Potocki Lorraine, Neira-Fresneda Juanita, Yuan Bo
Baylor College of Medicine, Houston, Texas
Potocki-Lupski syndrome (PTLS) is characterized by cognitive, behavioral, and medical manifestations. Cognitively, most individuals present with developmental delay, later meeting criteria for moderate intellectual disability. Behaviorally, issues with attention, hyperactivity, withdrawal, and anxiety may be seen. Some individuals meet criteria for autism spectrum disorder. Medically, hypotonia, oropharyngeal dysphagia leading to failure to thrive, congenital heart disease, hypoglycemia associated with growth hormone deficiency, and mildly dysmorphic facial features are observed. Medical manifestations typically lead to identification of PTLS in infancy; however, those with only behavioral and cognitive manifestations may be identified in later childhood.
DIAGNOSIS/TESTING: The diagnosis of PTLS is established by detection of a heterozygous duplication at chromosome 17p11.2 that encompasses . A recurrent 3.7-Mb duplication accounts for approximately two thirds of 17p11.2 duplications; approximately one third are non-recurrent duplications that encompass and vary in size from 0.41 Mb to 19.7 Mb.
A multidisciplinary evaluation involving healthcare providers from multiple specialties varies by the age and presenting issues of each individual. Management of all manifestations of PTLS is per standard care. Routine monitoring for growth deceleration, short stature, failure to thrive; periodic developmental assessment by a developmental specialist; screen for behavior problems at every visit; consultation with a psychiatrist and/or psychologist if there are behavioral concerns; follow up of congenital heart disease as per cardiac consultant.
PTLS is inherited in an autosomal dominant manner. The majority of affected individuals have a duplication; however, parent-to-child transmission has been reported. If the 17p11.2 duplication identified in the proband is not identified in either parent, the risk for future pregnancies could be slightly greater than that of the general population (though still <1%) because of the possibility of parental somatic and or germline mosaicism for the duplication. If one of the parents has the 17p11.2 duplication, the risk to each sib of inheriting the duplication is 50%. It is not possible to reliably predict the phenotype of individuals who inherit the duplication. Prenatal testing and preimplantation genetic testing using chromosomal microarray (CMA) to detect the 17q11.2 duplication found in the proband are possible.
波托基-卢普斯基综合征（PTLS）的特征在于认知、行为和医学表现。在认知方面，大多数个体存在发育迟缓，随后符合中度智力残疾的标准。在行为方面，可能会出现注意力、多动、退缩和焦虑问题。一些个体符合自闭症谱系障碍的标准。在医学方面，观察到肌张力减退、口咽吞咽困难导致生长发育不良、先天性心脏病、与生长激素缺乏相关的低血糖以及轻度面部畸形特征。医学表现通常导致在婴儿期确诊PTLS；然而，那些只有行为和认知表现的个体可能在儿童后期被确诊。
诊断/检测：PTLS的诊断通过检测17p11.2染色体上的杂合重复来确定，该重复包含……。一个反复出现的3.7兆碱基重复约占17p11.2重复的三分之二；约三分之一是非反复出现的重复，包含……，大小从0.41兆碱基到19.7兆碱基不等。
由来自多个专业的医疗保健提供者进行的多学科评估因每个个体的年龄和呈现的问题而异。PTLS所有表现的管理均按照标准护理进行。定期监测生长发育迟缓、身材矮小、生长发育不良；由发育专家进行定期发育评估；每次就诊时筛查行为问题；如果存在行为问题，咨询精神科医生和/或心理学家；按照心脏科顾问的建议对先天性心脏病进行随访。
PTLS以常染色体显性方式遗传。大多数受影响个体存在……重复；然而，也有亲子传播的报道。如果在先证者中发现的17p11.2重复在父母任何一方中未被发现，由于父母体细胞和/或生殖系嵌合该重复的可能性，未来妊娠的风险可能略高于一般人群（尽管仍<1%）。如果父母一方有17p11.2重复，每个兄弟姐妹继承该重复的风险为50%。无法可靠预测继承该重复的个体的表型。使用染色体微阵列（CMA）进行产前检测和植入前基因检测以检测先证者中发现的17q11.2重复是可行的。
