Zechi-Ceide syndrome

Zechi–Ceide syndrome is an ultra-rare multiple congenital anomalies syndrome defined by an occipital atretic cephalocele, distinctive facial features, severe oligodontia, large wide feet and cerebellar vermis hypoplasia, often accompanied by developmental delay.Zechi–Ceide 综合征是一种极罕见的多发先天畸形综合征，以枕部闭锁性脑膜脑膨出、特殊面容、严重少牙畸形、宽大双足及小脑蚓部发育不良为特征，常伴发育迟缓。

The condition was delineated in 2007 in three Brazilian siblings born to consanguineous parents, and only one further patient has been reported since, so both the phenotypic spectrum and the molecular basis remain incompletely defined.该病于 2007 年在巴西一个近亲婚配家系的三个同胞中被界定，此后仅再报告一例患者，因此其表型谱与分子基础均未完全明确。

Terminology and classification

• The eponym Zechi–Ceide syndrome honours the clinical geneticists who described the index family in 2007.Zechi–Ceide 综合征这一人名名称纪念于 2007 年描述该家系的临床遗传学家。
• Orphanet registers ORPHA:217017 under a descriptive label that lists the occipital atretic cephalocele, unusual facies and large feet, and that label is useful when the eponym is unfamiliar.Orphanet 将 ORPHA:217017 登记在描述性名称之下，列出枕部闭锁性脑膜脑膨出、特殊面容与宽大双足，在人名名称不熟悉时该描述性名称更为实用。
• OMIM assigns phenotype number 612916, MONDO uses MONDO:0013036 and Orphanet uses ORPHA:217017, and all three identifiers point to the same entity.OMIM 将该表型编为 612916，MONDO 编为 MONDO:0013036，Orphanet 编为 ORPHA:217017，三套标识指向同一实体。
• MeSH catalogues the disorder as C567865, UMLS as C2752047, GARD as 10582 and SNOMED CT as 773307006, while Wikidata holds Q22978786.MeSH 编为 C567865，UMLS 编为 C2752047，GARD 编为 10582，SNOMED CT 编为 773307006，Wikidata 则为 Q22978786。
• ICD-10 has no specific code and the condition is placed in Q87.8, whereas ICD-11 maps it to LD2F.1Y among other specified developmental anomalies.ICD-10 无专属编码，该病被归入 Q87.8，而 ICD-11 将其映射至 LD2F.1Y，列于其他特指的发育异常之中。
• An atretic cephalocele is a small skin-covered midline mass connected to the dura by a fibrous stalk, and by definition it contains no herniated brain tissue.闭锁性脑膜脑膨出是一种小的、被皮肤覆盖的中线肿块，通过纤维蒂与硬脑膜相连，按定义不含疝出的脑组织。
• The syndrome is grouped with midline craniocerebral malformation syndromes rather than with open neural tube defects, because the cranial defect is closed by skin.该综合征被归入中线颅脑畸形综合征，而非开放性神经管缺陷，因为颅骨缺损已被皮肤覆盖闭合。
• It should not be confused with a classic occipital encephalocele, in which meninges or brain tissue protrude through a bony defect and the risk of hydrocephalus and infection is far higher.该病不应与典型枕部脑膜脑膨出混淆，后者有脑膜或脑组织经骨缺损突出，脑积水与感染的风险高得多。

