Renata Rizzo

Background/Objectives: Pathogenic variants in the deleted in colorectal cancer gene (DCC), encoding the Netrin-1 receptor, may lead to mirror movements (MMs) associated with agenesis/dysgenesis of the corpus callosum (ACC) and cognitive and/or neuropsychiatric issues. The clinical phenotype is related to the biological function of DCC in the corpus callosum and corticospinal tract development as Netrin-1 is implicated in the guidance of developing axons toward the midline. We report on a child with a novel inherited, monoallelic, pathogenic variant in the DCC gene. Methods: Standardized measures and clinical scales were used to assess psychomotor development, communication and social skills, emotional and behavioural difficulties. MMs were measured via the Woods and Teuber classification. Exome sequencing was performed on affected and healthy family members. Results: The patient’s clinical presentation during infancy consisted of paroxysmal dystonic posturing when asleep, mimicking nocturnal leg cramps. A brain magnetic resonance imaging (MRI) showed complete ACC. He developed typical upper limb MMs during childhood and a progressively evolving neuro-phenotype with global development delay and behavioural problems. We found an intrafamilial clinical variability associated with DCC mutations: the proband’s father and uncle shared the same DCC variant, with a milder clinical phenotype. The atypical early clinical presentation of the present patient expands the clinical spectrum associated with DCC variants, especially those in the paediatric age. Conclusions: This study underlines the importance of in-depth genetic investigations in young children with ACC and highlights the need for further detailed analyses of early motor symptoms in infants with DCC mutations.

The chromosome 17q21.31 microduplication syndrome is a rare genetic syndrome presenting with craniofacial dysmorphisms, psychomotor delay, microcephaly, behavioral disorders, and poor social interaction. Only ten patients have been reported in the literature until today. All patients share some specific features, including psychomotor delay, behavioral disorders, and autism spectrum disorder (ASD). Here, a new case of this syndrome is reported in an 11-year-old Caucasian child who presented the classical clinical features of the 17q21.31 microduplication syndrome in association with new clinical characteristics previously unreported. The Array-Comparative Genomic Hybridization (aCGH) revealed a partial duplication of the long arm of chromosome 17. A literature review of previously studied patients with 17q21.31 microduplication syndrome is reported.