Impacts of the diagnosis of leprosy and of visible impairments amongst people affected by leprosy in Cebu, the Philippines.

PURPOSE: To quantify the impact of the diagnosis of leprosy and of visible impairments in people affected by leprosy. SUBJECTS AND METHODS: Three interview-based questionnaires designed to measure activity limitation, participation restriction, and general self-efficacy were used to collect data from three Groups. Group 1: leprosy affected people with visible impairment, Group 2: newly diagnosed leprosy patients with no visible impairment, Group 3: patients with other skin diseases symptomatic for more than 1 month. RESULTS: One hundred and eight subjects were recruited. The subjects with visible impairments (Group 1) had higher levels of participation restriction than those with skin disease (P0.012), and participation restriction was similar between subjects in Groups 2 and 3 (P0-305). The people in Group 1 (35 subjects) also reported significantly more activity limitation compared to the people in either Group 2 (35 subjects) or Group 3 (38 subjects) (P 0-001, respectively). The subjects in Group 2 had no significant activity limitation compared with those in Group 3 (P0.338). A multivariate analysis showed that severe visible impairment was a risk factor for activity limitation (odds ratio 5.68, 95% CI: 1.09-297, P0.039) and a low level of self-efficacy (Odds ratio 6.38, 95% CI: 1.06-38.3, P0-043) among people affected by leprosy. CONCLUSION: Visible impairments affected the activities and attitudes of people affected by leprosy. However, others without visible impairment, had activity limitations, participation restrictions and levels of general self-efficacy that were similar to patients with other skin diseases. Prevention of visible impairments should be considered a key intervention for stigma reduction

DYRK1A haploinsufficiency causes a new recognizable syndrome with microcephaly, intellectual disability, speech impairment, and distinct facies

Dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A ) is a highly conserved gene located in the Down syndrome critical region. It has an important role in early development and regulation of neuronal proliferation. Microdeletions of chromosome 21q22.12q22.3 that include DYRK1A (21q22.13) are rare and only a few pathogenic single-nucleotide variants (SNVs) in the DYRK1A gene have been described, so as of yet, the landscape of DYRK1A disruptions and their associated phenotype has not been fully explored. We have identified 14 individuals with de novo heterozygous variants of DYRK1A; five with microdeletions, three with small insertions or deletions (INDELs) and six with deleterious SNVs. The analysis of our cohort and comparison with published cases reveals that phenotypes are consistent among individuals with the 21q22.12q22.3 microdeletion and those with translocation, SNVs, or INDELs within DYRK1A. All individuals shared congenital microcephaly at birth, intellectual disability, developmental delay, severe speech impairment, short stature, and distinct facial features. The severity of the microcephaly varied from −2 SD to −5 SD. Seizures, structural brain abnormalities, eye defects, ataxia/broad-based gait, intrauterine growth restriction, minor skeletal abnormalities, and feeding difficulties were present in two-thirds of all affected individuals. Our study demonstrates that haploinsufficiency of DYRK1A results in a new recognizable syndrome, which should be considered in individuals with Angelman syndrome-like features and distinct facial features. Our report represents the largest cohort of individuals with DYRK1A disruptions to date, and is the first attempt to define consistent genotype–phenotype correlations among subjects with 21q22.13 microdeletions and DYRK1A SNVs or small INDELs