History

• Zechi-Ceide and colleagues reported the syndrome in 2007 in the American Journal of Medical Genetics Part A, describing three affected siblings from Bauru, Brazil.Zechi-Ceide 及其同事于 2007 年在《美国医学遗传学杂志 A 辑》报告该综合征，描述了来自巴西包鲁的三个受累同胞。^[1]
• All three children were born to consanguineous parents, and the pedigree was consistent with autosomal recessive inheritance.三个患儿均出生于近亲婚配的父母，家系图符合常染色体隐性遗传。
• Each affected child had an occipital atretic cephalocele, a prominent forehead, midface deficiency, a broad nose, severe oligodontia and large feet with a wide gap between the first and second toes.每个受累儿童均有枕部闭锁性脑膜脑膨出、前额突出、面中部发育不足、宽鼻、严重少牙畸形以及伴第一二趾宽间隙的大足。
• Cerebellar vermis hypoplasia and developmental delay were also present, and the authors emphasised that the facial appearance was distinctive enough to suggest a new syndrome.患儿还伴小脑蚓部发育不良与发育迟缓，作者强调其面容具有足够特征性，提示为一个新综合征。
• In 2012 Patil and colleagues reported a second patient from Bangalore and noted that the child's mother had minor facial features, which complicated the inheritance model.2012 年 Patil 及其同事报告了来自班加罗尔的第二例患者，并指出患儿母亲具有轻微面部特征，使遗传模式判断变得复杂。^[2]
• No further patients, case series or molecular studies have appeared since that report, so the literature still rests on four affected individuals.该报告之后未见更多患者、病例系列或分子研究，因此文献仍仅基于四名受累者。

Epidemiology

• Orphanet estimates a prevalence below 1 per 1,000,000 and records only three cases, reflecting the rarity of published reports rather than a measured population rate.Orphanet 估计患病率低于百万分之一，仅记录三例，这反映的是已发表报告的稀少，而非实测的人群发生率。
• Four affected individuals have been described in the literature, namely three siblings from Brazil and one child from India.文献共描述四名受累者，即来自巴西的三个同胞与来自印度的一名儿童。
• The index family was consanguineous, and the affected siblings imply a 25 percent recurrence risk under autosomal recessive inheritance.先证家系为近亲婚配，受累同胞在常染色体隐性遗传下意味着 25% 的复发风险。
• Reports from South America and South Asia show no evidence of a geographic or ethnic restriction.来自南美洲与南亚洲的报告未显示地理或种族限制的证据。
• Orphanet records onset in infancy or the neonatal period, which matches the congenital nature of the cephalocele and the early recognition of dysmorphic features.Orphanet 记录发病于婴儿期或新生儿期，这与脑膜脑膨出的先天性本质及面容异常的早期识别相符。
• No sex bias has been documented, although the published numbers are far too small to exclude one.尚无性别偏倚的记录，但已发表例数过少，无法排除其存在。
• Mildly affected individuals may never reach a genetics clinic, so the true prevalence is probably higher than the published count suggests.轻症受累者可能从未就诊于遗传门诊，因此真实患病率很可能高于已发表例数所提示的水平。
• No mortality, morbidity or life-expectancy data have been published, and long-term follow-up of the reported patients is not available.尚无死亡率、发病率或预期寿命数据发表，已报告患者的长期随访资料亦不可得。

Pathophysiology

• The molecular cause is unknown, and no pathogenic variant, candidate gene or chromosomal locus has been established.分子病因未知，尚未确定致病性变异、候选基因或染色体位点。
• Autosomal recessive inheritance is the most economical explanation for three affected siblings born to consanguineous parents.常染色体隐性遗传是解释近亲婚配父母所生三个受累同胞的最简约假说。
• Patil and colleagues also considered autosomal dominant inheritance with variable expression, X-linked inheritance and a manifesting carrier state, because the mother of their patient had subtle facial features.由于患者母亲具有轻微面部特征，Patil 及其同事还考虑了表现度可变的常染色体显性遗传、X 连锁遗传以及携带者表现型。
• The combination of a midline cranial closure defect, dental agenesis, ear anomalies and facial hypoplasia suggests disruption of a shared developmental field involving neural crest derivatives.中线颅骨闭合缺陷、牙齿缺失、耳畸形与面部发育不良的组合提示累及神经嵴衍生结构的共同发育场受到干扰。
• Cerebellar vermis hypoplasia points to disturbed hindbrain development in early gestation, and it is a malformation rather than a progressive lesion.小脑蚓部发育不良提示妊娠早期后脑发育受到干扰，属于畸形而非进展性病变。
• An atretic cephalocele is thought to arise from a localised mesenchymal defect that leaves a fibrous stalk connecting skin to dura, sometimes with an underlying venous anomaly.闭锁性脑膜脑膨出被认为源于局部间充质缺陷，遗留连接皮肤与硬脑膜的纤维蒂，有时伴其下的静脉异常。
• Karyotypes and routine metabolic investigations have been normal in reported patients, which argues against a large chromosomal rearrangement or an inborn error of metabolism.已报告患者的核型与常规代谢检查均正常，这不支持大片段染色体重排或先天性代谢缺陷。

