Polydactyly-myopia syndrome

Polydactyly-myopia syndrome, also called Czeizel-Brooser syndrome, is an exceedingly rare inherited disorder that combines postaxial polydactyly of all four limbs with progressive myopia多指-近视综合征又称 Czeizel-Brooser 综合征，是一种极罕见的遗传性疾病，以四肢轴后多指合并进行性近视为特征。

It was delineated in 1986 in nine affected members of a four-generation Hungarian family, and only isolated reports have followed since then该病于1986年在一个匈牙利家系的四代共九名患者中被确立，此后仅有零星病例报告。

Care is supportive and surgical, combining ophthalmic surveillance of high myopia with excision of supernumerary digits and repair of associated hernia or cryptorchidism治疗以支持与手术为主，包括对高度近视的眼科监测、多余指切除以及合并疝或隐睾的修补。

Terminology and classification

• The eponym Czeizel-Brooser syndrome honours the Hungarian clinical geneticist Andrew Czeizel and the ophthalmologist G. Brooser, who described the family in 1986Czeizel-Brooser 综合征这一名称纪念匈牙利临床遗传学家安德鲁·切泽尔与眼科医生 G. 布罗泽，他们于1986年描述了该家系。^[1]
• Postaxial polydactyly denotes an extra digit on the ulnar side of the hand or the fibular side of the foot, and in this syndrome both hands and both feet are involved轴后多指指手部尺侧或足部腓侧多出一个指趾，本综合征中双手与双足均受累。^[1]
• It belongs to syndromic polydactyly rather than isolated postaxial polydactyly, because limb duplication coexists with progressive refractive error and with abdominal or genital anomalies该病属于综合征性多指而非孤立性轴后多指，因为肢体重复与进行性屈光不正以及腹部或生殖器异常并存。^[2]
• ICD-10 places it under Q87.2, congenital malformation syndromes predominantly involving limbs, while no dedicated ICD-11 code has been assigned《国际疾病分类》第十版将其归入 Q87.2，即主要累及肢体的先天性畸形综合征，第十一版尚未赋予专门编码。^[1]
• Orphanet lists ORPHA:2917 and OMIM records phenotype 174310, with cross-references to MONDO:0008268, GARD 0004413, MeSH C536331, MedGen 357424, UMLS C1868117 and Wikidata Q55781385Orphanet 将其列为 ORPHA:2917，OMIM 记录表型编号 174310，并交叉参照 MONDO:0008268、GARD 0004413、MeSH C536331、MedGen 357424、UMLS C1868117 与 Wikidata Q55781385。^[1]
• It must be separated from deafness-myopia syndrome caused by SLITRK6, from Stickler and Knobloch syndromes, and from ciliopathies such as Bardet-Biedl syndrome该病需与 SLITRK6 所致的耳聋-近视综合征、Stickler 综合征、Knobloch 综合征以及 Bardet-Biedl 综合征等纤毛病相鉴别。^[3]

History

• In 1986 Czeizel and Brooser reported nine affected people in four generations of a single Hungarian family and proposed autosomal dominant inheritance1986年切泽尔与布罗泽报告了一个匈牙利家系四代中的九名患者，并提出常染色体显性遗传模式。^[1]
• A Hungarian-language paper in the same year described the same family as postaxial polydactyly with progressive myopia of dominant heredity同年一篇匈牙利语论文将同一家系描述为显性遗传的轴后多指合并进行性近视。^[4]
• The original report emphasised duplication of every limb, progressive myopia, bilateral congenital inguinal hernia and undescended testes原始报告强调四肢重复畸形、进行性近视、双侧先天性腹股沟疝与隐睾。^[1]
• For decades after 1986 no further families were published, and Orphanet and MONDO still describe the entity as exceedingly rare with an uncertain prevalence1986年之后的数十年间未见新的家系报告，Orphanet 与 MONDO 至今仍将该实体描述为极罕见且患病率不明。^[1]
• In 2024 a 28-year-old man born to consanguineous parents was reported with severe myopia, high-myopia fundus changes, polydactyly of all limbs and a family history of both traits, which complicated the original dominant interpretation2024年一名父母近亲结婚的28岁男性被报告患有重度近视、高度近视性眼底改变、四肢多指以及这两种性状的家族史，这使最初的显性遗传说解释变得复杂。^[5]

