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a pattern of symptoms indicative of some disease
a complex of concurrent things; "every word has a syndrome of meanings"

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(疾患の徴候となる一群の)症徴候,症候群 / (事件・社会的状態などのパターンを示す)徴候形態
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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/05/23 06:49:47」(JST)

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WAGR syndrome is a rare genetic syndrome in which affected children are predisposed to develop Wilms tumour (a tumour of the kidneys), Aniridia (absence of the coloured part of the eye, the iris), Genitourinary anomalies, and Retardation.^[1] The G is sometimes instead given as "gonadoblastoma," since the genitourinary anomalies are tumours of the gonads (testes or ovaries).^[2]

A subset of WAGR syndrome patients shows severe childhood obesity; the acronym WAGRO (O for obesity) has been used to describe this category.^[3]

The condition results from a deletion on chromosome 11 resulting in the loss of several genes. As such, it is one of the best studied examples of a condition caused by loss of neighbouring (contiguous) genes.^[3]

Synonyms

WAGR complex, Wilms tumour-aniridia syndrome, aniridia-Wilms tumour syndrome.

Clinical features and diagnosis

Newborn children with WAGR syndrome are soon noted to have aniridia. The clinical suspicion for WAGR may be increased with the presence of other genital anomalies, though genitourinary anomalies are not always present, particularly in girls.

In older children, clinical diagnosis of the syndrome can be made when aniridia and one of the other features are present. While aniridia is rarely absent in WAGR syndrome, cases have been reported without it. Chromosomal analysis is necessary for definitive diagnosis.^[1]^[4] Other common eye defects include cataracts and ptosis. About 50% of patients develop Wilms' tumour.

Treatment

Children with WAGR syndrome receive regular (3-4 monthly) kidney surveillance for Wilms' tumour until at least the age of 6–8 years and thereafter remain under some follow-up because of the risk of late onset nephropathy (40% of patients over the age of 12 years). Females with WAGR syndrome may have streak ovaries, which can increase the risk for gonadoblastoma. Malformations of the vagina and/or uterus may also be present.

Disease mechanism

WAGR syndrome is caused by a mutation on chromosome 11 in the 11p13 region.^[3] Specifically, several genes in this area are deleted, including the PAX6 ocular development gene and the Wilms' tumour gene (WT1).^[5] Abnormalities in WT1 may also cause genitourinary anomalies. Mutations in the PAX6 gene have recently been shown to not only cause ocular abnormalities, but also problems in the brain and pancreas.^[5]^[6]^[7]^[8]

The gene for brain-derived neurotrophic factor (BDNF), located on 11p14.1, has been proposed as a candidate gene for the obesity and excessive eating in a subset of WAGR patients.^[9] This strengthens the case for a role for BDNF in energy balance.

History

WAGR syndrome was first described by Miller et al. in 1964.^[10]

References

^ ^a ^b Fischbach BV, Trout KL, Lewis J, Luis CA, Sika M (2005). "WAGR syndrome: a clinical review of 54 cases". Pediatrics 116 (4): 984–8. doi:10.1542/peds.2004-0467. PMID 16199712.
^ Clericuzio CL (2004). "WAGR syndrome". In Cassidy SB, Allanson JE. Management of Genetic Syndromes (2nd ed.). New York, NY: John Wiley & Sons. ISBN 0-471-30870-6.
^ ^a ^b ^c Online 'Mendelian Inheritance in Man' (OMIM) WAGR syndrome -194072
^ Turleau C, de Grouchy J, Nihoul-Fékété C, Dufier J, Chavin-Colin F, Junien C (1984). "Del11p13/nephroblastoma without aniridia". Hum Genet 67 (4): 455–6. doi:10.1007/BF00291410. PMID 6092262.
^ ^a ^b Glaser T, Jepeal L, Edwards J, Young S, Favor J, Maas R (1994). "PAX6 gene dosage effect in a family with congenital cataracts, aniridia, anophthalmia and central nervous system defects". Nat Genet 7 (4): 463–71. doi:10.1038/ng0894-463. PMID 7951315.
^ Yasuda T, Kajimoto Y, Fujitani Y, Watada H, Yamamoto S, Watarai T, Umayahara Y, Matsuhisa M, Gorogawa S, Kuwayama Y, Tano Y, Yamasaki Y, Hori M (2002). "PAX6 mutation as a genetic factor common to aniridia and glucose intolerance". Diabetes 51 (1): 224–30. doi:10.2337/diabetes.51.1.224. PMID 11756345.
^ Mitchell T, Free S, Williamson K, Stevens J, Churchill A, Hanson I, Shorvon S, Moore A, van Heyningen V, Sisodiya S (2003). "Polymicrogyria and absence of pineal gland due to PAX6 mutation". Ann Neurol 53 (5): 658–63. doi:10.1002/ana.10576. PMID 12731001.
^ Talamillo A, Quinn J, Collinson J, Caric D, Price D, West J, Hill R (2003). "Pax6 regulates regional development and neuronal migration in the cerebral cortex". Dev Biol 255 (1): 151–63. doi:10.1016/S0012-1606(02)00046-5. PMID 12618140.
^ Han JC, Liu QR, Jones M, et al. (August 2008). "Brain-derived neurotrophic factor and obesity in the WAGR syndrome". N. Engl. J. Med. 359 (9): 918–27. doi:10.1056/NEJMoa0801119. PMC 2553704. PMID 18753648.
^ Miller RW, Fraumeni JF, Manning MD (1964). "Association of Wilms's tumour with aniridia, hemihypertrophy and other congenital malformations". N Engl J Med 270 (18): 922–7. doi:10.1056/NEJM196404302701802. PMID 14114111.

