Brockmann Knut, Staudt Martin
Interdisciplinary Pediatric Center for Children with Developmental Disabilities and Severe Chronic Disorders, Children's Hospital,, University Medical Center, Göttingen, Germany
Center for Pediatric Palliative Care, Dr von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany
syndrome is characterized by moderate-to-profound developmental delay and intellectual disability, postnatal growth deficiency, congenital or postnatal microcephaly, hyperkinetic/dyskinetic movement disorder, hypotonia, neurobehavioral/psychiatric manifestations (motor stereotypies, impairment of social interaction, abnormal sleep patterns, unexplained episodes of crying, restlessness, and bruxism), feeding difficulties with poor weight gain, strabismus, seizures, spasticity, gastroesophageal reflux, and aspiration. Some individuals have cortical visual impairment, kyphosis, scoliosis, and/or abnormal breathing. Characteristic neuroimaging findings include corpus callosum anomalies (especially a marked, filiform thinning of the rostrum of the corpus callosum), a simplified gyral pattern, and hyperplasia of the fornices.
The diagnosis of syndrome is established in a proband with clinical and/or characteristic neuroimaging findings and a heterozygous pathogenic variant in identified by molecular genetic testing.
Developmental and educational support; consideration of anti-dyskinetic pharmacotherapy; treatment for seizures by an experienced neurologist; treatment of spasticity per orthopedist; physical medicine and rehabilitation, physical therapy, and occupational therapy to help avoid contractures and falls; anti-spasmodic pharmacotherapy; feeding therapy with gastrostomy tube placement as needed; standard treatment of gastroesophageal reflux; treatment for refractive errors and strabismus per ophthalmologist; standard treatments for scoliosis; social work and family support. At each visit, monitor developmental progress, educational needs, seizures, changes in tone, movement disorders, growth, nutritional status, and safety of oral intake; behavioral assessment for irritability and sleep issues; assess for evidence of gastroesophageal reflux, aspiration, and/or respiratory insufficiency; physical medicine, occupational therapy, physical therapy assessment for mobility and self-help skills; monitor for strabismus and need for low vision services per treating ophthalmologist; assess family needs.
syndrome is an autosomal dominant disorder typically caused by a pathogenic variant. Risk to future pregnancies is presumed to be low as the proband most likely has a pathogenic variant. There is, however, a recurrence risk to sibs based on the possibility of parental germline mosaicism. Given this risk, prenatal and preimplantation genetic testing may be considered.
该综合征的特点为中重度发育迟缓与智力残疾、出生后生长发育不足、先天性或出生后小头畸形、运动亢进/运动障碍性运动障碍、肌张力减退、神经行为/精神症状（运动刻板行为、社交互动受损、异常睡眠模式、不明原因的哭闹、烦躁不安和磨牙）、喂养困难且体重增加不佳、斜视、癫痫发作、痉挛、胃食管反流和误吸。部分个体有皮质视觉障碍、脊柱后凸、脊柱侧凸和/或异常呼吸。特征性神经影像学表现包括胼胝体异常（尤其是胼胝体嘴部明显的丝状变薄）、脑回模式简化和穹窿增生。
在具有临床和/或特征性神经影像学表现且经分子遗传学检测鉴定出 基因杂合致病变异的先证者中确立该综合征的诊断。
发育和教育支持；考虑使用抗运动障碍药物治疗；由经验丰富的神经科医生治疗癫痫发作；由骨科医生治疗痉挛；物理医学与康复、物理治疗和职业治疗以帮助避免挛缩和跌倒；抗痉挛药物治疗；必要时进行胃造瘘管置入的喂养治疗；胃食管反流的标准治疗；由眼科医生治疗屈光不正和斜视；脊柱侧凸的标准治疗；社会工作和家庭支持。每次就诊时，监测发育进展、教育需求、癫痫发作、肌张力变化、运动障碍、生长、营养状况以及经口摄入的安全性；对易怒和睡眠问题进行行为评估；评估胃食管反流、误吸和/或呼吸功能不全的证据；进行物理医学、职业治疗、物理治疗以评估运动能力和自助技能；根据治疗眼科医生的建议监测斜视和低视力服务需求；评估家庭需求。
该综合征是一种常染色体显性疾病，通常由 基因的致病变异引起。由于先证者很可能有 基因的致病变异，未来妊娠的风险据推测较低。然而，基于父母生殖系嵌合的可能性，同胞有复发风险。鉴于此风险，可考虑进行产前和植入前基因检测。
