The Experts below are selected from a list of 45 Experts worldwide ranked by ideXlab platform
Maki Fukami - One of the best experts on this subject based on the ideXlab platform.
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long term effect of Aromatase inhibition in Aromatase Excess Syndrome
Journal of the Endocrine Society, 2021Co-Authors: Gerhard Binder, Maki Fukami, Tsutomu Ogata, Akie Nakamura, Roland Schweizer, Keisuke NagasakiAbstract:CONTEXT Aromatase Excess Syndrome (AEXS) is a very rare disorder characterized by prepubertal gynecomastia, bone age acceleration, and early growth arrest. Heterozygote submicroscopic rearrangements within the promotor of CYP19A1 result in overexpression of Aromatase and enhanced aromatization of androgens. OBJECTIVE The objective was to study long-term treatment effects of an Aromatase inhibitor. METHODS Data from 7 boys with AEXS were retrospectively collected. Genetic analysis revealed upstream of CYP19A1 a 165 901 bp deletion in 4 German cousins, a 198 662 bp deletion in 2 Japanese brothers, and a 387 622 bp tandem duplication in a Japanese boy. RESULTS All boys developed prepubertal gynecomastia, at median 9.0 years of age (range: 7.0-11.0). Height was +1.20 standard deviation score (SDS) (-0.24 to +1.98); predicted adult height was -1.29 SDS (-3.29 to +1.09). Four boys were treated with 1.0 mg of anastrozole daily, while 3 reached adult height untreated. Treatment with anastrozole was stopped after 5.6 years (4.0-6.8). Three treated boys exceeded their prognosis by 2.4, 6.9, and 8.1 cm, while 1 untreated boy fell below the prognosis by 8.6 cm. One treated with a low dose and 2 untreated reached their prognosis. Adult heights were -0.91 SDS with anastrozole (-2.86 to -0.29) and -0.15 SDS without (-2.31 to -0.03). Distance to target height was -0.22 SDS with anastrozole (-1.72 to +0.52) and +0.54 SDS without (+0.23 to +1.30). CONCLUSION Spontaneous growth in AEXS varied, even in the same family. Our data suggest that early started, long-term inhibition by anastrozole promotes adult height in boys with AEXS.
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understanding the pathological manifestations of Aromatase Excess Syndrome lessons for clinical diagnosis
Expert Review of Endocrinology & Metabolism, 2014Co-Authors: Makio Shozu, Maki Fukami, Tsutomu OgataAbstract:Aromatase Excess Syndrome is characterized by pre- or peripubertal onset of gynecomastia due to estrogen Excess because of a gain-of-function mutation in the Aromatase gene (CYP19A1). Subchromosomal recombination events including duplication, deletion, and inversion has been identified. The latter two recombinations recruit novel promoters for CYP19A1 through a unique mechanism. Gynecomastia continues for life, and although the general condition is well preserved, it may cause psychological issues. Minor symptoms (variably advanced bone age and short adult height), if present, are exclusively because of estrogen Excess. Serum estradiol levels are elevated in 48% of affected males, but are not necessarily useful for diagnosis. Molecular analysis of CYP19A1 mutations is mandatory to confirm Aromatase Excess Syndrome diagnosis. Furthermore, the use of an Aromatase inhibitor can ameliorate gynecomastia.
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Aromatase Excess Syndrome a rare autosomal dominant disorder leading to pre or peri pubertal onset gynecomastia
Pediatric endocrinology reviews, 2014Co-Authors: Maki Fukami, Makio Shozu, Keisuke Nagasaki, Mami Miyado, Tsutomu OgataAbstract:Abstract Overexpression of CYP19A1 encoding Aromatase results in a rare genetic disorder referred to as Aromatase Excess Syndrome (AEXS). Male patients with AEXS manifest pre- or peri-pubertal onset gynecomastia, gonadotropin deficiency, and advanced bone age, while female patients are mostly asymptomatic. To date, 30 male patients with molecularly confirmed AEXS have been reported. A total of 12 types of submicroscopic rearrangements, i.e., two simple duplications, four simple deletions, two simple inversions, and four complex rearrangements, have been implicated in AEXS. Clinical severity of AEXS primarily depends on the types of the rearrangements. AEXS appears to account for a small number of cases of pre- or peri-pubertal onset gynecomastia, and should be suspected particularly when gynecomastia is associated with an autosomal dominant inheritance pattern, characteristic hormone abnormalities and/or advanced bone age. Treatment with an Aromatase inhibitor appears to benefit patients with AEXS, although long-term safety of this class of drugs remains unknown.
