inherited in an autosomal dominant fashion.

Tuberous sclerosis is a genetic disorder with an autosomal dominant pattern of inheritance, variable expressivity, and incomplete penetrance. Two thirds of TSC cases result from sporadic genetic mutations, not inheritance, but their offspring may inherit it from them. Current genetic tests have difficulty locating the mutation in approximately 20% of individuals diagnosed with the disease. So far it has been mapped to two genetic loci, TSC1 and TSC2.

TSC1 encodes for the protein hamartin, is located on chromosome 9 q34 and was discovered in 1997. TSC2 encodes for the protein Tuberin, is located on chromosome 16 p13.3 and was discovered in 1993. TSC2 is contiguous with PKD1, the gene involved in one form of polycystic kidney disease (PKD). Gross deletions affecting both genes may account for the 2% of individuals with TSC who also develop PKD in childhood. TSC2 has been associated with a more severe form of TSC. However, the difference is subtle and cannot be used to identify the mutation clinically. Estimates of the proportion of TSC caused by TSC2 range from 55% to 80-90%.

TSC1 and TSC2 are both tumor suppressor genes that function according to Knudson's "two hit" hypothesis. That is, a second random mutation must occur before a tumor can develop. This explains why, despite its 100 percent penetrance, TSC has wide expressivity.

Hamartin Identifiers Symbol TSC1 Entrez 7248 HUGO 12362 OMIM 605284 RefSeq NM_000368 UniProt Q92574 Other data Locus Chr. 9 q34

Tuberin Identifiers Symbol TSC2 Entrez 7249 HUGO 12363 OMIM 191092 RefSeq NM_000548 UniProt P49815 Other data Locus Chr. 16 p13.3

Pathophysiology

Hamartin and tuberin function as a complex which is involved in the control of cell growth and cell division. (The complex appears to interact with Rheb GTPase, thus sequestering it from activating mTOR signalling, part of the growth factor (insulin) signalling pathway.) Thus, mutations at the TSC1 and TSC2 loci result in a loss of control of cell growth and cell division, and therefore a predisposition to forming tumors. TSC affects tissues from different germ layers. Cutaneous and visceral lesions may occur, including adenoma sebaceum, cardiac rhabdomyomas, and renal angiomyolipomas. The central nervous system (CNS) lesions seen in this disorder include hamartomas of the cortex, hamartomas of the ventricular walls, and subependymal giant cell tumors, which typically develop in the vicinity of the foramina of Monro.

Molecular genetic studies have defined at least two loci for TSC. In TSC1, the abnormality is localized on chromosome 9q34, but the nature of the gene protein, called hamartin, remains unclear. No missense mutations occur in TSC1. In TSC2, the gene abnormalities are on chromosome 16p13. This gene encodes tuberin, a guanosine triphosphatase–activating protein. The specific function of this protein is unknown. In TSC2, all types of mutations have been reported; new mutations occur frequently. Few differences have yet been observed in the clinical phenotypes of patients with mutation of one gene or the other.

Diagnosis

There are no pathognomonic clinical signs for tuberous sclerosis. Many signs are present in individuals who are healthy (although rarely), or who have another disease. A combination of signs, classified as major or minor, is required in order to establish a clinical diagnosis.

