Potocki-Lupski syndrome


Recommended panel testing at Breda Genetics for this condition:

MLPA analysis – RAI1 gene (TAT: 15 days); aCGH (TAT: 6 weeks); EXOME D (TAT: 4 weeks).

chromosome-green-xsReciprocal to Smith-Magenis syndrome

Potocki-Lupski syndrome (PTLS – OMIM 610883), also known as chromosome 17p11.2 duplication syndrome, is a developmental disorder characterized by hypotonia, failure to thrive, pervasive developmental disorders with mild-to-severe mental retardation with possible language and cognitive impairment and frequent features of autistic spectrum disorder. Several types of congenital anomalies, including cardiac defects, are also included in the clinical spectrum. PTLS may go unrecognized until later in infancy or childhood.

NAHR as a cause of PTLS

PLoSBiol3.5.Fig7ChromosomesAluFishPTLS is caused in about 60% of cases by a microduplication in the chromosomomal region 17p11.2. Such microduplication is caused in about 70% of cases by Non Allelic Homologous Recombination (NAHR) between low-copy repeats (LCRs) and is reciprocal to the common recurrent 3.7-Mb microdeletion that causes Smith-Magenis syndrome (SMS), a syndrome which shows overlapping clinical features, though being generally more severe than PTLS. In all cases of PTLS the microduplication appears to contain at least the RAI1 gene, suggesting that this gene is mainly responsible for the phenotype (SMS is caused also by single nonsense or frame-shift mutations of the RAI1 gene, confirming that this is a highly dosage-sensitive gene).

Diagnostic options

All reported cases oF PTLS have occurred sporadically without differences in the parental origin of rearrangements. PTLS is typically diagnosed by array comparative genomic hybridization (CGH) analysis (but also MLPA kits are available to measure the dosage of RAI1). High-throughput technologies like exome sequencing powered with CNVs detection probes and algorithms may also be used to screen for PTLS. High-throughput technologies offer the advantage to screen for other chromosomal imbalances or genic mutations in case the screening of the PTLS critical region is negative.

Additional clinical findings

Some typical features of PTLS also include: mild dysmorphic facial features (triangular facies, smooth and flat philtrum, high-arched palate, frontal bossing, trigonocephaly, hypertelorism, mandibular and maxillary hypoplasia, submucous cleft palate, bifid uvula, wide nasal bridge, epicanthal folds, strabismus, large mouth, wide third phalanges on the hands, and increased gap between the first and second toes), behavioral abnormalities such as attention-deficit, hyperactivity and autism, short stature, dental abnormalities such as malocclusion and crowded teeth, obstructive and central sleep apnea, structural cardiovascular abnormalities, electroencephalogram (EEG) abnormalities, and hypermetropia.

Some other clinical stigmata, which are more commonly seen in the reciprocal Smith-Magenis syndrome, are usually absent or just rarely reported in PTLS and include: short stature, hearing impairment, otolaryngologic abnormalities, myopia, iris hamartomata, genitourinary anomalies, renal anomalies, scoliosis, and hypercholesterolemia.

Recommended panel testing at Breda Genetics for this condition:

MLPA analysis – RAI1 gene (TAT: 15 days); aCGH (TAT: 6 weeks); EXOME D (TAT: 4 weeks).


Potocki-Lupski Syndrome. Potocki L, Neira-Fresneda J, Yuan B. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. SourceGeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018. 2017 Aug 24. PMID: 28837307

An Update on Common Chromosome Microdeletion and Microduplication Syndromes. Goldenberg P. Pediatr Ann. 2018 May 1;47(5):e198-e203. PMID: 29750287

Inherited dup(17)(p11.2p11.2): expanding the phenotype of the Potocki-Lupski syndrome. Magoulas PL, Liu P, Gelowani V, Soler-Alfonso C, Kivuva EC, Lupski JR, Potocki L. Am J Med Genet A. 2014 Feb;164A(2):500-4. PMID: 24311450

A New Patient with Potocki-Lupski Syndrome: A Literature Review. Praticò AD, Falsaperla R, Rizzo R, Ruggieri M, Verrotti A, Pavone P. J Pediatr Genet. 2018 Mar;7(1):29-34. PMID: 29441219

Molecular mechanism for duplication 17p11.2- the homologous recombination reciprocal of the Smith-Magenis microdeletion. Potocki L, Chen KS, Park SS, Osterholm DE, Withers MA, Kimonis V, Summers AM, Meschino WS, Anyane-Yeboa K, Kashork CD, Shaffer LG, Lupski JR. Nat Genet. 2000 Jan;24(1):84-7. PMID: 10615134

Two patients with duplication of 17p11.2: the reciprocal of the Smith-Magenis syndrome deletion? Brown A, Phelan MC, Patil S, Crawford E, Rogers RC, Schwartz C. Am J Med Genet. 1996 May 17;63(2):373-7. PMID: 8725788

Characterization of Potocki-Lupski syndrome (dup(17)(p11.2p11.2)) and delineation of a dosage-sensitive critical interval that can convey an autism phenotype. Potocki L, Bi W, Treadwell-Deering D, Carvalho CM, Eifert A, Friedman EM, Glaze D, Krull K, Lee JA, Lewis RA, Mendoza-Londono R, Robbins-Furman P, Shaw C, Shi X, Weissenberger G, Withers M, Yatsenko SA, Zackai EH, Stankiewicz P, Lupski JR. Am J Hum Genet. 2007 Apr;80(4):633-49. PMID: 17357070

OMIM: 610883

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