方法:X是一名22个月大的白人男性婴儿,有复杂的病史,包括FBXO11突变的诊断,低张力,限制性肺病和轻度间歇性哮喘,喉气管软化症,阻塞性睡眠呼吸暂停(OSA)喂养困难与渴望的历史,胃食管反流病(GERD),和发育迟缓。X的医疗报告导致多次因急性疾病而导致呼吸衰竭的医疗入院,手术和治疗,包括胃空肠吻合术(GJ)管依赖,声门上成形术重塑上喉组织,以及夜间使用双相气道正压(BiPAP)和白天在基线时使用室内空气。此外,他的夜间活动特征是显著的激动,尖叫,哭泣,身体僵硬和肢体运动,呼吸暂停,嘴巴呼吸,不安的睡眠,尽管进行了上述OSA治疗,但仍难以在早晨醒来并伴有白天疲劳。无先天性心脏病或不明原因猝死病史。家族史是无贡献的,因为父母对FBXO11变体呈阴性。X的睡眠中断导致了X和他的照顾者的严重睡眠不足,他们整晚都在制定如何安慰他的策略。X经历了几次睡眠研究,从X的4个月大开始,在全国的几家儿童医院,以确定他的慢性睡眠障碍的原因,这产生了有限的信息和治疗成功。作为一个婴儿,X接受了医学检查,随后用质子泵抑制剂(PPI)治疗回流。12个月时,他被诊断为睡眠紊乱与肌阵挛性抽搐,并开始使用褪黑激素和加巴喷丁进行不自主运动。13个月时,加巴喷丁因为不耐受而断奶,15个月时,开始使用去甲替林和可乐定是因为症状恶化以潜在的神经性疼痛为目标.虽然他的大部分症状都是在晚上,他偶尔会有白天的尖叫,尤其是在经历疾病的时候。停止加巴喷丁和可乐定,因为去甲替林似乎最有效。17个月时,睡眠研究的结果导致了夜惊的诊断,和一些临床医生一致认为,X\的睡眠中断是行为的性质。此时,一位婴儿心理健康顾问代表家庭会见了一位睡眠心理学家,以支持家庭考虑系统性脱敏治疗,以增加对戴BiPAP口罩的耐受性,以及其他行为和睡眠卫生策略,多次尝试,导致功能改善有限。19个月时,X的多学科团队在氯硝西泮试验失败后重新考虑了夜间恐怖诊断,并寻求周期性肢体运动障碍(PLMD)的鉴别诊断。X再次试验了加巴喷丁,但这次只有夜间剂量,根据睡眠医学和精神病学建议。虽然这给夜间的困扰带来了一些暂时的缓解,尽管增加到年龄和体重的最高剂量(15mg/kg/剂量),这变得不那么有效,他22个月就断奶了.他从6个月大开始就开始补铁,并在22个月时接受了铁输注,因为铁蛋白水平持续低,睡眠中PLMD。24个月时,X在左乙拉西坦上短暂试验。虽然脑电图上没有癫痫发作的证据,选择该药物是针对非自主运动和癫痫发作的遗传风险.然而,这种药没有用。25个月时,运动障碍生理学家的评估导致夜间阵发性肌张力障碍的诊断,他开始服用巴氯芬,这提供了一些,但不能完全缓解夜间症状.父母报告说他有更多的“晚安”而不是“糟糕的夜晚”,\"但是\"糟糕的夜晚\"在没有已知的触发或救济的情况下,持续了几天。最近,X是通过一般遗传学评估的。进行了全外显子组测序(WES),揭示了FBXO11中的致病性从头变体,并为他的神经发育表型提供了可能的原因。然而,他有一些FBX011无法解释的特征;因此,对他的WES进行了重新分析,发现在RAF1中具有不确定意义的从头变异。因为RAF1的致病变异与扩张型心肌病和Noonan谱系障碍有关,建议在心脏遗传学诊所定期随访X.家庭与FBXO11社区有很好的联系,包括支持Facebook的团体。父母们分享说,他们不觉得X的呼吸问题和疼痛与其他FBXO11突变儿童的表型相符。X还参加了一项医疗儿童保育计划,以促进发展和社会情感功能,并接受学习,演讲,职业,物理,在出诊时进行喂养治疗。尽管在过去几个月中由于感染了许多病毒性疾病而缺席了一段时间,X继续在发展疗法方面取得进展,并在参与该计划时乐于参与。为了更好地了解X的医学和行为表现,应考虑哪些额外的诊断测试和治疗?慢性睡眠不足和压力对X的特征婴儿的行为和发育有什么影响?重要的心理社会考虑因素是什么,因为它与具有医学复杂性(CMC)的儿童有关。特别是为了支持X和他的家人,家庭,和X的生活质量和整体福祉?