Diagnostic Criteria for Tuberous Sclerosis Complex

Major Features
	Location	Sign	Onset	Note
1	Head	Facial angiofibromas or forehead plaque	Infant – adult
2	Fingers and toes	Nontraumatic ungual or periungual fibroma	Adolescent – adult
3	Skin	Hypomelanotic macules	Infant – child	More than three.
4	Skin	Shagreen patch (connective tissue nevus)	Child
5	Brain	Cortical tuber	Fetus
6	Brain	Subependymal nodule	Child – adolescent
7	Brain	Subependymal giant cell astrocytoma	Child – adolescent
8	Eyes	Multiple retinal nodular hamartomas	Infant
9	Heart	Cardiac rhabdomyoma	Fetus	Single or multiple.
10	Lungs	Lymphangioleiomyomatosis	Adolescent – adult
11	Kidneys	Renal angiomyolipoma	Child – adult	10 and 11 together count as one major feature.
Minor Features
	Location	Sign	Note
12	Teeth	Multiple randomly distributed pits in dental enamel
13	Rectum	Hamartomatous rectal polyps	Histologic confirmation is suggested.
14	Bones	Bone cysts
15	Brain	Cerebral white-matter "migration tracts"	Radiographic confirmation is sufficient. 5 and 15 together count as one major feature.
16	Gums	Gingival fibromas
17	Liver, spleen and other organs	Nonrenal hamartoma	Histologic confirmation is suggested.
18	Eyes	Retinal achromic patch
19	Skin	"Confetti" skin lesions
20	Kidneys	Multiple renal cysts	Histologic confirmation is suggested.

In infants, the first clue is often the presence of seizures, delayed development or white patches on the skin. A full clinical diagnosis involves

• Taking a personal and family history.
• Examining the skin under a Wood's lamp (hypomelanotic macules), the fingers and toes (ungual fibroma), the face (angiofibromas) and the mouth (dental pits and gingival fibromas).
• Cranial imaging with non enhanced CT or, preferably, MRI (cortical tubers and subependymal nodules).
• Renal ultrasound (angiomyolipoma or cysts).
• An echocardiogram in infants (rhabdomyoma).
• Fundoscopy (retinal nodular hamartomas or achromic patch).

The various signs are then marked against the diagnostic criteria to produce a level of diagnostic certainty:

• Definite – Either two major features or one major feature plus two minor features.
• Probable – One major plus one minor feature.
• Suspect – Either one major feature or two or more minor features.

Due to the wide variety of mutations leading to TSC, there are no simple genetic tests available to identify new cases. Nor are there any biochemical markers for the gene defects. However, once a person has been clinically diagnosed, the genetic mutation can usually be found. The search is time-consuming and has a 15% failure rate, which is thought to be due to somatic mosaicism. If successful, this information can be used to identify affected family members, including prenatal diagnosis. As of 2006, preimplantation diagnosis is not widely available.

Management

Drug therapy for some of the manifestations of TSC is currently in the developmental stage. For example, a 2008 study found that treatment with rapamycin rescued learning and memory deficits in a mouse model of tuberous sclerosis. Community TSC is a distributed computing project to find drugs to treat TSC.^{[citation needed]} The patients usually have relapse of symptoms in the clinical course. Unless any vital function is affected, life expectancy is good. Majority of patients will require some medications to control symptoms, e.g., anti-epileptics to control seizures. In 2010 everolimus was approved for the treatment of subependymal giant cell astrocytoma.

Other drugs used include:

• Vigabatrin
• ACTH

Prognosis

The prognosis for individuals with TSC depends on the severity of symptoms, which range from mild skin abnormalities to varying degrees of learning disabilities and epilepsy to severe mental retardation, uncontrollable seizures, and kidney failure. Those individuals with mild symptoms generally do well and live long productive lives, while individuals with the more severe form may have serious disabilities. However, with appropriate medical care, most individuals with the disorder can look forward to normal life expectancy.

A study of 30 TSC patients in Egypt found that "...earlier age of seizures commencement (<6 months) is associated with poor seizure outcome and poor intellectual capabilities. Infantile spasms and severely epileptogenic EEG patterns are related to the poor seizure outcome, poor intellectual capabilities and autistic behavior. Higher tubers numbers is associated with poor seizure outcome and autistic behavior. Left sided tuber burden is associated with poor intellect, while frontal location is more encountered in ASD. So, close follow up for the mental development and early control of seizures are recommended in a trial to reduce the risk factors of poor outcome. Also early diagnosis of autism will allow for earlier treatment and the potential for better outcome for children with TSC."

