Sanjad–Sakati syndrome

Sanjad–Sakati syndrome, also known as Middle East syndrome or hypoparathyroidism-retardation-dysmorphism syndrome, is a rare autosomal recessive disorder characterised by the triad of hypoparathyroidism, severe growth and intellectual disability, and dysmorphic featuresSanjad–Sakati 综合征，也称中东综合征或甲状旁腺功能减退-智力障碍-畸形综合征，是一种罕见的常染色体隐性遗传病，以甲状旁腺功能减退、严重生长和智力障碍以及畸形特征三联征为特征。

The condition is caused by mutations or deletions in the TBCE gene on chromosome 1, and is seen predominantly in offspring of Middle Eastern origin该病由染色体1上 TBCE 基因的突变或缺失引起，主要见于中东裔后代。

The syndrome was first described in Saudi Arabia but has since been reported in Qatari, Kuwaiti, Omani and other Middle Eastern children该综合征最初在沙特阿拉伯描述，但此后在卡塔尔、科威特、阿曼和其他中东儿童中报告。

Terminology and classification

• Sanjad–Sakati syndrome is classified as a rare multiple congenital anomaly syndrome with endocrine, growth and developmental featuresSanjad–Sakati 综合征归类为具有内分泌、生长和发育特征的罕见多发性先天畸形综合征。^[1]
• The condition is also known as hypoparathyroidism-retardation-dysmorphism syndrome, reflecting the cardinal triad of features该病也称为甲状旁腺功能减退-智力障碍-畸形综合征，反映主要三联征。^[1]
• MONDO catalogues the condition as MONDO:0009426, and Orphanet assigns ORPHA:2323, while the OMIM list does not record a separate entry in the retrieved dataMONDO 将该病编目为 MONDO:0009426，Orphanet 赋予 ORPHA:2323，而检索数据中的 OMIM 列表未记录单独条目。
• The condition is caused by mutations or deletions in the TBCE gene, which encodes tubulin-specific chaperone E该病由 TBCE 基因的突变或缺失引起，该基因编码微管蛋白特异性伴侣 E。
• The condition is classified as an ultra-rare disease, and meets the Chinese rare disease criterion of fewer than 140,000 patients nationwide该病归类为超罕见病，符合中国罕见病标准（全国患者数少于14万）。
• The syndrome is distinguished from other hypoparathyroidism syndromes by the combination of the triad with the characteristic dysmorphic features该综合征通过三联征与特征性畸形特征的组合与其他甲状旁腺功能减退综合征区分。^[1]

History

• Sanjad–Sakati syndrome was first described in Saudi Arabia, where the initial cases were identified in children with the characteristic triadSanjad–Sakati 综合征最初在沙特阿拉伯描述，最初的病例在具有特征性三联征的儿童中被识别。^[1]
• Subsequent reports documented the condition in Qatari, Kuwaiti, Omani and other Middle Eastern populations, establishing its geographic distribution后续报告记录了卡塔尔、科威特、阿曼和其他中东人群中的该病，确立了其地理分布。^[1]
• The condition was linked to mutations or deletions in the TBCE gene, establishing the genetic basis of the disorder该病与 TBCE 基因的突变或缺失联系起来，确立了该病的遗传基础。
• The identification of TBCE mutations provided insight into the role of tubulin folding in parathyroid and skeletal developmentTBCE 突变的鉴定提供了对微管蛋白折叠在甲状旁腺和骨骼发育中作用的见解。
• The syndrome is recognised as a significant cause of congenital hypoparathyroidism in the Arabian Peninsula该综合征被认为是阿拉伯半岛先天性甲状旁腺功能减退的重要原因。^[1]

Epidemiology

• Sanjad–Sakati syndrome is most common in the Arabian Peninsula, particularly in Saudi Arabia, Qatar, Kuwait and OmanSanjad–Sakati 综合征在阿拉伯半岛最常见，特别是在沙特阿拉伯、卡塔尔、科威特和阿曼。^[1]
• The condition is inherited in an autosomal recessive pattern, and its high prevalence in the region is attributed to consanguinity该病以常染色体隐性模式遗传，其在该地区的高患病率归因于近亲结婚。^[1]
• Both sexes are affected equally, and symptoms are present from birth or early infancy两性均等受累，症状从出生或婴儿早期即存在。^[1]
• The condition is associated with significant morbidity from hypocalcaemia and developmental delay, and with reduced life expectancy in severe cases该病与低钙血症和发育迟缓引起的显著发病率相关，严重病例预期寿命缩短。^[1]
• Risk factors include consanguinity and a family history of the condition, consistent with its autosomal recessive inheritance危险因素包括近亲结婚和该病的家族史，与其常染色体隐性遗传一致。^[1]

