Pierson综合征的研究进展

doi:10.12280/gjszjk.20220193

摘要/Abstract

摘要：

Pierson综合征是编码层黏连蛋白β2的基因LAMB2（laminin beta 2）突变导致的常染色体隐性遗传性病,以先天性肾病综合征、早发性肾功能衰竭和双侧小角膜为典型特征。常伴有弥漫性系膜硬化、其他眼部异常以及神经系统异常,发病后通常会迅速发展至肾衰竭。Pierson综合征临床上较为少见,难以依据临床表型进行诊断,容易漏诊和误诊,需要与其他可以引起肾脏异常伴或不伴肾外异常的疾病相鉴别。目前Pierson综合征尚无特定疗法,治疗方法主要是针对性的支持治疗,但预后较差。综述该综合征的研究进展,提高临床医生对Pierson综合征的认识。

关键词: 肾病综合征, 眼疾病, 遗传性疾病,先天性, 层粘连蛋白, 表型, 基因, 突变

Abstract:

Pierson syndrome is an autosomal recessive genetic disease caused by the mutations of LAMB2 gene encoding laminin β2, which is characterized by congenital nephrotic syndrome, early-onset renal failure and bilateral small cornea. It is often accompanied by diffuse mesangial sclerosis, serious other ocular abnormalities and nervous system abnormalities, and often rapidly progresses to renal failure. Pierson syndrome is rare in clinic, which is difficult to diagnose according to clinical phenotype, and is easy to be missed and misdiagnosed. It needs to be differentiated from other disorders that can cause renal abnormalities with or without extrarenal abnormalities. At present, there is no specific therapy for Pierson syndrome, and the treatment methods are mainly targeted in the supportive care. The prognosis of Pierson syndrome is poor. We review the research progress of Pierson syndrome to improve clinicians′ understanding.

Key words: Nephrotic syndrome, Eye diseases, Genetic diseases, inborn, Laminin, Phenotype, Genes, Mutation

廖珍华, 杨峰勋, 蒋洪昆, 卢宇. Pierson综合征的研究进展[J]. 国际生殖健康/计划生育, 2022, 41(4): 332-336.

LIAO Zhen-hua, YANG Feng-xun, JIANG Hong-kun, LU Yu. Advance of Pierson Syndrome[J]. Journal of International Reproductive Health/Family Planning, 2022, 41(4): 332-336.

图/表 2

参考文献 33

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结构域突变体	临床表型
G699R^[20]	婴儿期出现肾脏症状,如低白蛋白血症、蛋白尿、水肿,2岁后迅速发展为终末期肾病综合征,无眼部异常
D167Y^[21]	终末期肾病,视网膜脱离,严重视觉障碍
S179F^[22]	终末期肾病,局灶性和节段性肾小球硬化,视网膜脱离,严重视觉障碍
R246W、R246Q^[13,18]	终末期肾病,肾病蛋白尿,弥漫性系膜硬化,局灶性和节段性肾小球硬化,小角膜,晶状体异常,眼球震颤,肌张力减退,认知缺陷,延迟性肌肉酸痛
L139P^[19]	弥漫性系膜硬化,晶状体异常,严重视觉障碍,肌张力减退,肌肉萎缩,认知障碍
H147R^[23]	肾病蛋白尿,弥漫性系膜硬化,增生性肾小球肾炎,高血压,心力衰竭,小角膜,视网膜脱离,晶状体异常
S80R^[24]	肾病蛋白尿,高水平蛋白尿,轻度弥漫性系膜硬化和肾小管萎缩,近视,视网膜脱离
R964*^[3]	严重肾病蛋白尿伴急性肾功能衰竭,双侧小角膜,视网膜异常,严重肌张力减退,呼吸窘迫
Q1513*^[25]	终末期肾病,肾小管病变,神经源性膀胱,严重神经发育迟缓,癫痫,继发性甲状腺功能减退,小角膜,白内障,眼球震颤

结构域突变体	临床表型
G699R^[20]	婴儿期出现肾脏症状,如低白蛋白血症、蛋白尿、水肿,2岁后迅速发展为终末期肾病综合征,无眼部异常
D167Y^[21]	终末期肾病,视网膜脱离,严重视觉障碍
S179F^[22]	终末期肾病,局灶性和节段性肾小球硬化,视网膜脱离,严重视觉障碍
R246W、R246Q^[13,18]	终末期肾病,肾病蛋白尿,弥漫性系膜硬化,局灶性和节段性肾小球硬化,小角膜,晶状体异常,眼球震颤,肌张力减退,认知缺陷,延迟性肌肉酸痛
L139P^[19]	弥漫性系膜硬化,晶状体异常,严重视觉障碍,肌张力减退,肌肉萎缩,认知障碍
H147R^[23]	肾病蛋白尿,弥漫性系膜硬化,增生性肾小球肾炎,高血压,心力衰竭,小角膜,视网膜脱离,晶状体异常
S80R^[24]	肾病蛋白尿,高水平蛋白尿,轻度弥漫性系膜硬化和肾小管萎缩,近视,视网膜脱离
R964*^[3]	严重肾病蛋白尿伴急性肾功能衰竭,双侧小角膜,视网膜异常,严重肌张力减退,呼吸窘迫
Q1513*^[25]	终末期肾病,肾小管病变,神经源性膀胱,严重神经发育迟缓,癫痫,继发性甲状腺功能减退,小角膜,白内障,眼球震颤