Clinical features

• The occipital atretic cephalocele is a small skin-covered nodule in the midline of the occiput and may be mistaken at birth for a lipoma, a dermoid cyst or a scalp cyst.枕部闭锁性脑膜脑膨出是枕部中线的小型皮肤覆盖结节，出生时易被误认为脂肪瘤、皮样囊肿或头皮囊肿。
• Facial features include a prominent forehead, midface deficiency, a broad nasal root, a broad nose with a grooved tip, abnormally shaped nares and narrow malformed ears.面部特征包括前额突出、面中部发育不足、鼻根宽、鼻尖有沟的宽鼻、鼻孔形态异常以及狭窄畸形的耳。
• Severe oligodontia is a cardinal feature, with most permanent teeth missing and the primary dentition also affected in the reported children.严重少牙畸形是核心特征，已报告患儿多数恒牙缺失，乳牙列亦受累。
• The feet are large and broad, with an increased hallux-to-second-toe gap that is often called a sandal gap.双足大而宽，第一与第二趾间隙增宽，常称为凉鞋间隙。
• Cerebellar vermis hypoplasia or a Dandy–Walker variant may cause hypotonia, ataxia and delayed motor milestones.小脑蚓部发育不良或 Dandy–Walker 变异型可引起肌张力低下、共济失调与运动里程碑延迟。
• Global developmental delay and intellectual disability vary in severity, and the published descriptions are too few to define a typical cognitive profile.全面发育迟缓与智力障碍的严重程度不一，已发表描述过少，无法界定典型的认知特征。
• Additional features recorded by MedGen include narrow palpebral fissures, a short philtrum, a thin upper lip, cleft lip or palate, a prominent chin and hypoplastic finger and toe nails.MedGen 记录的附加特征包括睑裂狭窄、人中短、上唇薄、唇裂或腭裂、下巴突出以及手指甲与趾甲发育不全。
• Expressivity appears variable, since the mother of the Indian patient had only minor facial findings while her son had the full syndrome.表现度似有差异，印度患者的母亲仅有轻微面部表现，而其子具有完整综合征。

Diagnosis

• Diagnosis is clinical and rests on recognising the combination of an occipital atretic cephalocele, characteristic facies, severe oligodontia and large wide feet.诊断基于临床，依靠识别枕部闭锁性脑膜脑膨出、特殊面容、严重少牙畸形与宽大双足的组合。
• Brain MRI defines the cephalocele, its intracranial connection and the degree of cerebellar vermis hypoplasia, and it also excludes hydrocephalus and cortical malformations.脑部磁共振成像可界定脑膜脑膨出、其颅内连接及小脑蚓部发育不良程度，并排除脑积水与皮质畸形。
• A panoramic dental radiograph quantifies the number of missing teeth and helps plan rehabilitation.全景牙科 X 线片可量化缺失牙数，并有助于制定修复计划。
• Human Phenotype Ontology terms such as HP:0002084 for encephalocele, HP:0000677 for oligodontia, HP:0001833 for long foot, HP:0001852 for sandal gap, HP:0001263 for global developmental delay and HP:0001320 for cerebellar vermis hypoplasia allow structured recording.人类表型本体术语可用于结构化记录，例如脑膨出 HP:0002084、少牙 HP:0000677、长足 HP:0001833、凉鞋间隙 HP:0001852、全面发育迟缓 HP:0001263 与小脑蚓部发育不良 HP:0001320。
• Chromosomal microarray should be performed to exclude a contiguous deletion or duplication that could mimic the combination of midline and dental anomalies.应行染色体微阵列检测，以排除可模仿中线与牙齿异常组合的相邻基因缺失或重复。
• Exome or genome sequencing is reasonable in research settings, but a negative result does not exclude the syndrome because no causal gene is known.在研究环境中可行外显子组或基因组测序，但阴性结果不能排除该综合征，因为尚无已知致病基因。
• Joubert syndrome is distinguished by the molar tooth sign on MRI and by the absence of an atretic cephalocele, while Meckel–Gruber syndrome combines occipital encephalocele with polydactyly and cystic kidneys.Joubert 综合征以磁共振上的磨牙征及无闭锁性脑膜脑膨出相鉴别，而 Meckel–Gruber 综合征则将枕部脑膨出与多指及肾囊肿合并出现。
• Oral-facial-digital syndromes, Ellis–van Creveld syndrome, ectodermal dysplasia and Goldenhar syndrome each overlap with part of the phenotype but not with the full combination.口腔-面-指综合征、Ellis–van Creveld 综合征、外胚层发育不良与 Goldenhar 综合征各与部分表型重叠，但不符合完整组合。

