22q11.２欠失症候群

BACKGROUND: 22q11.2 deletion syndrome (22q11.2DS) may be overlooked in adults when neurological care is prompted by pyramidal, gait, or parkinsonism-mimicking presentations rather than by congenital, developmental, psychiatric, or systemic features. METHODS: We retrospectively reviewed the clinical, imaging, and genetic findings of two unrelated adults whose neurological presentations led to whole-exome sequencing-based copy-number variant (CNV) detection of 22q11.21 deletions. Orthogonal confirmation by chromosomal microarray, multiplex ligation-dependent probe amplification (MLPA), quantitative polymerase chain reaction (qPCR), fluorescence in situ hybridization (FISH), or copy-number variation sequencing (CNV-seq) was not available; therefore, the reported deletion sizes and coordinates represent WES-derived estimates. RESULTS: Patient 1 presented with progressive lower-limb weakness, a spastic unsteady gait, pyramidal signs, dysarthria, and ataxic features, together with learning difficulty, palatal abnormalities, and a maternal history of similar gait disturbance and suspected epilepsy; analysis identified a 2.67-Mb deletion at 22q11.21. Patient 2 presented with progressive limb weakness, dysarthria, parkinsonism-mimicking rigidity and slowness, bilateral basal ganglia calcification, abnormal globus pallidus MRI signals, developmental delay, psychiatric symptoms, craniofacial features, and a maternal history of similar motor and cognitive impairment; analysis identified a 2.52-Mb deletion at 22q11.21. CONCLUSION: These cases highlight diagnostic pitfalls and syndromic clues rather than establish a new mechanism. In adult neurology practice, developmental history, palatal or craniofacial abnormalities, basal ganglia calcification, psychiatric symptoms, and family history should prompt consideration of 22q11.2DS and genetic testing that is sensitive to copy-number variants.

OBJECTIVE: The study aimed to determine the distribution of congenital heart diseases (CHDs), associated congenital malformations, and syndromes among children with orofacial clefts (OFCs) at Tawanchai Cleft Center, Khon Kaen, Thailand from 2011 to 2020. METHODS: The retrospective study reviewed medical records of 1187 children with OFCs at a tertiary cleft center from 2011 to 2020. A total of 95 eligible cases met the following inclusion criteria: diagnosis of cleft palate (CP), cleft lip (CL), or cleft lip and palate (CLP); age from birth to 3 years; confirmed CHD diagnosis by a cardiologist; confirmed diagnosis of congenital malformations or syndromes by a geneticist; and complete medical records. Distributions were described using frequencies and percentages. Fisher's exact test and binary logistic regression (unadjusted and sex-adjusted) were used for inferential analysis. RESULTS: Among 95 patients, CP was the most frequent OFC type (48.4%), followed by CLP (44.2%) and CL (7.4%). The sex distribution was 48.4% male and 51.6% female, and all patients were of Thai ethnicity. The observed proportion of CHDs (8.0%) fell in the mid-range of prior studies. The most common CHDs were atrial septal defect (ASD, 25.3%), patent ductus arteriosus (PDA, 20.0%), and ventricular septal defect (VSD, 18.9%). Pierre Robin sequence (PRS) was the most common associated congenital malformation (10.4%). Syndromic clefts occurred in 38 cases (40.0%), predominantly involving 22q11.2 deletion syndrome (18.4%), vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb abnormalities association (13.1%), and Down syndrome (7.9%). Binary logistic regression revealed significantly lower odds of VSD in patients with unilateral CLP compared to those with CL (sex-adjusted odds ratio = 0.07, 95% confidence interval = 0.01-0.61, p = 0.02). CONCLUSION: ASD, PDA, and VSD are the most common CHDs among patients with OFCs. These CHDs frequently co-occur with PRS and 22q11.2 deletion syndrome. These findings underscore the importance of comprehensive cardiac screening in children with OFCs to support interdisciplinary cleft care management.

Dopaminergic signalling is critical for regulating large-scale brain network dynamics and is implicated in the pathophysiology of psychotic disorders. 22q11.2 deletion syndrome (22q11DS), a high-penetrance genetic risk factor for schizophrenia, is associated with both dopaminergic alterations and disruptions in functional connectivity (FC), yet the degree to which these separate people with 22q11DS from healthy controls and their inter-relationship remains unclear. Eighteen individuals with 22q11DS (no history of psychosis or antipsychotic use) and 22 controls underwent [18F]-DOPA PET imaging to assess striatal dopamine synthesis (indexed by Kicer values) and resting-state fMRI to examine FC. Classification performance using FC, dopamine measures, and their combination was assessed via repeated 10-fold cross-validation. Associations between Kicer, connectivity, and psychotic symptoms were evaluated using linear regression. FC alone classified 22q11DS with 68% balanced accuracy (p = 0.004), Kicer alone with 77% (p < 0.001), and combined measures with 85% balanced accuracy (p < 0.001), indicating additive value. The somatomotor and auditory networks contributed most to group discrimination. Across individuals, higher Kicer was significantly associated with more control-like connectivity profiles (p = 0.011), with significant effects in all striatal subdivisions. No association was found between FC and subclinical psychotic symptoms. This multimodal study demonstrates a significant association between striatal dopamine synthesis capacity and functional brain network architecture in 22q11DS. Higher dopamine synthesis was linked to more normative FC, potentially suggesting FC differences reflect a compensatory, rather than pathogenic role. These findings bridge genetic risk at the 22q11.2 locus with dopamine dysfunction and large-scale networks, offering novel insights into the neurobiology of 22q11DS and related neuropsychiatric risk.

INTRODUCTION: A few studies have reported that 22q11.2 del syndrome (DiGeorge syndrome - DGS) is associated with alterations in B-lymphocytes and innate immunity that predispose to infections and autoimmunity. The present study investigated the B-cell compartment, autoimmunity markers, and components of innate immunity, including NK cells, NK-specific cytotoxicity, phagocytic functions, and adhesion molecules. MATERIAL AND METHODS: Thirty-five DGS patients and twenty healthy controls were evaluated. Nephelometric, flow cytometric, ELISA and immunofluorescence techniques were used. RESULTS: There was no significant difference between the study and control groups regarding gender and age. Serum IgG, IgM levels and percentages, and antibodies against vaccine antigens were significantly lower in DGS patients. In DGS patients, 57.2% had low levels of non-switched memory B-cells, and 22.8% had low values of switched memory B-cells. Immature transitional B-cells, immature B-cells, plasmablasts, and active B-cells were significantly elevated. Autoantibodies were found positive in between 2.9% and 14.3% in the patient group. Natural killer T (NKT) cells and regulatory T cells (Tregs) were significantly decreased, whereas Fas+ active cytotoxic cells and Fas+ naive T helper cells were significantly elevated in DGS patients. NK-specific cytotoxicity was found to be higher in the patient group. CONCLUSIONS: Defects in humoral immunity, including immunoglobulin deficiencies and decreases in class-switched and nonclass-switched memory B-cell compartments, were common in DGS patients. While decreased Treg and NKT cells play a role in the increased incidence of autoimmunity, increased Fas+ cells counteract autoimmunity. Based on all these data, we would like to emphasize the importance of monitoring DGS patients for immune dysregulation.