Clinical and genetic characteristics analysis of four cases of Phelan-McDermid syndrome caused by the novel mutations of the SHANK3 gene / 中华实用儿科临床杂志

The basic information and clinical data of 4 Phelan-McDermid syndrome (PMS) patients in the Pediatric Outpatient Department of the Peking University First Hospital from January 2014 to October 2019 were retrospectively analyzed.Genetic diagnoses were performed using the whole exon sequencing assay.The genotype-phenotype correlation analysis was then performed.All patients presented with intellectual disability/developmental delay, especially the most-common manifestation in language disability.Patient 2 had an autism behavior.Four novel variations of the SHANK3 gene were found in this study, including the c. 2861delC p. (S955Pfs*109), c.3166delC p. (A1039Afs*39), c.3711_3723delGCCCAGCCCCCGG p. (L1241Lfs*29) and c. 2223+ 1G>A.All of them were analyzed as new pathogenic variations according to the American College of Medical Genetics and Genomics criteria.The present study expan-ded the mutant spectrum of the SHANK3 gene, which provided a basis for further accurate genetic counseling and prenatal diagnosis of PMS.

Phelan-McDermid syndrome presenting with developmental delays and facial dysmorphisms / 소아과

Phelan-McDermid syndrome is a rare genetic disorder caused by the terminal or interstitial deletion of the chromosome 22q13.3. Patients with this syndrome usually have global developmental delay, hypotonia, and speech delays. Several putative genes such as the SHANK3, RAB, RABL2B, and IB2 are responsible for the neurological features. This study describes the clinical features and outcomes of Korean patients with Phelan-McDermid syndrome. Two patients showing global developmental delay, hypotonia, and speech delay were diagnosed with Phelan-McDermid syndrome via chromosome analysis, fluorescent in situ hybridization, and multiplex ligation-dependent probe amplification analysis. Brain magnetic resonance imaging of Patients 1 and 2 showed delayed myelination and severe communicating hydrocephalus, respectively. Electroencephalography in patient 2 showed high amplitude spike discharges from the left frontotemporoparietal area, but neither patient developed seizures. Kidney ultrasonography of both the patients revealed multicystic kidney disease and pelviectasis, respectively. Patient 2 experienced recurrent respiratory infections, and chest computed tomography findings demonstrated laryngotracheomalacia and bronchial narrowing. He subsequently died because of heart failure after a ventriculoperitoneal shunt operation at 5 months of age. Patient 1, who is currently 20 months old, has been undergoing rehabilitation therapy. However, global developmental delay was noted, as determines using the Korean Infant and Child Development test, the Denver developmental test, and the Bayley developmental test. This report describes the clinical features, outcomes, and molecular genetic characteristics of two Korean patients with Phelan-McDermid syndrome.