X is a 22-month-old White male infant with a complex medical history, including diagnoses of FBXO11 mutation, hypotonia, restrictive lung disease and mild intermittent asthma, laryngotracheomalacia, obstructive sleep apnea (OSA), feeding difficulties with a history of aspiration, gastroesophageal reflux disease (GERD), and developmental delays. X\'s medical presentation has resulted in multiple prior medical admissions for respiratory failure due to acute illnesses, procedures and treatments including gastrojejunostomy (GJ) tube dependence, supraglottoplasty to reshape tissues of the upper larynx, and the use of biphasic positive airway pressure (BiPAP) at night and room air during the day when he is at baseline. In addition, he has nocturnal events characterized by significant agitation, screaming, crying, body stiffening and limb movements with pauses in breathing, mouth breathing, restless sleep, and difficulty waking in the morning with concomitant daytime fatigue despite above treatments for OSA. There is no history of congenital heart disease or sudden unexplained death. Family history is noncontributory because parents are negative for the FBXO11 variant.X\'s sleep disruption has led to significant sleep deficits for both X and his caregivers, who spend much of the night strategizing on how to console him. X has undergone several sleep studies, starting when X was aged 4 months, at several children\'s hospitals across the nation to determine the cause of his chronic sleep disturbance, which yielded limited information and treatment success. As an infant, X received a medical workup and was subsequently treated with a proton pump inhibitor (PPI) for reflux. At 12 months, he was diagnosed with disordered sleep with myoclonic jerks and started on melatonin and gabapentin for involuntary movements. At 13 months, gabapentin was weaned back because of intolerance, and at 15 months, nortriptyline and clonidine were started because of worsening symptoms to target potential neuropathic pain. While most of his symptoms were at night, he had occasional daytime screaming episodes, particularly when experiencing illness. Gabapentin and clonidine were stopped because nortriptyline seemed most effective.At 17 months, the results from a sleep study led to a diagnosis of night terrors, and several clinicians agreed that X\'s sleep disruption was behavioral in nature. At this time, an infant mental health consultant met with a sleep psychologist on the family\'s behalf to support family in considering systematic desensitization therapy to increase tolerance to wearing his BiPAP mask, as well as other behavioral and sleep hygiene strategies, which were tried on several occasions and again, resulted in limited improvement in functioning.At 19 months, X\'s multidisciplinary team reconsidered a night terror diagnosis after a failed trial of clonazepam and pursued a differential diagnosis of periodic limb movement disorder (PLMD). X trialed gabapentin again, but this time only a nighttime dose, per sleep medicine and psychiatry recommendation. While this brought some temporary relief from nighttime distress, despite increasing to the highest dose for age and weight (15 mg/kg/dose), this became less effective, and he was weaned off at 22 months. He had been on iron supplementation since age 6 months and received an iron infusion at 22 months because of persistently low ferritin levels and PLMD in sleep.At 24 months, X was briefly trialed on levetiracetam. While no evidence for seizures on EEG was present, this medication was chosen for involuntary movements and genetic risk for seizures. However, this medication was not useful. At 25 months, an evaluation with a movement disorder physiatrist resulted in a diagnosis of nocturnal paroxysmal dystonia, and he was started on baclofen, which has provided some, but not complete relief to nighttime symptoms. Parents are reporting he has more \"good nights\" than \"bad nights,\" but \"bad nights\" come in stretches of a few days in length with no known trigger or relief.Most recently, X was evaluated by general genetics. Whole exome sequencing (WES) was pursued which revealed a pathogenic de novo variant in FBXO11 and provides a likely cause for his neurodevelopmental phenotype. However, he has some features not explained by FBX011; thus, reanalysis of his WES was performed and revealed a de novo variant of uncertain significance in RAF1. Because pathogenic variants in RAF1 have been associated with dilated cardiomyopathy and Noonan spectrum disorder, it was recommended that X be followed periodically in a cardiac genetics clinic. Family is well connected into the FBXO11 community, including supportive Facebook groups. Parents have shared that they do not feel X\'s breathing issues and pain fit with the phenotype of other children with FBXO11 mutations.X is also enrolled in a medical child care program to facilitate development and social-emotional functioning and receives learning, speech, occupational, physical, and feeding therapy while in attendance. Despite periods of absence due to contracting numerous viral illnesses over the past several months, X continues to make progress across developmental therapies and happily engages when at the program.What additional diagnostic tests and treatment should be considered to better understand X\'s medical and behavioral presentation? What are the implications of chronic sleep deprivation and stress on the behavior and development of infant with X\'s profile? What are important psychosocial considerations because it relates to children with medical complexity (CMC), particularly for X and his family to support caregiver, family, and X\'s quality of life and overall well-being?