Saito–Kuba–Tsuruta syndrome

Saito–Kuba–Tsuruta syndrome, also known as fibulo-ulnar hypoplasia-renal anomalies syndrome, is a very rare autosomal recessive genetic disorder characterized by fibulo-ulnar dysplasia with renal anomalies and neonatal respiratory failureSaito–Kuba–Tsuruta 综合征，也称为腓骨尺骨发育不良-肾脏异常综合征，是一种极其罕见的常染色体隐性遗传病，以腓骨尺骨发育不良伴肾脏异常和新生儿呼吸衰竭为特征。

The syndrome was first described in 1989 by Saito and colleagues, who reported affected dizygotic twins born to healthy, unrelated parents该综合征由 Saito 等于1989年首次描述，他们报告了一对由健康无关父母所生的患病异卵双胞胎。

The condition has been described in only two siblings in the medical literature, and is lethal at birth due to respiratory failure医学文献中仅描述了两名同胞，该病因呼吸衰竭在出生时即致命。

Terminology and classification

• Saito–Kuba–Tsuruta syndrome is classified as a rare multiple congenital anomaly syndrome with skeletal and renal involvementSaito–Kuba–Tsuruta 综合征归类为具有骨骼和肾脏受累的罕见多发性先天畸形综合征。^[1]
• The condition is also known as fibulo-ulnar hypoplasia-renal anomalies syndrome, reflecting the cardinal features该病也称为腓骨尺骨发育不良-肾脏异常综合征，反映了主要特征。^[1]
• MONDO catalogues the condition as MONDO:0009233, Orphanet assigns ORPHA:2256, and OMIM 228940 records the causative locusMONDO 将该病编目为 MONDO:0009233，Orphanet 赋予 ORPHA:2256，OMIM 228940 记录致病位点。
• Cross-references include MeSH C537226 and UMLS C1856727, and the condition is classified as an ultra-rare disease交叉引用包括 MeSH C537226 和 UMLS C1856727，该病归类为超罕见病。
• The condition is distinguished from other limb-renal syndromes by the specific combination of fibulo-ulnar dysplasia and renal anomalies该病通过腓骨尺骨发育不良和肾脏异常的特定组合与其他肢体-肾脏综合征区分。^[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

• Saito–Kuba–Tsuruta syndrome was first described in April 1989, when Saito and colleagues reported affected dizygotic twinsSaito–Kuba–Tsuruta 综合征于1989年4月首次描述，当时 Saito 等报告了患病的异卵双胞胎。^[1]
• The twins, one male and one female, were born to healthy, young, unrelated parents and presented with the characteristic features这对双胞胎一男一女，由健康、年轻、无血缘关系的父母所生，表现出特征性特征。^[1]
• Autopsy of the male infant revealed truncus arteriosus and ventricular septal defect, and ultrasound had shown one of two gestational sacs deteriorating during pregnancy男婴尸检发现动脉干和室间隔缺损，超声显示妊娠期间两个孕囊之一恶化。^[1]
• The investigation by Saito and colleagues found no other syndrome with the same combination of features, establishing it as a distinct entitySaito 等的调查发现没有其他综合征具有相同的特征组合，将其确立为独立实体。^[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

• Saito–Kuba–Tsuruta syndrome is extremely rare, with only two siblings reported in the medical literatureSaito–Kuba–Tsuruta 综合征极其罕见，医学文献中仅报告了两名同胞。^[1]
• The condition is inherited in an autosomal recessive pattern, based on its occurrence in siblings born to unaffected parents该病以常染色体隐性模式遗传，基于其在未受累父母所生同胞中的发生。^[1]
• Symptoms are present at birth, with skeletal and renal anomalies being apparent in the neonatal period症状在出生时即存在，骨骼和肾脏异常在新生儿期即明显。^[1]
• Both sexes may be affected, as shown by the affected male and female twins in the original report两性均可受累，如原始报告中患病的男女双胞胎所示。^[1]
• The condition is lethal at birth due to neonatal respiratory failure, and the two reported affected siblings both died shortly after birth该病因新生儿呼吸衰竭在出生时致命，报告的两名患病同胞均在出生后不久死亡。^[1]

