Neurological phenotype of Potocki-Lupski syndrome

Am J Med Genet A. 2020 Oct;182(10):2317-2324. doi: 10.1002/ajmg.a.61789. Epub 2020 Aug 15.

Abstract

Potocki-Lupski syndrome is a condition mainly characterized by infantile hypotonia, developmental delay/intellectual disability (DD/ID), and congenital anomalies, caused by duplications of the 17p11.2 region, encompassing RAI1 gene. Its clinical presentation is extremely variable, especially for what concerns the cognitive level and the behavioral phenotype. Such aspects, as well as the dysmorphic/malformative ones, have been covered by previous studies; otherwise neurological features have never been systematically described. In order to delineate the neurological phenotype of Potocki-Lupski Syndrome, we collect an 8-patients cohort. Developmental milestones are delayed and a mild to moderate cognitive impairment is present in all patients, variably associated with features of autism spectrum disorder, behavioral disturb, and sleep disturb. Hypotonia appears a less frequent finding than what previously reported, while motor clumsiness/coordination impairment is frequent. EGG registration demonstrated a common pattern with excess of diffuse rhythmic activity in sleep phases or while the patient is falling asleep. Brain MRI did not reveal common anomalies, although unspecific white matter changes may be present. We discuss such findings and compare them to literature data, offering an overview on the neurological and cognitive-behavioral presentation of the syndrome.

Keywords: 17p11.2; EEG; Potocki–Lupski syndrome; developmental disability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / diagnostic imaging*
  • Abnormalities, Multiple / genetics
  • Abnormalities, Multiple / pathology
  • Adolescent
  • Child
  • Child, Preschool
  • Chromosome Disorders / diagnostic imaging*
  • Chromosome Disorders / genetics
  • Chromosome Disorders / pathology
  • Chromosome Duplication / genetics
  • Cognitive Dysfunction / diagnostic imaging
  • Comparative Genomic Hybridization
  • Developmental Disabilities / diagnostic imaging*
  • Developmental Disabilities / genetics
  • Developmental Disabilities / pathology
  • Electroencephalography
  • Female
  • Humans
  • Infant
  • Intellectual Disability / diagnostic imaging*
  • Intellectual Disability / genetics
  • Intellectual Disability / pathology
  • Magnetic Resonance Imaging
  • Male
  • Muscle Hypotonia / diagnostic imaging
  • Muscle Hypotonia / genetics
  • Muscle Hypotonia / pathology
  • Nervous System Diseases / diagnostic imaging*
  • Nervous System Diseases / genetics
  • Nervous System Diseases / pathology
  • Phenotype
  • Sleep / physiology*

Supplementary concepts

  • Potocki-Lupski syndrome