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Aromatase Excess Syndrome a rare autosomal dominant disorder leading to pre or peri pubertal onset gynecomastia
Pediatric endocrinology reviews, 2014Co-Authors: Maki Fukami, Makio Shozu, Keisuke Nagasaki, Mami Miyado, Tsutomu OgataAbstract:Abstract Overexpression of CYP19A1 encoding Aromatase results in a rare genetic disorder referred to as Aromatase Excess Syndrome (AEXS). Male patients with AEXS manifest pre- or peri-pubertal onset gynecomastia, gonadotropin deficiency, and advanced bone age, while female patients are mostly asymptomatic. To date, 30 male patients with molecularly confirmed AEXS have been reported. A total of 12 types of submicroscopic rearrangements, i.e., two simple duplications, four simple deletions, two simple inversions, and four complex rearrangements, have been implicated in AEXS. Clinical severity of AEXS primarily depends on the types of the rearrangements. AEXS appears to account for a small number of cases of pre- or peri-pubertal onset gynecomastia, and should be suspected particularly when gynecomastia is associated with an autosomal dominant inheritance pattern, characteristic hormone abnormalities and/or advanced bone age. Treatment with an Aromatase inhibitor appears to benefit patients with AEXS, although long-term safety of this class of drugs remains unknown.
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genomic basis of Aromatase Excess Syndrome recombination and replication mediated rearrangements leading to cyp19a1 overexpression
The Journal of Clinical Endocrinology and Metabolism, 2013Co-Authors: Maki Fukami, Takayoshi Tsuchiya, Heike Vollbach, Kristy A Brown, Shuji Abe, Shigeyuki Ohtsu, Martin Wabitsch, Henry G Burger, Evan R Simpson, Akihiro UmezawaAbstract:Context: Genomic rearrangements at 15q21 have been shown to cause overexpression of CYP19A1 and resultant Aromatase Excess Syndrome (AEXS). However, mutation spectrum, clinical consequences, and underlying mechanisms of these rearrangements remain to be elucidated. Objective: The aim of the study was to clarify such unsolved matters. Design, Setting, and Methods: We characterized six new rearrangements and investigated clinical outcome and local genomic environments of these rearrangements and of three previously reported duplications/deletions. Results: Novel rearrangements included simple duplication involving exons 1–10 of CYP19A1 and simple and complex rearrangements that presumably generated chimeric genes consisting of the coding region of CYP19A1 and promoter-associated exons of neighboring genes. Clinical severities were primarily determined by the copy number of CYP19A1 and the property of the fused promoters. Sequences at the fusion junctions suggested nonallelic homologous recombination, nonhom...
Tsutomu Ogata - One of the best experts on this subject based on the ideXlab platform.
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long term effect of Aromatase inhibition in Aromatase Excess Syndrome
Journal of the Endocrine Society, 2021Co-Authors: Gerhard Binder, Maki Fukami, Tsutomu Ogata, Akie Nakamura, Roland Schweizer, Keisuke NagasakiAbstract:CONTEXT Aromatase Excess Syndrome (AEXS) is a very rare disorder characterized by prepubertal gynecomastia, bone age acceleration, and early growth arrest. Heterozygote submicroscopic rearrangements within the promotor of CYP19A1 result in overexpression of Aromatase and enhanced aromatization of androgens. OBJECTIVE The objective was to study long-term treatment effects of an Aromatase inhibitor. METHODS Data from 7 boys with AEXS were retrospectively collected. Genetic analysis revealed upstream of CYP19A1 a 165 901 bp deletion in 4 German cousins, a 198 662 bp deletion in 2 Japanese brothers, and a 387 622 bp tandem duplication in a Japanese boy. RESULTS All boys developed prepubertal gynecomastia, at median 9.0 years of age (range: 7.0-11.0). Height was +1.20 standard deviation score (SDS) (-0.24 to +1.98); predicted adult height was -1.29 SDS (-3.29 to +1.09). Four boys were treated with 1.0 mg of anastrozole daily, while 3 reached adult height untreated. Treatment with anastrozole was stopped after 5.6 years (4.0-6.8). Three treated boys exceeded their prognosis by 2.4, 6.9, and 8.1 cm, while 1 untreated boy fell below the prognosis by 8.6 cm. One treated with a low dose and 2 untreated reached their prognosis. Adult heights were -0.91 SDS with anastrozole (-2.86 to -0.29) and -0.15 SDS without (-2.31 to -0.03). Distance to target height was -0.22 SDS with anastrozole (-1.72 to +0.52) and +0.54 SDS without (+0.23 to +1.30). CONCLUSION Spontaneous growth in AEXS varied, even in the same family. Our data suggest that early started, long-term inhibition by anastrozole promotes adult height in boys with AEXS.
