Clinical characteristics: 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 RAI1. A recurrent 3.7-Mb duplication accounts for approximately two thirds of 17p11.2 duplications; approximately one third are non-recurrent duplications that encompass RAI1 and vary in size from 0.41 Mb to 19.7 Mb.
Management: Treatment of manifestations: 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.
Surveillance: 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.
Genetic counseling: PTLS is inherited in an autosomal dominant manner. The majority of affected individuals have a de novo 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.
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