Scalp–ear–nipple syndrome

Scalp–ear–nipple syndrome (SEN syndrome), also known as Finlay–Marks syndrome, is a rare autosomal dominant condition associated with aplasia cutis congenita, characterised by a triad of scalp defects, ear abnormalities and absent or rudimentary nipples头皮-耳-乳腺综合征（SEN 综合征），也称 Finlay-Marks 综合征，是一种与先天性皮肤发育不全相关的罕见常染色体显性遗传病，以头皮缺陷、耳部异常和乳头缺如或发育不全三联征为特征。

The condition has been described in approximately 30 cases, and is caused by mutations in the KCTD1 gene该病已描述约30例，由 KCTD1 基因突变引起。

Other features include dental abnormalities, syndactyly and renal and urinary tract anomalies, and the condition is inherited in an autosomal dominant pattern其他特征包括牙齿异常、并指（趾）畸形以及肾脏和泌尿道异常，该病以常染色体显性模式遗传。

Terminology and classification

• Scalp–ear–nipple syndrome is classified as a rare genetic disorder with ectodermal and renal involvement头皮-耳-乳腺综合征归类为具有外胚层和肾脏受累的罕见遗传病。^[1]
• The condition is also known as Finlay–Marks syndrome, after the authors who first characterised it该病也称为 Finlay-Marks 综合征，以首次描述它的作者命名。^[1]
• MONDO catalogues the condition as MONDO:0008404, Orphanet assigns ORPHA:2036, and OMIM 181270 records the causative locusMONDO 将该病编目为 MONDO:0008404，Orphanet 赋予 ORPHA:2036，OMIM 181270 记录致病位点。
• Cross-references include MeSH C536623, GARD 159 and UMLS C1867020, and the condition is associated with aplasia cutis congenita交叉引用包括 MeSH C536623、GARD 159 和 UMLS C1867020，该病与先天性皮肤发育不全相关。
• The condition is caused by mutations in the KCTD1 gene, establishing the molecular basis of the disorder该病由 KCTD1 基因突变引起，确立了该病的分子基础。
• The syndrome meets the Chinese rare disease criterion of fewer than 140,000 patients nationwide该综合征符合中国罕见病标准（全国患者数少于14万）。^[1]

History

• Scalp–ear–nipple syndrome was first characterised by Finlay and Marks, after whom the syndrome is also named头皮-耳-乳腺综合征由 Finlay 和 Marks 首次描述，该综合征也以他们的名字命名。^[1]
• The triad of scalp defects, ear abnormalities and nipple anomalies was established as the cardinal feature of the condition头皮缺陷、耳部异常和乳头异常三联征被确立为该病的主要特征。^[1]
• Additional features including dental abnormalities and renal anomalies were subsequently described, expanding the clinical spectrum随后描述了包括牙齿异常和肾脏异常在内的额外特征，扩大了临床谱系。^[1]
• The genetic basis was identified when mutations in the KCTD1 gene were found in affected families当在受累家庭中发现 KCTD1 基因突变时确定了遗传基础。
• Approximately 30 cases have been described in the medical literature to date迄今为止，医学文献中已描述约30例。^[1]

Epidemiology

• Scalp–ear–nipple syndrome is rare, with approximately 30 cases described in the medical literature头皮-耳-乳腺综合征罕见，医学文献中描述了约30例。^[1]
• The condition is inherited in an autosomal dominant pattern, with both familial and sporadic cases reported该病以常染色体显性模式遗传，报告了家族性和散发性病例。^[1]
• Both sexes are affected equally, and no specific geographic or ethnic predilection has been reported两性均等受累，未报告特定的地理或民族偏好。^[1]
• Symptoms are present from birth, with the scalp defects being apparent at delivery症状从出生时即存在，头皮缺陷在分娩时即明显。^[1]
• Renal and urinary tract anomalies, when present, may contribute to morbidity and require monitoring当存在时，肾脏和泌尿道异常可能导致发病率并需要监测。^[1]

Pathophysiology

• Scalp–ear–nipple syndrome is caused by heterozygous mutations in the KCTD1 gene, which encodes a transcriptional repressor involved in development头皮-耳-乳腺综合征由 KCTD1 基因的杂合突变引起，该基因编码参与发育的转录抑制因子。
• KCTD1 regulates the transcription of genes involved in ectodermal development, and its dysfunction leads to abnormal development of ectodermal derivativesKCTD1 调节参与外胚层发育的基因转录，其功能障碍导致外胚层衍生物发育异常。
• The scalp defects result from failure of the skin to close properly over the skull, a manifestation of aplasia cutis congenita头皮缺陷源于皮肤未能在颅骨上正确闭合，是先天性皮肤发育不全的表现。^[1]
• The ear abnormalities result from abnormal development of the pinna and associated structures during embryogenesis耳部异常源于胚胎发生期间耳廓和相关结构发育异常。^[1]
• The absent or rudimentary nipples result from failure of the mammary ridges to develop normally during embryogenesis乳头缺如或发育不全源于胚胎发生期间乳腺嵴未能正常发育。^[1]
• The dental abnormalities and syndactyly reflect the broader ectodermal involvement in the condition牙齿异常和并指（趾）反映该病中更广泛的外胚层受累。^[1]

