Santos–Mateus–Leal syndrome

Santos–Mateus–Leal syndrome, also known as Hirschsprung's disease-deafness-polydactyly syndrome, is a very rare autosomal recessive disorder characterised by Hirschsprung's disease, hand and foot polydactyly, unilateral renal agenesis and congenital hearing lossSantos–Mateus–Leal 综合征，也称为先天性巨结肠-耳聋-多指综合征，是一种极其罕见的常染色体隐性遗传病，以先天性巨结肠、手足多指、单侧肾缺如和先天性听力损失为特征。

Only two cases have been described in medical literature, in two siblings of opposite sex born to consanguineous first-cousin parents医学文献中仅描述了两例，为一对近亲（一级表亲）父母所生的性别相反的同胞。

The syndrome was recognised as a novel entity distinct from previous reports of Hirschsprung's disease with polydactyly and ventricular septal defect该综合征被认定为独立于先前先天性巨结肠伴多指和室间隔缺损报告的独立实体。

Terminology and classification

• Santos–Mateus–Leal syndrome is classified as a rare malformative association with gastrointestinal, limb, renal and auditory involvementSantos–Mateus–Leal 综合征归类为具有胃肠道、肢体、肾脏和听觉受累的罕见畸形关联。^[1]
• The condition is also known as Hirschsprung's disease-deafness-polydactyly syndrome, reflecting the cardinal features该病也称为先天性巨结肠-耳聋-多指综合征，反映了主要特征。^[1]
• MONDO catalogues the condition as MONDO:0009342, Orphanet assigns ORPHA:2155, and OMIM 235740 records the causative locusMONDO 将该病编目为 MONDO:0009342，Orphanet 赋予 ORPHA:2155，OMIM 235740 记录致病位点。
• Cross-references include GARD 157 and UMLS C1856112, and the condition is classified as an ultra-rare disorder交叉引用包括 GARD 157 和 UMLS C1856112，该病归类为超罕见病。
• The condition is distinguished from other Hirschsprung disease associations by the specific combination of deafness and polydactyly该病通过耳聋和多指的特定组合与其他先天性巨结肠关联区分。^[1]
• 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

• Santos–Mateus–Leal syndrome was first described by Santos and colleagues, who reported two affected siblings of opposite sexSantos–Mateus–Leal 综合征由 Santos 等首次描述，他们报告了两名性别相反的患病同胞。^[1]
• The siblings were born to consanguineous first-cousin parents and presented with Hirschsprung's disease, polydactyly, unilateral renal agenesis and congenital hearing loss这对同胞由近亲（一级表亲）父母所生，表现为先天性巨结肠、多指、单侧肾缺如和先天性听力损失。^[1]
• Santos and colleagues concluded that the case represented a novel syndrome distinct from previous reports of Hirschsprung's disease with polydactyly and ventricular septal defectSantos 等得出结论，该病例代表一种独立于先前先天性巨结肠伴多指和室间隔缺损报告的新的综合征。^[1]
• The autosomal recessive inheritance pattern was inferred from the occurrence in siblings born to consanguineous, unaffected parents常染色体隐性遗传模式从近亲、未受累父母所生的同胞中的发生推断。^[1]
• The syndrome was subsequently included in rare disease databases and classified by MONDO and Orphanet该综合征随后被纳入罕见病数据库，并由 MONDO 和 Orphanet 分类。

Epidemiology

• Santos–Mateus–Leal syndrome is extremely rare, with only two cases described in the medical literatureSantos–Mateus–Leal 综合征极其罕见，医学文献中仅描述了两例。^[1]
• The condition is inherited in an autosomal recessive pattern, and its occurrence in consanguineous families is consistent with this该病以常染色体隐性模式遗传，其在近亲家庭中的发生与此一致。^[1]
• Symptoms are present from birth, with Hirschsprung's disease and polydactyly being apparent in the neonatal period症状从出生时即存在，先天性巨结肠和多指在新生儿期即明显。^[1]
• Both sexes may be affected, as shown by the affected siblings of opposite sex in the original report两性均可受累，如原始报告中性别相反的患病同胞所示。^[1]
• No specific geographic or ethnic predilection beyond consanguinity has been reported除近亲结婚外，未报告特定的地理或民族偏好。^[1]

