Refining the phenotype of SINO syndrome: A comprehensive cohort report of 14 novel cases.

Purpose: Spastic paraplegia, intellectual disability, nystagmus, and obesity syndrome (SINO) is a rare autosomal dominant condition caused by heterozygous variants in KIDINS220. A total of 12 individuals are reported, comprising 8 with SINO and 4 with an autosomal recessive condition attributed to biallelic KIDINS220 variants.

Methods: In our international cohort, we have included 14 individuals, carrying 13 novel pathogenic KIDINS220 variants in heterozygous form.

De novo variants in EMC1 lead to neurodevelopmental delay and cerebellar degeneration and affect glial function in Drosophila.

Background: The endoplasmic reticulum (ER)-membrane protein complex (EMC) is a multi-protein transmembrane complex composed of 10 subunits that functions as a membrane-protein chaperone. Variants in EMC1 lead to neurodevelopmental delay and cerebellar degeneration. Multiple families with biallelic variants have been published, yet to date, only a single report of a monoallelic variant has been described, and functional evidence is sparse.

Caregiver Perspectives on a Child's Diagnosis of 3q29 Deletion: "We Can't Just Wish This Thing Away".

Objective: Genetic diagnoses are increasingly common in cases of intellectual disability and developmental delay. Although ascertainment of a relatively common, well-studied variant may provide guidance related to treatments and developmental expectations, it is less clear how the diagnosis of a rare variant affects caregivers, especially when the phenotype may include later-onset manifestations such as psychosis. In this study, we sought to identify caregiver concerns in the first qualitative study to assess the psychosocial impact of diagnosis on caregivers of individuals with 3q29 deletion syndrome (3q29Del), which is associated with a 40-fold increase in risk for psychosis.

Novel features of 3q29 deletion syndrome: Results from the 3q29 registry.

3q29 deletion syndrome is caused by a recurrent, typically de novo heterozygous 1.6 Mb deletion, but because incidence of the deletion is rare (1 in 30,000 births) the phenotype is not well described. To characterize the range of phenotypic manifestations associated with 3q29 deletion syndrome, we have developed an online registry (3q29deletion.