Management

• There is no disease-specific therapy, and care is multidisciplinary and supportive.目前没有疾病特异性治疗，处理为多学科支持性照护。
• Neurosurgical assessment determines whether the atretic cephalocele needs repair, and surgery is usually considered for cosmetic reasons, recurrent trauma or a documented connection to the dura.神经外科评估决定闭锁性脑膜脑膨出是否需要修复，手术通常出于外观原因、反复外伤或证实与硬脑膜相连而考虑。
• Neurological follow-up with imaging is needed when hydrocephalus, a tethered cord or a venous anomaly is suspected.当怀疑脑积水、脊髓拴系或静脉异常时，需神经科随访并复查影像。
• Dental rehabilitation combines prosthodontics, removable appliances in childhood and implant-based reconstruction after facial growth is complete.牙齿修复结合修复学、儿童期可摘矫治器以及面部生长完成后的种植体修复。
• Cleft lip or palate requires surgical repair and subsequent speech and feeding therapy.唇裂或腭裂需手术修复，随后进行言语与喂养治疗。
• Hypotonia, ataxia and developmental delay warrant physiotherapy, occupational therapy and individualised educational support.肌张力低下、共济失调与发育迟缓需物理治疗、作业治疗与个体化教育支持。
• Genetic counselling should quote a 25 percent recurrence risk when autosomal recessive inheritance is assumed, and it should explain that carrier testing is unavailable without an identified gene.遗传咨询在假定常染色体隐性遗传时应给出 25% 的复发风险，并说明在未找到致病基因前无法进行携带者检测。
• Orthopaedic or podiatric review addresses the wide feet and gait problems, and growth, hearing and vision should be monitored at routine intervals.骨科或足病评估处理宽足与步态问题，生长、听力与视力应按常规间隔监测。

Research and controversies

• The highest priority is gene discovery, and the consanguineous index family is well suited to homozygosity mapping followed by exome sequencing if samples can be obtained.首要任务是发现致病基因，若能取得样本，近亲婚配的先证家系很适合先做纯合性定位再进行外显子组测序。
• Matchmaker Exchange or an undiagnosed diseases programme could connect the four published patients with unpublished cases and test whether they share a locus.Matchmaker Exchange 或未诊断疾病项目可将四名已发表患者与未发表病例联系起来，检验其是否共享同一基因位点。
• Whether the Indian patient reported in 2012 has the same disorder as the Brazilian siblings remains unproven, because the mother's mild features could indicate a different mechanism.2012 年报告的印度患者是否与巴西同胞患同一疾病仍未证实，因为其母亲的轻微特征可能提示不同机制。
• No interventional study for Zechi–Ceide syndrome is registered on ClinicalTrials.gov as of October 2026.截至 2026 年 10 月，ClinicalTrials.gov 未登记针对 Zechi–Ceide 综合征的干预性研究。
• The eponym and the descriptive Orphanet label coexist, and further reports with photographs, dental imaging and genetic data are needed before either name or the entity itself can be considered settled.人名名称与 Orphanet 描述性名称并存，需更多附照片、牙科影像与遗传数据的报告，才能使名称或疾病实体本身得以确定。