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understanding the pathological manifestations of Aromatase Excess Syndrome lessons for clinical diagnosis
Expert Review of Endocrinology & Metabolism, 2014Co-Authors: Makio Shozu, Maki Fukami, Tsutomu OgataAbstract:Aromatase Excess Syndrome is characterized by pre- or peripubertal onset of gynecomastia due to estrogen Excess because of a gain-of-function mutation in the Aromatase gene (CYP19A1). Subchromosomal recombination events including duplication, deletion, and inversion has been identified. The latter two recombinations recruit novel promoters for CYP19A1 through a unique mechanism. Gynecomastia continues for life, and although the general condition is well preserved, it may cause psychological issues. Minor symptoms (variably advanced bone age and short adult height), if present, are exclusively because of estrogen Excess. Serum estradiol levels are elevated in 48% of affected males, but are not necessarily useful for diagnosis. Molecular analysis of CYP19A1 mutations is mandatory to confirm Aromatase Excess Syndrome diagnosis. Furthermore, the use of an Aromatase inhibitor can ameliorate gynecomastia.
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Aromatase Excess Syndrome a rare autosomal dominant disorder leading to pre or peri pubertal onset gynecomastia
Pediatric endocrinology reviews, 2014Co-Authors: Maki Fukami, Makio Shozu, Keisuke Nagasaki, Mami Miyado, Tsutomu OgataAbstract:Abstract Overexpression of CYP19A1 encoding Aromatase results in a rare genetic disorder referred to as Aromatase Excess Syndrome (AEXS). Male patients with AEXS manifest pre- or peri-pubertal onset gynecomastia, gonadotropin deficiency, and advanced bone age, while female patients are mostly asymptomatic. To date, 30 male patients with molecularly confirmed AEXS have been reported. A total of 12 types of submicroscopic rearrangements, i.e., two simple duplications, four simple deletions, two simple inversions, and four complex rearrangements, have been implicated in AEXS. Clinical severity of AEXS primarily depends on the types of the rearrangements. AEXS appears to account for a small number of cases of pre- or peri-pubertal onset gynecomastia, and should be suspected particularly when gynecomastia is associated with an autosomal dominant inheritance pattern, characteristic hormone abnormalities and/or advanced bone age. Treatment with an Aromatase inhibitor appears to benefit patients with AEXS, although long-term safety of this class of drugs remains unknown.
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Aromatase Excess Syndrome a rare autosomal dominant disorder leading to pre or peri pubertal onset gynecomastia
Pediatric endocrinology reviews, 2014Co-Authors: Maki Fukami, Makio Shozu, Keisuke Nagasaki, Mami Miyado, Tsutomu OgataAbstract:Abstract Overexpression of CYP19A1 encoding Aromatase results in a rare genetic disorder referred to as Aromatase Excess Syndrome (AEXS). Male patients with AEXS manifest pre- or peri-pubertal onset gynecomastia, gonadotropin deficiency, and advanced bone age, while female patients are mostly asymptomatic. To date, 30 male patients with molecularly confirmed AEXS have been reported. A total of 12 types of submicroscopic rearrangements, i.e., two simple duplications, four simple deletions, two simple inversions, and four complex rearrangements, have been implicated in AEXS. Clinical severity of AEXS primarily depends on the types of the rearrangements. AEXS appears to account for a small number of cases of pre- or peri-pubertal onset gynecomastia, and should be suspected particularly when gynecomastia is associated with an autosomal dominant inheritance pattern, characteristic hormone abnormalities and/or advanced bone age. Treatment with an Aromatase inhibitor appears to benefit patients with AEXS, although long-term safety of this class of drugs remains unknown.