Epidemiology

• Orphanet classifies the syndrome as a very rare disease with a prevalence below 1 per 1,000,000Orphanet 将该综合征归类为极罕见病，患病率低于百万分之一。^[1]
• Only nine affected members of the original family and a single additional patient reported in 2024 are documented, so the worldwide prevalence is unknown文献仅记录了原家系的九名患者与2024年报告的一名新增患者，因此全球患病率仍不清楚。^[1]
• The index family was Hungarian, and no ethnic or geographic predilection can be established from such limited data索引家系为匈牙利人，基于如此有限的数据无法确定种族或地域倾向。^[1]
• Age of onset is neonatal or infantile, because limb duplication is present at birth while myopia progresses during childhood发病年龄为新生儿期或婴儿期，因为肢体重复在出生时即存在，而近视在儿童期逐渐进展。^[1]
• The original pedigree suggested autosomal dominant inheritance, with affected members in every generation and transmission through both sexes原始家系谱提示常染色体显性遗传，每代均有患者且男女均可传递。^[1]
• The 2024 patient was born to consanguineous parents, raising the possibility of autosomal recessive inheritance or of a second, unrelated genetic diagnosis2024年的患者父母为近亲结婚，这提示可能存在常染色体隐性遗传或第二种无关的遗传诊断。^[5]
• Mild or unrecognised cases are probably underreported, because isolated postaxial polydactyly is common and myopia is highly prevalent, and a 2019 overview emphasised the complex heritability of refractive error轻型或未被识别的病例很可能被低估，因为孤立性轴后多指较常见且近视十分普遍，2019年的一篇综述也强调屈光不正具有复杂的遗传性。^[6]

Pathophysiology

• The molecular cause is unknown, and no gene has been mapped to the phenotype recorded as OMIM 174310分子病因尚不明确，OMIM 174310 所记录的表型尚未定位到任何基因。^[1]
• Postaxial polydactyly reflects disturbed anterior-posterior patterning of the limb bud, a process controlled by hedgehog signalling and its GLI transcription factors轴后多指反映肢芽前后轴模式形成紊乱，该过程受刺猬信号通路及其 GLI 转录因子调控。^[2]
• GLI3 variants cause Greig cephalopolysyndactyly syndrome, Pallister-Hall syndrome and non-syndromic postaxial polydactyly, but GLI3 has not been implicated in this syndromeGLI3 变异可导致 Greig 头多指并指综合征、Pallister-Hall 综合征与非综合征性轴后多指，但本综合征尚未发现 GLI3 受累。^[2]
• Progressive myopia results mainly from excessive axial elongation of the globe with thinning and remodelling of the sclera and choroid, and the 2025 International Myopia Institute report links these changes to retinal, extracellular-matrix and neurodevelopmental pathways进行性近视主要源于眼球过度轴性延长以及巩膜与脉络膜变薄重塑，2025年国际近视研究所报告将这些改变与视网膜、细胞外基质及神经发育通路联系起来。^[7]
• Extreme axial length predisposes to myopic maculopathy, retinal detachment, glaucoma and early cataract, which are the main sight-threatening consequences of the ocular phenotype极度眼轴延长易导致近视性黄斑病变、视网膜脱离、青光眼与早发性白内障，这些是眼部表型的主要致盲后果。^[7]
• A single pleiotropic developmental gene, a contiguous deletion or two independent variants could each explain the combination, and ciliary and extracellular-matrix candidate pathways have not been excluded单个多效发育基因、连续缺失或两个独立变异均可解释这种组合，而纤毛与细胞外基质候选通路尚未被排除。^[7]

Clinical features

• The defining limb anomaly is postaxial polydactyly affecting both hands and both feet, typically with a fully formed or rudimentary extra digit具有定义意义的肢体异常是双手与双足均出现轴后多指，多余指趾通常已完全形成或仅为残迹。^[1]
• Myopia progresses from childhood and may reach high myopia with peripapillary atrophy, a myopic conus and other fundus changes, causing reduced unaided vision and asthenopia近视自儿童期进展，可达高度近视并出现视乳头周围萎缩、近视弧及其他眼底改变，造成裸眼视力下降与视疲劳。^[5]
• Bilateral congenital inguinal hernia was part of the original phenotype and may be present at birth or appear in infancy双侧先天性腹股沟疝属于原始表型的一部分，可在出生时存在或在婴儿期出现。^[1]
• Undescended testes, or cryptorchidism, was described in affected males of the original family原家系中的受累男性存在隐睾。^[1]
• Cosmetic and functional problems include difficulty with footwear, pain, tripping and impaired grip when the extra digits are large or malaligned当多余指趾较大或排列不齐时，可出现穿鞋困难、疼痛、易绊倒与抓握功能受损等外观与功能问题。^[2]
• Incarceration of an inguinal hernia and impaired fertility or malignancy risk from untreated cryptorchidism are potential complications腹股沟疝嵌顿以及未治疗隐睾所致生育力受损或恶变风险是潜在并发症。^[1]
• Additional anomalies have not been systematically defined, and the paucity of patients prevents a complete description of the phenotypic spectrum其他异常尚未被系统界定，患者数量稀少也使得无法完整描述表型谱。^[1]