External links

International WAGR Syndrome Association
DECIPHER database entry for WAGR syndrome

UpToDate Contents

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1. ウィルムス腫瘍の症状、診断、および病期分類 presentation diagnosis and staging of wilms tumor
2. 微細欠失症候群（1番～11番染色体） microdeletion syndromes chromosomes 1 to 11
3. ゲノム疾患：概要 genomic disorders an overview
4. ウィルムス腫瘍の治療および予後 treatment and prognosis of wilms tumor
5. 非定型生殖器（性分化疾患）を有する乳児の評価 evaluation of the infant with atypical genitalia disorder of sex development

English Journal

Pineal hypoplasia, reduced melatonin and sleep disturbance in patients with PAX6 haploinsufficiency.

Hanish AE1,2,3, Butman JA4, Thomas F4, Yao J4, Han JC1.
Journal of sleep research.J Sleep Res.2015 Oct 6. doi: 10.1111/jsr.12345. [Epub ahead of print]
In rodent studies, paired box 6 (PAX6) appears to play an important role in the development of the pineal, the primary source of the circadian regulating hormone, melatonin. Pineal hypoplasia has been previously reported in patients with PAX6 haploinsufficiency (+/-); however, pineal measurement, me
PMID 26439359

A Case of WAGR Syndrome with Peters' Anomaly.

von Weissenfluh C1, Gerber-Hollbach N1, Früh B2, August P3, Goldblum D1.
Klinische Monatsblätter für Augenheilkunde.Klin Monbl Augenheilkd.2015 Apr;232(4):382-3. doi: 10.1055/s-0034-1396329. Epub 2015 Apr 22.
PMID 25902081

Common genetic and epigenetic syndromes.

Adams DJ1, Clark DA2.
Pediatric clinics of North America.Pediatr Clin North Am.2015 Apr;62(2):411-26. doi: 10.1016/j.pcl.2014.11.005. Epub 2015 Jan 22.
Cytogenetic anomalies should be considered in individuals with multiple congenital anomalies. DNA methylation analysis is the most sensitive initial test in evaluating for Prader-Willi and Angelman syndromes. The timely identification of cytogenetic anomalies allows for prompt initiation of early in
PMID 25836705

Japanese Journal

P-209A 遺伝子異常と小児悪性腫瘍 : WAGR syndrome2症例の経験(腫瘍3, 第44回日本小児外科学会学術集会)

岩谷さおり,藤原利男,土岡丘,薄井佳子,砂川正勝
日本小児外科学会雑誌 43(3), 541, 2007-05-20
NAID 110006399104

WAGRおよびBeckwith-Wiedemann症候群に発生した片側性Wilms腫瘍に対する腎温存術の経験

福里吉充,大浜用克,武浩志,村上徹,北河徳彦,大矢知昇,工藤博典,気賀澤寿人,田中祐吉,相田典子
小児がん : 小児悪性腫瘍研究会記録 41(2), 280-284, 2004-10-05
… 片側性Wilms腫瘍を合併した,WAGR症候群1例,Beckwith-Wiedemann症候群(BWS)1例に対して腎温存腫瘍切除術(腎温存術)を施行した.腎温存術後の腎機能温存は1例にのみ可能であったが,両症例とも再発なく生存している.WAGRやBWSは,高率にWilms腫瘍を合併する病態であり,両側性Wilms腫瘍に準じた外科的治療が必要と考える. …
NAID 110007170829

定期フォロー中に肉眼的血尿よりWilms腫瘍が発見されたWAGR症候群の1例

盛武浩,満木ひとみ,日高文郎,外山誠也,上村幸代,此元隆雄,園田徹,金子安比古,布井博幸
小児がん : 小児悪性腫瘍研究会記録 41(1), 130-133, 2004-05-30
… WAGR症候群の1歳女児を報告する.3ヵ月毎の腹部超音波による定期フォロー中に肉眼的血尿があり,次いでWilms腫瘍が発見された.腫瘍組織の染色体検査で11p13領域を含む部分欠失が認められた.DNA分析で対側アレルのWT1遺伝子のエクソン7にナンセンス変異を認めた.本症例のようなWilms腫瘍合併頻度の高い症候群では,腹部超音波検査を2歳までは1ヵ月毎に実施するべきであると考えた. …
NAID 110007169877