疾病名称	致病基因	遗传类型	临床表现及肾活检结果
Denys-Drash综合征	WT1（常见第8或第9外显子突变）	常染色体显性遗传	通常在2岁前表现为肾病综合征,90%有患肾母细胞瘤和性腺母细胞瘤的风险,性腺发育不全的男性通常不育。女性患者一般具有正常的生殖器官,通常仅诊断为肾病综合征。肾活检显示弥漫性系膜硬化,电镜下可见胶质母细胞不规则增厚
Frasier综合征	WT1（第9内含子突变）	常染色体显性遗传	通常在2~6岁时表现为肾病综合征,多数在青少年时期发展至终末期肾病,与假两性畸形伴外生殖器条纹或带状性腺有关。核型为46, XY的患儿性分化障碍,多数表现为完全的性逆转伴性腺发育不全,其肾病通常是激素抵抗的,需要进行透析或者肾移植。肾活检显示局灶节段性肾小球硬化和胶质母细胞不规则增厚伴足突消失
Galloway-Mowat综合征	LAGE3、OSGEP、 TP53RK、TPRKB、 GON7、YRDC、NUP133、WDR4、GAMOS3等	常染色体隐性遗传	出生后的第1个月内常表现为激素抵抗性肾病综合征和食管裂孔疝,以先天性小头畸形与癫痫发作、超过50%患者伴肌张力减退和发育迟缓为特征,可出现尿血、尿糖和肾功能衰竭。肾活检可显示弥漫性系膜硬化,系膜区分界不清。电镜显示GBM不规则,内、外薄层扩张,足突消失
先天性肾病综合征	NPHS1、NPHS2	常染色体隐性遗传	主要临床特点为重度蛋白尿,伴低白蛋白血症、高脂血症和水肿。部分患者表现为遗传性激素抵抗,最终导致终末期肾衰竭。肾活检显示非特异性肾小球改变,局灶性肾小球硬化和弥漫性系膜硬化,小管囊性扩张
Alport综合征	COL4A3、COL4A4、COL4A5	X连锁遗传（80%）、常染色体显/隐性遗传（15%）	GBM相关的遗传性疾病,是编码Ⅳ型胶原基因突变所致,患者多在10岁前发病,血尿为首发表现,间断或持续性镜下血尿,蛋白尿在病程中较晚出现,肾功能呈慢性进行性减退,可发展为终末期肾病。肾活检显示GBM极不规则、弥漫性增厚或增厚与变薄相间,致密层撕裂分层、篮网状改变是诊断该病的金标准（约60%患者可见）

疾病名称	致病基因	遗传类型	临床表现及肾活检结果
Denys-Drash综合征	WT1（常见第8或第9外显子突变）	常染色体显性遗传	通常在2岁前表现为肾病综合征,90%有患肾母细胞瘤和性腺母细胞瘤的风险,性腺发育不全的男性通常不育。女性患者一般具有正常的生殖器官,通常仅诊断为肾病综合征。肾活检显示弥漫性系膜硬化,电镜下可见胶质母细胞不规则增厚
Frasier综合征	WT1（第9内含子突变）	常染色体显性遗传	通常在2~6岁时表现为肾病综合征,多数在青少年时期发展至终末期肾病,与假两性畸形伴外生殖器条纹或带状性腺有关。核型为46, XY的患儿性分化障碍,多数表现为完全的性逆转伴性腺发育不全,其肾病通常是激素抵抗的,需要进行透析或者肾移植。肾活检显示局灶节段性肾小球硬化和胶质母细胞不规则增厚伴足突消失
Galloway-Mowat综合征	LAGE3、OSGEP、 TP53RK、TPRKB、 GON7、YRDC、NUP133、WDR4、GAMOS3等	常染色体隐性遗传	出生后的第1个月内常表现为激素抵抗性肾病综合征和食管裂孔疝,以先天性小头畸形与癫痫发作、超过50%患者伴肌张力减退和发育迟缓为特征,可出现尿血、尿糖和肾功能衰竭。肾活检可显示弥漫性系膜硬化,系膜区分界不清。电镜显示GBM不规则,内、外薄层扩张,足突消失
先天性肾病综合征	NPHS1、NPHS2	常染色体隐性遗传	主要临床特点为重度蛋白尿,伴低白蛋白血症、高脂血症和水肿。部分患者表现为遗传性激素抵抗,最终导致终末期肾衰竭。肾活检显示非特异性肾小球改变,局灶性肾小球硬化和弥漫性系膜硬化,小管囊性扩张
Alport综合征	COL4A3、COL4A4、COL4A5	X连锁遗传（80%）、常染色体显/隐性遗传（15%）	GBM相关的遗传性疾病,是编码Ⅳ型胶原基因突变所致,患者多在10岁前发病,血尿为首发表现,间断或持续性镜下血尿,蛋白尿在病程中较晚出现,肾功能呈慢性进行性减退,可发展为终末期肾病。肾活检显示GBM极不规则、弥漫性增厚或增厚与变薄相间,致密层撕裂分层、篮网状改变是诊断该病的金标准（约60%患者可见）