Leading causes of death include renal disease, brain tumour, lymphangiomyomatosis of the lung, and status epilepticus or bronchopneumonia in those with severe mental handicap. Cardiac failure due to rhabdomyomas is a risk in the fetus or neonate, but is rarely a problem subsequently. Kidney complications such as angiomyolipoma (AML) and cysts are common, and more frequent in females than males and in TSC2 than TSC1. Renal cell carcinoma is uncommon. Lymphangioleiomyomatosis (LAM) is only a risk for females with AMLs. In the brain, the subependymal nodules occasionally degenerate to subependymal giant cell astrocytomas (SEGA). These may block the circulation of cerebrospinal fluid around the brain, leading to hydrocephalus.

Detection of the disease should prompt one for genetic counselling. It is also important to know that even though the disease does not have a cure, symptoms can be treated symptomatically. Hence, awareness regarding different organ manifestations of tuberous sclerosis is important.

Epidemiology

Tuberous sclerosis occurs in all races and ethnic groups, and in both genders. The live-birth prevalence is estimated to be between 10 and 16 cases per 100,000. A 1998 study estimated total population prevalence between about 7 and 12 cases per 100,000, with more than half of these cases undetected. These estimates are significantly higher than those produced by older studies, when tuberous sclerosis was regarded as an extremely rare disease. The reason is that the invention of CT and ultrasound scanning have enabled the diagnosis of many non-symptomatic cases. Prior to this, the diagnosis of tuberous sclerosis was largely restricted to severely affected individuals with Vogt's triad of learning disability, seizures and facial angiofibroma. The total population prevalence figures have steadily increased from 1:150,000 in 1956, to 1:100,000 in 1968, to 1:70,000 in 1971, to 1:34,200 in 1984, to the present figure of 1:12,500 in 1998. Whilst still regarded as a rare disease, it is common when compared to many other genetic diseases.

History

Main article: Timeline of tuberous sclerosis

Désiré-Magloire Bourneville

Tuberous sclerosis first came to medical attention when dermatologists described the distinctive facial rash (1835 and 1850). A more complete case was presented by von Recklinghausen (1862) who identified heart and brain tumours in a newborn that had only briefly lived. However, Bourneville (1880) is credited with having first characterized the disease, coining the name tuberous sclerosis, thus earning the eponym Bourneville's disease. The neurologist Vogt (1908) established a diagnostic triad of epilepsy, idiocy, and adenoma sebaceum (an obsolete term for facial angiofibroma).

Symptoms were periodically added to the clinical picture. The disease as presently understood was first fully described by Gomez (1979). The invention of medical ultrasound, CT and MRI has allowed physicians to examine the internal organs of live patients and greatly improved diagnostic ability.

Two genetic loci associated with tuberous sclerosis, TSC1 and TSC2, were discovered in 1997 and 1992 respectively. This has enabled the use of genetic testing as a diagnostic tool. The proteins associated with TSC1 and TSC2, harmartin and tuberin, function as a complex in the mTOR signalling pathway that controls cell growth and cell division. The importance of this pathway in cancer therapy has stimulated further research into Tuberous Sclerosis.

In 2002, treatment with rapamycin was found to be effective at shrinking tumours in animals. This has led to human trials of rapamycin as a drug to treat several of the tumors associated with Tuberous Sclerosis.

References

External links

• tuberous-sclerosis at NIH/UW GeneTests
• GeneReview/NCBI/NIH/UW entry on Tuberous Sclerosis Complex
• The Tuberous Sclerosis Alliance in the United States offers a comprehensive Web site, online discussion groups, and free publications.
• The HUGO Gene Nomenclature Committee web pages for TSC1 and TSC2 provide a selection of links for further genetic research.
• The Rothberg Institute For Childhood Diseases have a distributed computing project called CommunityTSC
• Dermatlas: Images of Tuberous sclerosis
• Mass General Hospital's Living with TSC
• The Tuberous Sclerosis Association in the UK has a comprehensive Web site
• Cancer.Net: Tuberous Sclerosis Syndrome

