Saal Bulas syndrome

Saal Bulas syndrome is a very rare genetic disorder characterised by ectrodactyly (lobster-claw hands), diaphragmatic hernia and absence of the corpus callosumSaal Bulas 综合征是一种极其罕见的遗传病，以并指畸形（龙虾样手）、膈疝和胼胝体缺失为特征。

The syndrome was first described in 1995 by the American paediatricians Howard M. Saal and Dorothy I. Bulas, after whom it is named该综合征由美国儿科医生 Howard M. Saal 和 Dorothy I. Bulas 于1995年首次描述，并以他们的名字命名。

It is listed as a rare disease by the Office of Rare Diseases of the National Institutes of Health, affecting fewer than 200,000 people in the United States它被美国国立卫生研究院罕见病办公室列为罕见病，在美国影响少于20万人。

Terminology and classification

• Saal Bulas syndrome is classified as a rare multiple congenital anomaly syndrome with limb, diaphragmatic and central nervous system involvementSaal Bulas 综合征归类为具有肢体、膈肌和中枢神经系统受累的罕见多发性先天畸形综合征。^[1]
• MONDO catalogues the condition as MONDO:0042956 (Saal-Bulas syndrome), and the syndrome is listed in the NIH Rare Diseases databaseMONDO 将该病编目为 MONDO:0042956（Saal-Bulas 综合征），该综合征被列入 NIH 罕见病数据库。
• Cross-references include MeSH C537193, GARD 311 and UMLS C2931439, enabling retrieval across registries交叉引用包括 MeSH C537193、GARD 311 和 UMLS C2931439，使该病可跨登记库检索。
• The condition is classified as an ultra-rare disease, and the inherited pattern has been suggested to be autosomal recessive该病归类为超罕见病，遗传模式被认为可能是常染色体隐性。^[1]
• Saal Bulas syndrome is distinguished from other ectrodactyly syndromes by the combination of lobster-claw hands, diaphragmatic hernia and agenesis of the corpus callosumSaal Bulas 综合征通过龙虾样手、膈疝和胼胝体发育不全的组合与其他并指畸形综合征区分。^[1]
• The condition meets the Chinese rare disease criterion of fewer than 140,000 patients nationwide该病符合中国罕见病标准（全国患者数少于14万）。^[1]

History

• Saal Bulas syndrome was first described in 1995 by Saal and Bulas, who reported the characteristic combination of anomalies in affected patientsSaal Bulas 综合征于1995年由 Saal 和 Bulas 首次描述，他们报告了受累患者的特征性异常组合。^[1]
• The eponym Saal Bulas syndrome was adopted to honour the two paediatricians who first characterised the conditionSaal Bulas 综合征这一命名被采用，以纪念首次描述该病的两位儿科医生。^[1]
• The condition was subsequently included in rare disease databases, though the underlying genetic cause has not yet been identified该病随后被纳入罕见病数据库，尽管潜在遗传原因尚未确定。^[1]
• Further case reports have expanded the recognised clinical spectrum, with additional features such as cardiac septal defects being described进一步的病例报告扩大了已知临床谱系，描述了如心脏间隔缺损等额外特征。^[1]
• Research into the genetic basis of the syndrome is ongoing, with candidate genes under investigation对该综合征遗传基础的研究正在进行中，候选基因正在研究中。

Epidemiology

• Saal Bulas syndrome is extremely rare, with only a small number of cases reported in the medical literatureSaal Bulas 综合征极其罕见，医学文献中仅报告了少量病例。^[1]
• The condition is listed as a rare disease by the NIH Office of Rare Diseases, meaning it affects fewer than 200,000 people in the United States该病被 NIH 罕见病办公室列为罕见病，意味着它在美国影响少于20万人。^[1]
• Symptoms are present from birth, with the limb and diaphragmatic anomalies being apparent at delivery症状从出生时即存在，肢体和膈肌异常在分娩时即明显。^[1]
• Both sexes may be affected, and the condition has been reported in consanguineous families两性均可受累，该病已在近亲家庭中报告。^[1]
• Complications including respiratory distress and neonatal death contribute to the significant mortality associated with the syndrome包括呼吸窘迫和新生儿死亡在内的并发症导致与该综合征相关的显著死亡率。^[1]

Pathophysiology

• The exact genetic cause of Saal Bulas syndrome has not been identified, and the condition is presumed to have a genetic basis given its familial occurrenceSaal Bulas 综合征的确切遗传原因尚未确定，鉴于其家族性发生，该病被推定具有遗传基础。^[1]
• The ectrodactyly results from abnormal development of the limb bud during embryogenesis, leading to the characteristic lobster-claw deformity并指畸形源于胚胎发生期间肢芽发育异常，导致特征性龙虾样畸形。^[1]
• The diaphragmatic hernia results from failure of the diaphragm to close properly during development, allowing abdominal organs to enter the chest膈疝源于发育期间膈肌未能正确闭合，使腹部器官进入胸腔。^[1]
• Agenesis of the corpus callosum results from abnormal development of the commissural fibres connecting the cerebral hemispheres胼胝体发育不全源于连接大脑半球的连合纤维发育异常。^[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]
• Cardiac septal defects, when present, reflect abnormal development of the heart during embryogenesis当存在时，心脏间隔缺损反映胚胎发生期间心脏发育异常。^[1]