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molecular bases and phenotypic determinants of Aromatase Excess Syndrome
International Journal of Endocrinology, 2012Co-Authors: Maki Fukami, Makio Shozu, Tsutomu OgataAbstract:Aromatase Excess Syndrome (AEXS) is a rare autosomal dominant disorder characterized by gynecomastia. This condition is caused by overexpression of CYP19A1 encoding Aromatase, and three types of cryptic genomic rearrangement around CYP19A1, that is, duplications, deletions, and inversions, have been identified in AEXS. Duplications appear to have caused CYP19A1 overexpression because of an increased number of physiological promoters, whereas deletions and inversions would have induced wide CYP19A1 expression due to the formation of chimeric genes consisting of a noncoding exon(s) of a neighboring gene and CYP19A1 coding exons. Genotype-phenotype analysis implies that phenotypic severity of AEXS is primarily determined by the expression pattern of CYP19A1 and the chimeric genes and by the structural property of the fused exons with a promoter function (i.e., the presence or the absence of a natural translation start codon). These results provide novel information about molecular mechanisms of human genetic disorders and biological function of estrogens.
Makio Shozu - One of the best experts on this subject based on the ideXlab platform.
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understanding the pathological manifestations of Aromatase Excess Syndrome lessons for clinical diagnosis
Expert Review of Endocrinology & Metabolism, 2014Co-Authors: Makio Shozu, Maki Fukami, Tsutomu OgataAbstract:Aromatase Excess Syndrome is characterized by pre- or peripubertal onset of gynecomastia due to estrogen Excess because of a gain-of-function mutation in the Aromatase gene (CYP19A1). Subchromosomal recombination events including duplication, deletion, and inversion has been identified. The latter two recombinations recruit novel promoters for CYP19A1 through a unique mechanism. Gynecomastia continues for life, and although the general condition is well preserved, it may cause psychological issues. Minor symptoms (variably advanced bone age and short adult height), if present, are exclusively because of estrogen Excess. Serum estradiol levels are elevated in 48% of affected males, but are not necessarily useful for diagnosis. Molecular analysis of CYP19A1 mutations is mandatory to confirm Aromatase Excess Syndrome diagnosis. Furthermore, the use of an Aromatase inhibitor can ameliorate gynecomastia.
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Aromatase Excess Syndrome a rare autosomal dominant disorder leading to pre or peri pubertal onset gynecomastia
Pediatric endocrinology reviews, 2014Co-Authors: Maki Fukami, Makio Shozu, Keisuke Nagasaki, Mami Miyado, Tsutomu OgataAbstract:Abstract Overexpression of CYP19A1 encoding Aromatase results in a rare genetic disorder referred to as Aromatase Excess Syndrome (AEXS). Male patients with AEXS manifest pre- or peri-pubertal onset gynecomastia, gonadotropin deficiency, and advanced bone age, while female patients are mostly asymptomatic. To date, 30 male patients with molecularly confirmed AEXS have been reported. A total of 12 types of submicroscopic rearrangements, i.e., two simple duplications, four simple deletions, two simple inversions, and four complex rearrangements, have been implicated in AEXS. Clinical severity of AEXS primarily depends on the types of the rearrangements. AEXS appears to account for a small number of cases of pre- or peri-pubertal onset gynecomastia, and should be suspected particularly when gynecomastia is associated with an autosomal dominant inheritance pattern, characteristic hormone abnormalities and/or advanced bone age. Treatment with an Aromatase inhibitor appears to benefit patients with AEXS, although long-term safety of this class of drugs remains unknown.
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Aromatase Excess Syndrome a rare autosomal dominant disorder leading to pre or peri pubertal onset gynecomastia
Pediatric endocrinology reviews, 2014Co-Authors: Maki Fukami, Makio Shozu, Keisuke Nagasaki, Mami Miyado, Tsutomu OgataAbstract:Abstract Overexpression of CYP19A1 encoding Aromatase results in a rare genetic disorder referred to as Aromatase Excess Syndrome (AEXS). Male patients with AEXS manifest pre- or peri-pubertal onset gynecomastia, gonadotropin deficiency, and advanced bone age, while female patients are mostly asymptomatic. To date, 30 male patients with molecularly confirmed AEXS have been reported. A total of 12 types of submicroscopic rearrangements, i.e., two simple duplications, four simple deletions, two simple inversions, and four complex rearrangements, have been implicated in AEXS. Clinical severity of AEXS primarily depends on the types of the rearrangements. AEXS appears to account for a small number of cases of pre- or peri-pubertal onset gynecomastia, and should be suspected particularly when gynecomastia is associated with an autosomal dominant inheritance pattern, characteristic hormone abnormalities and/or advanced bone age. Treatment with an Aromatase inhibitor appears to benefit patients with AEXS, although long-term safety of this class of drugs remains unknown.
