Al Kaissi Ali, Ryabykh Sergey, Chehida Farid Ben, Al Kaissi Hamza, Kircher Susanne Gerit, Grill Franz, Guben Alexander
National Medical Research Center for Traumatology and Orthopedics n.a. G.A. Ilizarov, 640014 Kurgan, Russia.
Ibn Zohr Institute of Diagnostic Radiology, Cite Al Khadra, Tunis 1003, Tunisia.
Children (Basel). 2023 Jul 18;10(7):1240. doi: 10.3390/children10071240.
Omitting the early closure of the cranial sutures in newly born children is not an uncommon practice. We describe the natural history of several unrelated children and adults from two unrelated families. These children were born with variable clinical manifestations: craniofacial asymmetry, ocular proptosis, floppiness, and progressive deceleration in cognitive development. None of these children underwent a cranial sutures assessment. False diagnoses of positional plagiocephaly, neonatal thyrotoxicosis, congenital muscular atrophy, and hydrocephalus were given to the parents. This sort of malpractice was the reason behind a sequence of devastating pathological events that occurred in the lifetime of these children and adults.
This was a multigenerational study of two unrelated families. In total, we studied three children (aged 7-19 years) and three adults (aged 40-52 years) from two families. The children from the first family were referred to our departments because of pre-pubertal scoliosis, kyphoscoliosis, and early-onset osteoarthritis. Reading the clinical histories of these children signified apparent clinical misconceptions. For instance, craniofacial asymmetry was misinterpreted as positional plagiocephaly and treated by means of helmet molding therapy. Ocular proptosis was given the false diagnosis of neonatal thyrotoxicosis. Floppiness (hypotonia) was misdiagnosed as congenital muscular dystrophy. The index case from the second family showed progressive deceleration in his cognitive development, associated with signs of increased intracranial pressure. The only diagnosis was Dandy-Walker malformation. We documented every patient in accordance with the clinical and radiological phenotypic characterizations. The genotype characterization followed accordingly.
All patients in family (I) manifested a phenotype consistent to a certain extent with the clinical phenotype of Shprintzen-Goldberg syndrome (SGS), though the intensity of spine deformities was greater than has been described in the literature. The second family showed a constellation of Marfanoid habitus, craniosynostosis, increased intracranial pressure, hydrocephalus, Dandy-Walker malformation, seizures, and intellectual disability. The overall clinical phenotype was consistent but not fully diagnostic of craniosynostosis-Dandy-Walker-malformation hydrocephalus syndrome. The early closure of the sutures was totally different from one patient to another, including the premature closure of the metopic, coronal, squamosal, and sagittal sutures. One patient from family (II) underwent the implementation of a shunt system at the age of 3 years, unfortunately passing over the pre-existing craniosynostosis. In addition to skeletal deformities, a history of seizures and severe intellectual disability was recorded. The proband underwent chromosomal karyotyping, the FISH test, and whole-exome sequencing.
The purpose of this study was fivefold. Firstly, to gain a meticulous understanding in order to differentiate between positional plagiocephaly, hypotonia, and congenital exophthalmos and their connections to abnormal craniofacial contours was and still is our first and foremost concern. Secondly, we aimed to characterize craniosynostosis, seizures, intellectual disabilities, and hydrocephalus associated with Marfanoid habitus, which were clearly demonstrated in our patients. Thirdly, we aimed to address the imperative for interpretations of clinical and radiological phenotypes and relate these tools to etiological understanding, which is an essential basis for diagnosis in the majority of long-term pediatric admissions. Fourthly, we aimed to assess the impacts of the missed early closure by the pediatricians and pediatric neurologists, which added a heavy pathological burden on these patients and their families. Fifthly, we aimed to identify whether early and diligent recognition can assist in cranial vault remodeling via surgical intervention to halt premature cranial suture fusions and can possibly alter the devastating course and the complications of the synostosed sutures.
在新生儿中忽略早期颅骨缝闭合并非罕见的情况。我们描述了来自两个无关家庭的几名不相关儿童和成人的自然病史。这些儿童出生时具有不同的临床表现：颅面不对称、眼球突出、肌张力低下以及认知发育逐渐减速。这些儿童均未接受颅骨缝评估。家长们曾被误诊为体位性斜头畸形、新生儿甲状腺毒症、先天性肌肉萎缩和脑积水。这种医疗失误是这些儿童和成人一生中一系列灾难性病理事件的背后原因。
这是一项对两个无关家庭的多代研究。我们总共研究了来自两个家庭的三名儿童（7 - 19岁）和三名成人（40 - 52岁）。第一个家庭的儿童因青春期前脊柱侧弯、脊柱后凸侧弯和早发性骨关节炎被转诊至我们科室。阅读这些儿童的临床病史表明存在明显的临床误解。例如，颅面不对称被误判为体位性斜头畸形并采用头盔塑形疗法治疗。眼球突出被误诊为新生儿甲状腺毒症。肌张力低下（松软）被误诊为先天性肌肉营养不良。第二个家庭的索引病例表现出认知发育逐渐减速，并伴有颅内压升高的迹象。唯一的诊断是丹迪 - 沃克畸形。我们根据临床和放射学表型特征记录了每一位患者。随后进行了基因型特征分析。
家族（I）中的所有患者在一定程度上表现出与施普林曾 - 戈德堡综合征（SGS）临床表型一致的表型，尽管脊柱畸形的严重程度大于文献中所描述的情况。第二个家庭表现出一系列马凡氏体型、颅缝早闭、颅内压升高、脑积水、丹迪 - 沃克畸形、癫痫发作和智力残疾。总体临床表型一致，但并不完全诊断为颅缝早闭 - 丹迪 - 沃克畸形 - 脑积水综合征。缝线的早期闭合在不同患者之间完全不同，包括额缝、冠状缝、鳞状缝和矢状缝的过早闭合。家族（II）中的一名患者在3岁时接受了分流系统植入手术，不幸的是忽略了已存在的颅缝早闭。除了骨骼畸形外，还记录有癫痫发作史和严重智力残疾。先证者接受了染色体核型分析、荧光原位杂交（FISH）检测和全外显子测序。
本研究的目的有五个方面。首先，为了深入细致地理解以便区分体位性斜头畸形、肌张力低下和先天性眼球突出及其与异常颅面轮廓的关联，这过去是且现在仍然是我们首要关注的问题。其次，我们旨在描述与马凡氏体型相关的颅缝早闭、癫痫发作、智力残疾和脑积水，这些在我们的患者中得到了明确体现。第三，我们旨在强调对临床和放射学表型进行解读的必要性，并将这些工具与病因学理解联系起来，这是大多数长期儿科住院患者诊断的重要依据。第四，我们旨在评估儿科医生和儿科神经科医生错过早期闭合诊断所带来的影响，这给这些患者及其家庭增加了沉重的病理负担。第五，我们旨在确定早期且认真的识别是否能够通过手术干预协助颅骨重塑，以阻止颅骨缝过早融合，并有可能改变已融合缝线的灾难性病程和并发症。