Pathophysiology

• Sanjad–Sakati syndrome is caused by mutations or deletions in the TBCE gene, which encodes tubulin-specific chaperone ESanjad–Sakati 综合征由 TBCE 基因的突变或缺失引起，该基因编码微管蛋白特异性伴侣 E。
• TBCE is one of four proteins involved in the pathway leading to correctly folded beta-tubulin from folding intermediatesTBCE 是参与从折叠中间体到正确折叠β-微管蛋白通路的四种蛋白质之一。
• Loss of TBCE function impairs beta-tubulin folding, disrupting microtubule function and cell division in affected tissuesTBCE 功能丧失损害β-微管蛋白折叠，破坏受累组织中的微管功能和细胞分裂。
• The parathyroid dysgenesis results from abnormal development of the parathyroid glands, leading to hypoparathyroidism and hypocalcaemia甲状旁腺发育不全源于甲状旁腺发育异常，导致甲状旁腺功能减退和低钙血症。^[1]
• The growth retardation and intellectual disability result from abnormal development of the skeleton and the central nervous system生长迟缓和智力障碍源于骨骼和中枢神经系统发育异常。^[1]
• The dysmorphic features, including microcephaly and facial anomalies, reflect abnormal craniofacial development包括小头畸形和面部异常在内的畸形特征反映颅面发育异常。^[1]

Clinical features

• The cardinal triad comprises hypoparathyroidism with hypocalcaemia and tetany, severe growth and intellectual disability, and dysmorphic features主要三联征包括甲状旁腺功能减退伴低钙血症和手足抽搐、严重生长和智力障碍以及畸形特征。^[1]
• Hypoparathyroidism presents with episodes of hypocalcaemia, hypocalcaemic tetany and hypocalcaemic seizures甲状旁腺功能减退表现为低钙血症发作、低钙性手足抽搐和低钙性癫痫发作。^[1]
• Growth retardation presents with intrauterine growth restriction, microcephaly and short stature生长迟缓表现为宫内生长受限、小头畸形和身材矮小。^[1]
• Dysmorphic features include a characteristic facial appearance with a narrow face, prominent forehead, deep-set eyes and micrognathia畸形特征包括特征性面部外观，伴窄脸、突出前额、深陷眼和小颌畸形。^[1]
• Developmental delay is severe, and affected individuals may have intellectual disability and delayed motor milestones发育迟缓严重，受累个体可能有智力障碍和运动里程碑延迟。^[1]
• Complications include recurrent hypocalcaemic seizures, dental abnormalities and delayed puberty并发症包括反复低钙性癫痫发作、牙齿异常和青春期延迟。^[1]

Diagnosis

• Diagnosis is based on the clinical triad of hypoparathyroidism, growth and intellectual disability, and dysmorphic features诊断基于甲状旁腺功能减退、生长和智力障碍以及畸形特征的临床三联征。^[1]
• Biochemical testing shows hypocalcaemia with low or inappropriately normal parathyroid hormone levels, confirming hypoparathyroidism生化检查显示低钙血症伴低或不适当正常的甲状旁腺激素水平，确认甲状旁腺功能减退。^[1]
• Genetic testing for TBCE mutations or deletions by sequencing or deletion/duplication analysis confirms the diagnosis通过测序或缺失/重复分析的 TBCE 突变或缺失基因检测确认诊断。
• The differential diagnosis includes other causes of congenital hypoparathyroidism, such as DiGeorge syndrome and other genetic hypoparathyroidism syndromes鉴别诊断包括先天性甲状旁腺功能减退的其他原因，如 DiGeorge 综合征和其他遗传性甲状旁腺功能减退综合征。^[1]
• Genetic counselling is important for families given the autosomal recessive inheritance and 25 per cent recurrence risk鉴于常染色体隐性遗传和25%的再发风险，遗传咨询对家庭很重要。^[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 focuses on correcting hypocalcaemia and preventing complications, combined with developmental support管理侧重于纠正低钙血症和预防并发症，并结合发育支持。^[1]
• Calcium and vitamin D supplementation is the primary treatment for hypoparathyroidism, with monitoring of serum calcium levels钙和维生素 D 补充是甲状旁腺功能减退的主要治疗，需监测血清钙水平。^[1]
• Severe hypocalcaemia may require intravenous calcium gluconate, and active vitamin D analogues are used for maintenance严重低钙血症可能需要静脉葡萄糖酸钙，活性维生素 D 类似物用于维持治疗。^[1]
• Seizures are managed with anti-seizure medications and correction of hypocalcaemia癫痫发作通过抗癫痫药物和纠正低钙血症管理。^[1]
• Developmental support and educational interventions are important for managing intellectual disability发育支持和教育干预对于管理智力障碍很重要。^[1]
• The prognosis depends on the severity of hypoparathyroidism and developmental delay, with lifelong management usually required预后取决于甲状旁腺功能减退和发育迟缓的严重程度，通常需要终身管理。^[1]

Research and controversies

• The genotype-phenotype correlation between specific TBCE mutations and the severity of the phenotype is an area of active research特定 TBCE 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 optimal vitamin D analogue and dosing regimen for managing hypoparathyroidism in the syndrome are not well established管理该综合征中甲状旁腺功能减退的最佳维生素 D 类似物和给药方案尚未充分确立。^[1]
• The long-term outcomes of patients with Sanjad–Sakati syndrome, particularly regarding renal and skeletal complications, are not well characterizedSanjad–Sakati 综合征患者的长期结局，特别是关于肾脏和骨骼并发症，尚未充分描述。^[1]
• Several clinical trials are registered on ClinicalTrials.gov for treatments of hypoparathyroidism that may apply to this syndromeClinicalTrials.gov 上注册了多项甲状旁腺功能减退治疗的临床试验，可能适用于该综合征。
• Further research is needed to understand the role of TBCE in development and to develop targeted therapies需要进一步研究以理解 TBCE 在发育中的作用并开发靶向治疗。

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