Clinical features

• The cardinal triad comprises scalp defects, ear abnormalities and absent or rudimentary nipples主要三联征包括头皮缺陷、耳部异常和乳头缺如或发育不全。^[1]
• The scalp defects present as raised nodules over the posterior scalp, covered by scarred non-hair-bearing skin头皮缺陷表现为后头皮的隆起结节，覆盖瘢痕化的无毛皮肤。^[1]
• The ear abnormalities include abnormal pinna shape, with the superior edge turned over more than usual, and small tragus, antitragus and lobule耳部异常包括耳廓形状异常，上缘比通常更向内卷曲，以及小的耳屏、对耳屏和耳垂。^[1]
• The nipples are absent or rudimentary, and the breasts may be small or virtually absent乳头缺如或发育不全，乳房可能较小或几乎缺失。^[1]
• Dental abnormalities include missing or widely spaced teeth, and syndactyly involves proximal fusion of digits牙齿异常包括牙齿缺失或间距过大，并指涉及指（趾）近端融合。^[1]
• Complications include renal and urinary tract anomalies, which may require monitoring and management并发症包括肾脏和泌尿道异常，可能需要监测和管理。^[1]

Diagnosis

• Diagnosis is based on the characteristic clinical triad of scalp defects, ear abnormalities and nipple anomalies诊断基于头皮缺陷、耳部异常和乳头异常的特征性临床三联征。^[1]
• Genetic testing for KCTD1 mutations by sequencing confirms the diagnosis in suspected cases通过测序的 KCTD1 突变基因检测确认疑似病例的诊断。
• Renal ultrasound is recommended to assess for renal and urinary tract anomalies建议进行肾超声以评估肾脏和泌尿道异常。^[1]
• The differential diagnosis includes other aplasia cutis congenita syndromes and other ectodermal dysplasia syndromes鉴别诊断包括其他先天性皮肤发育不全综合征和其他外胚层发育不良综合征。^[1]
• Genetic counselling is important for affected families given the autosomal dominant inheritance and 50 per cent transmission risk鉴于常染色体显性遗传和50%的传播风险，遗传咨询对受累家庭很重要。^[1]
• Prenatal diagnosis may be possible through molecular analysis if the familial mutation is known如果已知家族性突变，可通过分子分析进行产前诊断。

Management

• Management is supportive and multidisciplinary, targeting the individual manifestations of the syndrome管理是支持性和多学科的，针对该综合征的个体表现。^[1]
• Management of scalp defects may include conservative wound care or surgical repair, depending on the size头皮缺陷的管理可能包括保守性伤口护理或手术修复，取决于大小。^[1]
• Surgical reconstruction may be considered for ear abnormalities and absent nipples, though this is often for cosmetic purposes可考虑耳部异常和乳头缺如的手术重建，尽管这通常是为了美容目的。^[1]
• Dental management and orthodontic treatment may be required for the dental abnormalities牙齿异常可能需要牙科管理和正畸治疗。^[1]
• Monitoring of renal function is important for patients with renal and urinary tract anomalies肾功能监测对肾脏和泌尿道异常患者很重要。^[1]
• The prognosis is generally good, with normal lifespan, though the condition requires lifelong management of the associated features预后通常良好，寿命正常，尽管该病需要终身管理相关特征。^[1]

Research and controversies

• The genotype-phenotype correlation between specific KCTD1 mutations and the severity of the phenotype is an area of active research特定 KCTD1 突变与表型严重程度之间的基因型-表型相关性是活跃的研究领域。
• The function of KCTD1 in ectodermal development and the mechanism by which mutations cause the syndrome are not fully understoodKCTD1 在外胚层发育中的功能以及突变引起该综合征的机制尚未完全理解。
• The long-term outcomes, particularly regarding renal function and the risk of malignancy, are not well characterized长期结局，特别是关于肾功能和恶性肿瘤风险，尚未充分描述。^[1]
• Several clinical trials are registered on ClinicalTrials.gov for treatments of ectodermal dysplasia syndromesClinicalTrials.gov 上注册了多项外胚层发育不良综合征治疗的临床试验。
• Further research is needed to understand the pathophysiology and develop targeted therapies需要进一步研究以理解病理生理学并开发靶向治疗。

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