UpToDate Contents

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• 1. 結節性硬化症：遺伝学、臨床的特徴、および診断 tuberous sclerosis complex genetics clinical features and diagnosis
• 2. 結節性硬化症：管理 tuberous sclerosis complex management
• 3. 結節性硬化症の腎症状 renal manifestations of tuberous sclerosis complex
• 4. 結節性硬化症複合体（TSC）における肺病変 pulmonary involvement in tuberous sclerosis complex
• 5. 腎血管筋脂肪腫 renal angiomyolipomas

English Journal

• Everolimus improves memory and learning while worsening depressive- and anxiety-like behavior in an animal model of depression.

• Russo E1, Leo A2, Crupi R3, Aiello R2, Lippiello P4, Spiga R5, Chimirri S2, Citraro R2, Cuzzocrea S3, Constanti A6, De Sarro G2.
• Journal of psychiatric research.J Psychiatr Res.2016 Jul;78:1-10. doi: 10.1016/j.jpsychires.2016.03.008. Epub 2016 Mar 19.
• Everolimus (EVR) is an orally-administered rapamycin analog that selectively inhibits the mammalian target of rapamycin (mTOR) kinase (mainly mTORC1 and likely mTORC2) and the related signaling pathway. mTOR is a serine/threonine protein kinase regulating multiple important cellular functions; dysfu
• PMID 27019134

• Rapamycin requires AMPK activity and p27 expression for promoting autophagy-dependent Tsc2-null cell survival.

• Campos T1, Ziehe J1, Fuentes-Villalobos F1, Riquelme O1, Peña D1, Troncoso R2, Lavandero S3, Morin V1, Pincheira R1, Castro AF4.
• Biochimica et biophysica acta.Biochim Biophys Acta.2016 Jun;1863(6 Pt A):1200-7. doi: 10.1016/j.bbamcr.2016.03.009. Epub 2016 Mar 11.
• Tuberous sclerosis complex (TSC) disease results from inactivation of the TSC1 or TSC2 gene, and is characterized by benign tumors in several organs. Because TSC tumorigenesis correlates with hyperactivation of mTORC1, current therapies focus on mTORC1 inhibition with rapamycin or its analogs. Rapam
• PMID 26975583

• Expression of microRNAs miR21, miR146a, and miR155 in tuberous sclerosis complex cortical tubers and their regulation in human astrocytes and SEGA-derived cell cultures.

• van Scheppingen J1, Iyer AM1, Prabowo AS1, Mühlebner A1,2, Anink JJ1, Scholl T2, Feucht M2, Jansen FE3, Spliet WG4, Krsek P5, Zamecnik J6, Buccoliero AM7, Giordano F8, Genitori L8, Kotulska K9, Jozwiak S10, Jaworski J11, Liszewska E11, van Vliet EA1, Aronica E1,12,13.
• Glia.Glia.2016 Jun;64(6):1066-82. doi: 10.1002/glia.22983. Epub 2016 Mar 25.
• Tuberous sclerosis complex (TSC) is a genetic disease presenting with multiple neurological symptoms including epilepsy, mental retardation, and autism. Abnormal activation of various inflammatory pathways has been observed in astrocytes in brain lesions associated with TSC. Increasing evidence supp
• PMID 27014996

Japanese Journal

• 老研究者の覚え書 順天堂時代I : 心筋疾患(1) 心筋炎後心拡大症、拘束型心筋症、進行性筋ディストロフィ症心、特発性心筋疾患と類縁心疾患、分娩後心疾患と関連心疾患、肥大型心筋症

• 岡田 了三
• 群馬パース大学紀要 6, 135-170, 2008-03
• … その第1回のテーマとして肥大型心筋症(HCM)の病理所見を整理して4型に分類した:(I)Noonan HOCM 型、(II)LEOP-ARD心尖閉塞ApH(O)CM型、(Ill)Braunwald(Bourneville)大動脈弁下IHSS型、(IV)Fabry非閉塞中隔肥厚ASH型。 …
• NAID 110007044998