Pathophysiology

• The genetic cause of Santos–Mateus–Leal syndrome has not been identified, and the condition is presumed to result from a defect in early embryonic developmentSantos–Mateus–Leal 综合征的遗传原因尚未确定，该病被推定源于早期胚胎发育缺陷。^[1]
• Hirschsprung's disease results from the absence of ganglion cells in the distal colon, leading to intestinal obstruction先天性巨结肠源于远端结肠中神经节细胞的缺失，导致肠梗阻。^[1]
• The polydactyly results from abnormal limb bud development during embryogenesis, leading to extra digits多指源于胚胎发生期间肢芽发育异常，导致额外指（趾）。^[1]
• The unilateral renal agenesis results from failure of one kidney to develop during embryogenesis单侧肾缺如源于胚胎发生期间一侧肾脏未能发育。^[1]
• The congenital hearing loss results from abnormal development of the inner ear or auditory nerve先天性听力损失源于内耳或听神经发育异常。^[1]
• The combination of anomalies in multiple organ systems suggests a defect in a gene involved in early embryonic development多器官系统中异常的组合提示涉及早期胚胎发育的基因缺陷。^[1]

Clinical features

• The cardinal features are Hirschsprung's disease, hand and foot polydactyly, unilateral renal agenesis and congenital hearing loss主要特征是先天性巨结肠、手足多指、单侧肾缺如和先天性听力损失。^[1]
• Hirschsprung's disease presents with delayed passage of meconium, abdominal distension and vomiting in the neonatal period先天性巨结肠表现为新生儿期胎粪排出延迟、腹胀和呕吐。^[1]
• Polydactyly involves both hands and feet, with supernumerary digits that may be fully formed or rudimentary多指涉及双手和双足，有多余指（趾），可能完全形成或发育不全。^[1]
• Unilateral renal agenesis is usually asymptomatic if the other kidney functions normally, but increases long-term renal risk如果另一侧肾脏功能正常，单侧肾缺如通常无症状，但增加长期肾脏风险。^[1]
• Congenital hearing loss may be sensorineural or conductive and requires audiological assessment先天性听力损失可能是感音神经性或传导性，需要听力学评估。^[1]
• Complications include intestinal obstruction, renal insufficiency in later life and the sequelae of untreated hearing loss并发症包括肠梗阻、晚年肾功能不全和未治疗听力损失的后遗症。^[1]

Diagnosis

• Diagnosis is based on the characteristic combination of Hirschsprung's disease, polydactyly, unilateral renal agenesis and congenital hearing loss诊断基于先天性巨结肠、多指、单侧肾缺如和先天性听力损失的特征性组合。^[1]
• Rectal biopsy confirms Hirschsprung's disease by demonstrating the absence of ganglion cells直肠活检通过证明神经节细胞缺失确认先天性巨结肠。^[1]
• Renal ultrasound identifies unilateral renal agenesis, and audiological assessment confirms the hearing loss肾超声识别单侧肾缺如，听力学评估确认听力损失。^[1]
• The differential diagnosis includes other Hirschsprung disease associations and other polydactyly syndromes鉴别诊断包括其他先天性巨结肠关联和其他多指综合征。^[1]
• Genetic testing is not currently available because the causative gene has not been identified由于致病基因尚未确定，目前无法进行基因检测。^[1]
• Genetic counselling is recommended for affected families given the presumed autosomal recessive inheritance鉴于推定的常染色体隐性遗传，建议对受累家庭进行遗传咨询。^[1]

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]
• Surgical resection of the aganglionic segment is required for Hirschsprung's disease先天性巨结肠需要手术切除无神经节细胞段。^[1]
• Polydactyly may be managed surgically to improve function and appearance多指可通过手术管理以改善功能和外观。^[1]
• Hearing aids or cochlear implants may be required for congenital hearing loss, with early intervention to support development先天性听力损失可能需要助听器或人工耳蜗，并早期干预以支持发育。^[1]
• Monitoring of renal function is important for patients with unilateral renal agenesis肾功能监测对单侧肾缺如患者很重要。^[1]
• The prognosis is generally good with appropriate management, given that the reported cases had a good outcome鉴于报告病例结局良好，经适当管理预后通常良好。^[1]

Research and controversies

• The genetic cause of Santos–Mateus–Leal syndrome has not been identified, and the condition remains a clinical diagnosisSantos–Mateus–Leal 综合征的遗传原因尚未确定，该病仍是临床诊断。^[1]
• Whether the syndrome represents a distinct entity or a variant of another Hirschsprung disease association is an area of discussion该综合征是独立实体还是另一先天性巨结肠关联的变异型是讨论领域。^[1]
• Given the rarity of the condition, the long-term outcomes and quality of life are not well characterized鉴于该病的罕见性，长期结局和生活质量尚未充分描述。^[1]
• The identification of the causative gene would improve diagnosis and enable prenatal testing致病基因的鉴定将改善诊断并使产前检测成为可能。^[1]
• Further research is needed to understand the pathophysiology and to 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。^[1]

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