Case Report: Potocki-Lupski Syndrome in Five Siblings

Abstract

Potocki-Lupski syndrome (PTLS) is a rare developmental disorder resulting from the partial duplication of the short arm of chromosome 17. Affected children may have hypotonia, facial dysmorphism, or neurological abnormalities. PTLS is also frequently associated with failure to thrive due to swallowing difficulties or growth hormone deficiency. We report the first Romanian family (a mother and her five children) diagnosed with PTLS (17p11.2 microduplication). Fortunately, they present a less severe form of the disease. The neurological manifestations (speech delay, mild intellectual disability) are associated with craniofacial dysmorphism (microcephaly, micrognathia, triangular face, broad forehead, long chin, prominent ears, dolichocephaly, down slanting palpebral fissures). The diagnostic was established using a multiplex ligation-dependent probe amplification technique (MLPA) test, which detected the duplication of three regions of the 17p11.2 chromosome (RAI1, DRC3-6, LLGL1-4RA). Children with PTLS have specific phenotypes (craniofacial dysmorphism or neurological manifestations), which must draw the pediatrician's attention to a possible genetic condition. However, every child with this disease is unique and may have a different clinical presentation. A multi-disciplinary team is needed for the management of these patients. The parent's counseling and genetic advice are essential for a family with children with PTLS.

A unique Smith-Magenis patient with a de novo intragenic deletion on the maternally inherited overexpressed RAI1 allele

“…However, the lack of other physical and neurobehavioral features did not lead to a PTLS diagnosis, which has never been suspected for her son. The lack of PTLS clinical diagnosis may be accounted for by the broad phenotype variability of the syndrome as previously reported [ 13 – 16 ]. However, we cannot exclude that RAI1 overexpression identified in blood might be tissue-specific and therefore not present in other tissues, particularly the nervous system, a scenario which might also explain the lack of a PTLS phenotype in the patient’s brother and mother.…”

“…Around 67% of PTLS patients harbor the recurrent 3.7 Mb microduplication and the remainder ones carry either larger or smaller non-recurrent duplications, involving the entire RAI1 gene [ 6 , 9 ] leading to its over-dosage. SMS deletions and PTLS duplications are de novo; however, a few familial cases of inherited SMS and PTLS are reported, showing a wide clinical expressivity [ 10 – 16 ]. Some SMS cases of maternal mosaicism are known [ 10 , 11 ].…”

“…Moreover, Acquaviva et al in 2017 reported for the first time an SMS patient, harboring a RAI1 frameshift mutation, generating offspring with the same alteration [ 12 ]. To date, four PTLS families with the common recurrent duplication have been reported [ 13 , 14 , 16 ]. Of note, in all families the 17p11.2 duplication was maternally transmitted and in a recent paper Grama et al described a mother and her five children, with a less severe form of the disease, confirming a wide clinical expressivity [ 16 ].…”

“…To date, four PTLS families with the common recurrent duplication have been reported [ 13 , 14 , 16 ]. Of note, in all families the 17p11.2 duplication was maternally transmitted and in a recent paper Grama et al described a mother and her five children, with a less severe form of the disease, confirming a wide clinical expressivity [ 16 ].…”

Potocki-Lupski Syndrome in Ethiopian Child: A Case Report

“…While this duplicated region may include multiple genes, it is RAI1 that primarily contributes to the key features of PTLS. 5 To the best of our knowledge, this is the initial case report documenting the diagnosis of PTLS in Ethiopia through the application of multiplex ligation probe amplification (MLPA).…”