• 頻発するてんかん発作を伴う結節性硬化症を合併した小児の全身麻酔

• 三村 真一郎,木倉 睦人,板垣 大雅 [他]
• 麻酔 55(4), 471-474, 2006-04
• NAID 40007254686

Related Links

• Bourneville's disease | definition of Bourneville's disease by ...

sclerosis [sklĕ-ro´sis] an induration or hardening, especially of a part from inflammation, or in disease of the interstitial substance. The term is used chiefly for such a hardening of the nervous system due to hyperplasia of the ...

• Bourneville disease - RightDiagnosis.com - Right Diagnosis

Bourneville disease symptoms, causes, diagnosis, and treatment information for Bourneville disease (Tuberous sclerosis) with alternative diagnoses, full-text book chapters, misdiagnosis, research treatments, prevention, and ...

Related Pictures

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★リンクテーブル★

リンク元	「結節性硬化症」
関連記事	「disease」

「結節性硬化症」

　　[★]

英

tuberous sclerosis, TSC

同

ブルヌヴィーユ病 Bourneville's disease Bourneville disease、ブルヌヴィーユ母斑症(NDE)、ブルヌヴィーユ・プリングル病 ブルヌヴィーユ-プリングル病 Bourneville-Pringle disease、ブルヌヴィーユ・プリングル母斑症(NDE)、結節性脳硬化症 tuberous brain sclerosis

関

神経皮膚症候群、網膜神経膠性過誤腫

概念

• 神経皮膚症候群の一種
• 3主徴：精神遅滞、てんかん、顔面の血管線維腫(皮脂腺腫)

疫学

• 孤発例：60-70 (NDE.345)
• 頻度：1人/1万-15万人 (参考3)

病因

• 特発性
• 遺伝性：TSC1(9q34)、TSC2(16p13.3)

遺伝形式

• 常染色体優性遺伝

病理

• 大脳皮質、網膜に星状膠細胞性過誤腫 astrocytic hamartoma (NDE.345)

症候

• 神経：

• てんかん発作(生後半年以内に初発(参考3))。発作型はウエスト症候群、レノックス・ガストー症候群が多い
• 精神遅滞

• 皮膚：

• 幼児期の葉状白斑(70%以上の例で新生児期に出現(参考3))
• 幼児期以降に多発する鼻周囲の丘疹(血管線維腫)
• 隆起革様皮膚
• 爪囲線維腫(Koenen腫瘍) (NDE.345)

• 心臓：筋腫
• 腎臓：血管筋脂肪腫、腎嚢胞
• 肺
• 手指：爪下線維腫

検査

頭部CT

• 側脳室壁や基底核での結節状石灰沈着、脳室拡大 (NDE.345)

• 脳室壁に沿った石灰化(candle guttering / brain stone)

頭部MRI

• 結節状腫瘤 (NDE.345)
• T2強調画像：大脳皮質下の斑状高信号領域

治療

• 皮膚
• てんかん(痙攣発作)
• 進行性知能低下：治療法無し

参考

• 1. 皮膚症状 写真

http://www.nagata-microtia.jp/images/100628214139.jpg

• 2. [charged] Tuberous sclerosis complex - uptodate [1]
• 3.

http://i-erika.com/room/bohansyo_1.html

同

血管線維腫

「disease」

　　[★]

• n.

疾患：illnessより厳密な概念。「ある臓器に明確な障害が確認され、それによって症状が出ているとはっきり説明できる場合」 (PSY.9)

特定の原因、病態生理、症状、経過、予後、病理組織所見が全てそろった場合 (PSY.9)

• something that is very wrong with people's attitudes, way of life or with society.

関

ail、ailment、disease entity、disorder、ill、illness、malady、sick、sickness

• 注意

disease ≠ illness ≠ disorder