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molecular bases and phenotypic determinants of Aromatase Excess Syndrome
International Journal of Endocrinology, 2012Co-Authors: Maki Fukami, Makio Shozu, Tsutomu OgataAbstract:Aromatase Excess Syndrome (AEXS) is a rare autosomal dominant disorder characterized by gynecomastia. This condition is caused by overexpression of CYP19A1 encoding Aromatase, and three types of cryptic genomic rearrangement around CYP19A1, that is, duplications, deletions, and inversions, have been identified in AEXS. Duplications appear to have caused CYP19A1 overexpression because of an increased number of physiological promoters, whereas deletions and inversions would have induced wide CYP19A1 expression due to the formation of chimeric genes consisting of a noncoding exon(s) of a neighboring gene and CYP19A1 coding exons. Genotype-phenotype analysis implies that phenotypic severity of AEXS is primarily determined by the expression pattern of CYP19A1 and the chimeric genes and by the structural property of the fused exons with a promoter function (i.e., the presence or the absence of a natural translation start codon). These results provide novel information about molecular mechanisms of human genetic disorders and biological function of estrogens.
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Aromatase Excess Syndrome identification of cryptic duplications and deletions leading to gain of function of cyp19a1 and assessment of phenotypic determinants
The Journal of Clinical Endocrinology and Metabolism, 2011Co-Authors: Maki Fukami, Makio Shozu, Shun Soneda, Fumiko Kato, Akemi Inagaki, Hiroshi Takagi, Keiichi Hanaki, Susumu Kanzaki, Kenji Ohyama, Tomoaki SanoAbstract:Molecular and clinical studies in 18 males with Aromatase Excess Syndrome clarified novel genetic mechanisms and primary phenotypic determinants of this disorder.
Mami Miyado - One of the best experts on this subject based on the ideXlab platform.
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Aromatase Excess Syndrome a rare autosomal dominant disorder leading to pre or peri pubertal onset gynecomastia
Pediatric endocrinology reviews, 2014Co-Authors: Maki Fukami, Makio Shozu, Keisuke Nagasaki, Mami Miyado, Tsutomu OgataAbstract:Abstract Overexpression of CYP19A1 encoding Aromatase results in a rare genetic disorder referred to as Aromatase Excess Syndrome (AEXS). Male patients with AEXS manifest pre- or peri-pubertal onset gynecomastia, gonadotropin deficiency, and advanced bone age, while female patients are mostly asymptomatic. To date, 30 male patients with molecularly confirmed AEXS have been reported. A total of 12 types of submicroscopic rearrangements, i.e., two simple duplications, four simple deletions, two simple inversions, and four complex rearrangements, have been implicated in AEXS. Clinical severity of AEXS primarily depends on the types of the rearrangements. AEXS appears to account for a small number of cases of pre- or peri-pubertal onset gynecomastia, and should be suspected particularly when gynecomastia is associated with an autosomal dominant inheritance pattern, characteristic hormone abnormalities and/or advanced bone age. Treatment with an Aromatase inhibitor appears to benefit patients with AEXS, although long-term safety of this class of drugs remains unknown.
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Aromatase Excess Syndrome a rare autosomal dominant disorder leading to pre or peri pubertal onset gynecomastia
Pediatric endocrinology reviews, 2014Co-Authors: Maki Fukami, Makio Shozu, Keisuke Nagasaki, Mami Miyado, Tsutomu OgataAbstract:Abstract Overexpression of CYP19A1 encoding Aromatase results in a rare genetic disorder referred to as Aromatase Excess Syndrome (AEXS). Male patients with AEXS manifest pre- or peri-pubertal onset gynecomastia, gonadotropin deficiency, and advanced bone age, while female patients are mostly asymptomatic. To date, 30 male patients with molecularly confirmed AEXS have been reported. A total of 12 types of submicroscopic rearrangements, i.e., two simple duplications, four simple deletions, two simple inversions, and four complex rearrangements, have been implicated in AEXS. Clinical severity of AEXS primarily depends on the types of the rearrangements. AEXS appears to account for a small number of cases of pre- or peri-pubertal onset gynecomastia, and should be suspected particularly when gynecomastia is associated with an autosomal dominant inheritance pattern, characteristic hormone abnormalities and/or advanced bone age. Treatment with an Aromatase inhibitor appears to benefit patients with AEXS, although long-term safety of this class of drugs remains unknown.
Keisuke Nagasaki - One of the best experts on this subject based on the ideXlab platform.