Clinical features

• The cardinal features are ectrodactyly (lobster-claw hands), diaphragmatic hernia and absence of the corpus callosum主要特征是并指畸形（龙虾样手）、膈疝和胼胝体缺失。^[1]
• Ectrodactyly presents as a deep median cleft of the hand with absence or fusion of central digits, giving a lobster-claw appearance并指畸形表现为手部深正中裂，中央指缺失或融合，呈现龙虾样外观。^[1]
• Diaphragmatic hernia presents with respiratory distress in the neonatal period and may require surgical repair膈疝表现为新生儿期呼吸窘迫，可能需要手术修复。^[1]
• Agenesis of the corpus callosum may be asymptomatic or associated with developmental delay and seizures胼胝体发育不全可能无症状或伴有发育迟缓和癫痫发作。^[1]
• Additional features include abnormalities of the alimentary tract, cardiac septal defects and a low frontal hairline额外特征包括消化道异常、心脏间隔缺损和低前发际线。^[1]
• Complications include respiratory distress, stillbirth and neonatal death, which occur with significant frequency并发症包括呼吸窘迫、死产和新生儿死亡，发生率显著。^[1]

Diagnosis

• Diagnosis is based on the characteristic clinical combination of ectrodactyly, diaphragmatic hernia and agenesis of the corpus callosum诊断基于并指畸形、膈疝和胼胝体发育不全的特征性临床组合。^[1]
• Prenatal ultrasound may detect the limb anomalies and diaphragmatic hernia, and brain imaging can identify agenesis of the corpus callosum产前超声可检测肢体异常和膈疝，脑影像学可识别胼胝体发育不全。^[1]
• Echocardiography is used to assess for cardiac septal defects, and abdominal imaging may evaluate for alimentary tract abnormalities超声心动图用于评估心脏间隔缺损，腹部影像学可评估消化道异常。^[1]
• The differential diagnosis includes other ectrodactyly syndromes such as EEC syndrome and split-hand/split-foot malformation鉴别诊断包括其他并指畸形综合征，如 EEC 综合征和裂手/裂足畸形。^[1]
• Genetic counselling is recommended for affected families, although the causative gene has not been identified尽管致病基因尚未确定，仍建议对受累家庭进行遗传咨询。^[1]
• Chromosomal microarray analysis may be performed to exclude chromosomal abnormalities causing similar features可进行染色体微阵列分析以排除引起类似特征的染色体异常。^[1]

Management

• There is no cure for Saal Bulas syndrome, and management is supportive and multidisciplinarySaal Bulas 综合征目前无法治愈，管理是支持性和多学科的。^[1]
• Surgical repair of the diaphragmatic hernia is required in the neonatal period to relieve respiratory distress新生儿期需要手术修复膈疝以缓解呼吸窘迫。^[1]
• Surgical correction of ectrodactyly may be considered to improve function and appearance可考虑并指畸形的手术矫正以改善功能和外观。^[1]
• Cardiac septal defects may require surgical repair, and developmental support is important for managing developmental delay心脏间隔缺损可能需要手术修复，发育支持对于管理发育迟缓很重要。^[1]
• Multidisciplinary care involving paediatrics, surgery, cardiology and neurology is essential涉及儿科、外科、心脏科和神经科的多学科护理至关重要。^[1]
• The prognosis is guarded, with significant mortality from respiratory complications and neonatal death in severe cases预后谨慎，严重病例因呼吸并发症和新生儿死亡而有显著死亡率。^[1]

Research and controversies

• The causative gene for Saal Bulas syndrome has not been identified, and the genetic basis remains an area of active researchSaal Bulas 综合征的致病基因尚未确定，遗传基础仍是活跃的研究领域。^[1]
• The inheritance pattern of the syndrome has not been definitively established, with autosomal recessive inheritance being presumed该综合征的遗传模式尚未确定，推定常染色体隐性遗传。^[1]
• Whether Saal Bulas syndrome is a distinct entity or part of a spectrum of ectrodactyly syndromes is an area of discussionSaal Bulas 综合征是独立实体还是并指畸形综合征谱系的一部分是讨论领域。^[1]
• The long-term outcomes and quality of life for surviving patients are not well characterized存活患者的长期结局和生活质量尚未充分描述。^[1]
• Further research is needed to identify the genetic cause and develop targeted therapies需要进一步研究以确定遗传原因并开发靶向治疗。^[1]

^[1]