Pathophysiology

• The genetic cause of Saito–Kuba–Tsuruta syndrome has not been identified, and the condition is presumed to result from a defect in early skeletal and renal developmentSaito–Kuba–Tsuruta 综合征的遗传原因尚未确定，该病被推定源于早期骨骼和肾脏发育缺陷。^[1]
• The fibulo-ulnar dysplasia results from abnormal development of the limb bud during embryogenesis, affecting the fibula and ulna腓骨尺骨发育不良源于胚胎发生期间肢芽发育异常，影响腓骨和尺骨。^[1]
• The renal anomalies, including renal hypoplasia, result from abnormal development of the metanephros during embryogenesis包括肾发育不全在内的肾脏异常源于胚胎发生期间后肾发育异常。^[1]
• The cardiac defects, including truncus arteriosus and ventricular septal defect, reflect abnormal development of the heart during embryogenesis包括动脉干和室间隔缺损在内的心脏缺陷反映胚胎发生期间心脏发育异常。^[1]
• The neonatal respiratory failure results from pulmonary hypoplasia and the associated skeletal and cardiac anomalies新生儿呼吸衰竭源于肺发育不全以及相关的骨骼和心脏异常。^[1]
• The combination of anomalies in different organ systems suggests a defect in a gene involved in early embryonic development不同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 fibulo-ulnar dysplasia with renal anomalies, presenting with neonatal respiratory failure soon after birth主要特征是腓骨尺骨发育不良伴肾脏异常，表现为出生后不久的新生儿呼吸衰竭。^[1]
• Skeletal features include symmetric long bone deficiency, fibular aplasia and symphalangism骨骼特征包括对称性长骨缺陷、腓骨发育不全和并指（趾）畸形。^[1]
• Facial and ear anomalies, including facial dysmorphism and ear abnormalities, are additional features面部和耳部异常，包括面部畸形和耳部异常，是额外特征。^[1]
• Renal anomalies include hypoplasia of the kidney, which contributes to the overall severity of the condition肾脏异常包括肾发育不全，这加剧了该病的整体严重程度。^[1]
• Congenital heart defects, including truncus arteriosus and ventricular septal defect, are present in some affected individuals包括动脉干和室间隔缺损在内的先天性心脏缺陷存在于部分受累个体中。^[1]
• Complications include neonatal death due to respiratory failure, which occurred in both reported cases并发症包括呼吸衰竭引起的新生儿死亡，两例报告病例均发生。^[1]

Diagnosis

• Diagnosis is based on the characteristic combination of fibulo-ulnar dysplasia, renal anomalies and neonatal respiratory failure诊断基于腓骨尺骨发育不良、肾脏异常和新生儿呼吸衰竭的特征性组合。^[1]
• Skeletal radiography identifies the fibulo-ulnar dysplasia and other skeletal abnormalities骨骼 X 线识别腓骨尺骨发育不良和其他骨骼异常。^[1]
• Renal ultrasound identifies the renal anomalies, and echocardiography assesses for cardiac defects肾超声识别肾脏异常，超声心动图评估心脏缺陷。^[1]
• The differential diagnosis includes other limb-renal syndromes such as acro-renal syndromes and other short limb syndromes鉴别诊断包括其他肢体-肾脏综合征，如肢端-肾脏综合征和其他短肢综合征。^[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 and 25 per cent recurrence risk鉴于推定的常染色体隐性遗传和25%的再发风险，建议对受累家庭进行遗传咨询。^[1]

Management

• Management is primarily supportive, as the condition is lethal at birth due to respiratory failure管理主要是支持性的，因为该病因呼吸衰竭在出生时致命。^[1]
• In the few cases where survival occurs, surgical correction of skeletal anomalies may be considered在少数存活病例中，可考虑骨骼异常的手术矫正。^[1]
• Cardiac defects may require surgical repair if the infant survives the neonatal period如果婴儿存活新生儿期，心脏缺陷可能需要手术修复。^[1]
• Renal support, including dialysis, may be required for patients with significant renal hypoplasia对有明显肾发育不全的患者可能需要包括透析在内的肾脏支持。^[1]
• Neonatal intensive care support is essential for managing the respiratory failure at birth新生儿重症监护支持对于管理出生时的呼吸衰竭至关重要。^[1]
• The prognosis is poor, with neonatal death due to respiratory failure being the usual outcome预后差，因呼吸衰竭导致的新生儿死亡是通常的结局。^[1]

Research and controversies

• The genetic cause of Saito–Kuba–Tsuruta syndrome has not been identified, and the condition remains a clinical diagnosisSaito–Kuba–Tsuruta 综合征的遗传原因尚未确定，该病仍是临床诊断。^[1]
• Given the lethality of the condition, research is limited, and most knowledge comes from the original case report鉴于该病的致命性，研究有限，大部分知识来自原始病例报告。^[1]
• Whether the syndrome represents a distinct entity or a variant of another limb-renal syndrome is an area of discussion该综合征是独立实体还是另一肢体-肾脏综合征的变异型是讨论领域。^[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 identify potential therapeutic targets需要进一步研究以理解病理生理学并确定潜在治疗靶点。^[1]

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