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long term effect of Aromatase inhibition in Aromatase Excess Syndrome
Journal of the Endocrine Society, 2021Co-Authors: Gerhard Binder, Maki Fukami, Tsutomu Ogata, Akie Nakamura, Roland Schweizer, Keisuke NagasakiAbstract:CONTEXT Aromatase Excess Syndrome (AEXS) is a very rare disorder characterized by prepubertal gynecomastia, bone age acceleration, and early growth arrest. Heterozygote submicroscopic rearrangements within the promotor of CYP19A1 result in overexpression of Aromatase and enhanced aromatization of androgens. OBJECTIVE The objective was to study long-term treatment effects of an Aromatase inhibitor. METHODS Data from 7 boys with AEXS were retrospectively collected. Genetic analysis revealed upstream of CYP19A1 a 165 901 bp deletion in 4 German cousins, a 198 662 bp deletion in 2 Japanese brothers, and a 387 622 bp tandem duplication in a Japanese boy. RESULTS All boys developed prepubertal gynecomastia, at median 9.0 years of age (range: 7.0-11.0). Height was +1.20 standard deviation score (SDS) (-0.24 to +1.98); predicted adult height was -1.29 SDS (-3.29 to +1.09). Four boys were treated with 1.0 mg of anastrozole daily, while 3 reached adult height untreated. Treatment with anastrozole was stopped after 5.6 years (4.0-6.8). Three treated boys exceeded their prognosis by 2.4, 6.9, and 8.1 cm, while 1 untreated boy fell below the prognosis by 8.6 cm. One treated with a low dose and 2 untreated reached their prognosis. Adult heights were -0.91 SDS with anastrozole (-2.86 to -0.29) and -0.15 SDS without (-2.31 to -0.03). Distance to target height was -0.22 SDS with anastrozole (-1.72 to +0.52) and +0.54 SDS without (+0.23 to +1.30). CONCLUSION Spontaneous growth in AEXS varied, even in the same family. Our data suggest that early started, long-term inhibition by anastrozole promotes adult height in boys with AEXS.
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Aromatase Excess Syndrome a rare autosomal dominant disorder leading to pre or peri pubertal onset gynecomastia
Pediatric endocrinology reviews, 2014Co-Authors: Maki Fukami, Makio Shozu, Keisuke Nagasaki, Mami Miyado, Tsutomu OgataAbstract:Abstract Overexpression of CYP19A1 encoding Aromatase results in a rare genetic disorder referred to as Aromatase Excess Syndrome (AEXS). Male patients with AEXS manifest pre- or peri-pubertal onset gynecomastia, gonadotropin deficiency, and advanced bone age, while female patients are mostly asymptomatic. To date, 30 male patients with molecularly confirmed AEXS have been reported. A total of 12 types of submicroscopic rearrangements, i.e., two simple duplications, four simple deletions, two simple inversions, and four complex rearrangements, have been implicated in AEXS. Clinical severity of AEXS primarily depends on the types of the rearrangements. AEXS appears to account for a small number of cases of pre- or peri-pubertal onset gynecomastia, and should be suspected particularly when gynecomastia is associated with an autosomal dominant inheritance pattern, characteristic hormone abnormalities and/or advanced bone age. Treatment with an Aromatase inhibitor appears to benefit patients with AEXS, although long-term safety of this class of drugs remains unknown.
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Aromatase Excess Syndrome a rare autosomal dominant disorder leading to pre or peri pubertal onset gynecomastia
Pediatric endocrinology reviews, 2014Co-Authors: Maki Fukami, Makio Shozu, Keisuke Nagasaki, Mami Miyado, Tsutomu OgataAbstract:Abstract Overexpression of CYP19A1 encoding Aromatase results in a rare genetic disorder referred to as Aromatase Excess Syndrome (AEXS). Male patients with AEXS manifest pre- or peri-pubertal onset gynecomastia, gonadotropin deficiency, and advanced bone age, while female patients are mostly asymptomatic. To date, 30 male patients with molecularly confirmed AEXS have been reported. A total of 12 types of submicroscopic rearrangements, i.e., two simple duplications, four simple deletions, two simple inversions, and four complex rearrangements, have been implicated in AEXS. Clinical severity of AEXS primarily depends on the types of the rearrangements. AEXS appears to account for a small number of cases of pre- or peri-pubertal onset gynecomastia, and should be suspected particularly when gynecomastia is associated with an autosomal dominant inheritance pattern, characteristic hormone abnormalities and/or advanced bone age. Treatment with an Aromatase inhibitor appears to benefit patients with AEXS, although long-term safety of this class of drugs remains unknown.