Diagnosis

• Diagnosis is clinical and requires the combination of postaxial polydactyly in all four limbs with progressive myopia, usually in the context of a positive family history诊断基于临床，要求四肢轴后多指与进行性近视同时存在，通常还有阳性家族史。^[1]
• Cycloplegic refraction, axial-length measurement, dilated fundus examination and optical coherence tomography document the severity of myopia and any retinal change睫状肌麻痹验光、眼轴测量、散瞳眼底检查与光学相干断层扫描可记录近视严重程度及任何视网膜改变。^[7]
• Radiographs of the hands and feet define whether the supernumerary digit contains bone and how it articulates with the fifth ray手部与足部X线可确定多余指趾是否含骨以及其与第五射线如何构成关节。^[2]
• Abdominal and genital examination with ultrasonography identifies inguinal hernia and cryptorchidism and guides surgical planning腹部与生殖器检查结合超声可发现腹股沟疝与隐睾并指导手术规划。^[1]
• Exome or genome sequencing is appropriate because no single gene is known, and it can exclude Bardet-Biedl syndrome, GLI3 disorders and other syndromic causes由于尚无已知致病基因，适合进行外显子组或基因组测序，并可排除 Bardet-Biedl 综合征、GLI3 相关疾病及其他综合征性病因。^[3]
• The differential diagnosis includes Bardet-Biedl syndrome, Greig cephalopolysyndactyly, Pallister-Hall syndrome, Stickler syndrome, Knobloch syndrome, deafness-myopia syndrome and isolated postaxial polydactyly, and a 2026 review of Bardet-Biedl syndrome stresses its multiorgan phenotype鉴别诊断包括 Bardet-Biedl 综合征、Greig 头多指并指综合征、Pallister-Hall 综合征、Stickler 综合征、Knobloch 综合征、耳聋-近视综合征与孤立性轴后多指，2026年一篇 Bardet-Biedl 综合征综述强调其多器官表型。^[8]
• Antenatal ultrasound may detect polydactyly, but definitive diagnosis requires postnatal ophthalmic and genetic assessment, and counselling must address the uncertain inheritance产前超声可能发现多指，但确诊仍需出生后的眼科与遗传评估，遗传咨询须说明遗传方式的不确定性。^[5]

Management

• Management is multidisciplinary and involves ophthalmology, plastic or orthopaedic surgery, paediatrics, urology, clinical genetics and rehabilitation管理需要多学科协作，涉及眼科、整形或骨科、儿科、泌尿外科、临床遗传学与康复科。^[2]
• Refractive error is corrected with spectacles or contact lenses, and regular cycloplegic refraction is needed because myopia progresses during growth屈光不正通过眼镜或隐形眼镜矫正，由于近视在生长发育期持续进展，需要定期睫状肌麻痹验光。^[7]
• Myopia-control measures such as low-dose atropine, orthokeratology and increased outdoor time are used in children, although evidence specific to this syndrome is lacking and general myopia data are extrapolated儿童可采用低浓度阿托品、角膜塑形镜与增加户外活动等近视控制措施，但缺乏针对本综合征的证据，只能外推一般近视研究数据。^[7]
• High myopia requires periodic dilated fundus examination for retinal tears, detachment, myopic maculopathy and glaucoma, with prompt referral for new flashes, floaters or visual-field loss高度近视需定期散瞳眼底检查以发现视网膜裂孔、脱离、近视性黄斑病变与青光眼，出现新发闪光感、飞蚊症或视野缺损时应立即转诊。^[7]
• Surgical excision of supernumerary digits is offered for function, shoe fitting and appearance, with reconstruction of the fifth ray when the extra digit is well formed多余指趾的切除手术用于改善功能、穿鞋与外观，当多余指趾发育良好时还需重建第五射线。^[2]
• Inguinal hernia repair is performed in infancy, and orchidopexy is recommended within the first 12 to 18 months for cryptorchidism腹股沟疝在婴儿期修补，隐睾则建议在出生后12至18个月内行睾丸固定术。^[1]
• Genetic counselling should explain the reported autosomal dominant pattern, the possibility of recessive inheritance and the value of sequencing for affected families遗传咨询应说明已报告的常染色体显性模式、隐性遗传的可能性以及受累家系进行测序的价值。^[5]
• Low-vision rehabilitation, psychological support and avoidance of unproven therapies complement surgical and ophthalmic care throughout childhood and adult life低视力康复、心理支持以及避免未经证实的疗法，应贯穿儿童期与成年期的外科和眼科照护。^[7]

Research and controversies

• No causative gene has been identified, and the disorder is represented in OMIM only as a phenotype, so exome and genome studies of additional families are the main research priority尚无致病基因被确认，该病在 OMIM 中仅作为表型记录，因此对更多家系进行外显子组与基因组研究是主要研究方向。^[1]
• Inheritance remains unresolved, because the original pedigree supported autosomal dominance while the 2024 consanguineous case suggests recessive inheritance or a dual diagnosis遗传方式仍未明确，因为原始家系支持常染色体显性遗传，而2024年的近亲病例提示隐性遗传或双重诊断。^[1]
• A 2026 report of coexisting CEP290-related Leber congenital amaurosis and GLI3-related postaxial polydactyly shows how two independent variants can mimic a single syndromic entity2026年一份关于 CEP290 相关 Leber 先天性黑矇与 GLI3 相关轴后多指并存的报告表明，两个独立变异可模拟单一综合征实体。^[3]
• It is still debated whether the syndrome is a distinct pleiotropic entity or the coincidence of common myopia with familial polydactyly, and the absence of a natural-history registry with only about 10 documented patients prevents resolution该综合征究竟是独立的多效实体，还是常见近视与家族性多指的偶然共存，仍有争议，而缺乏自然史登记库且仅有约10名有记录患者，使问题难以解决。^[1]

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