A 22q11.2 potpourri

Wither RG, Borlot F, MacDonald A, Butcher NJ, Chow EWC, Bassett AS, Andrade DM. 22q11.2 deletion syndrome lowers seizure threshold in adult patients without epilepsy. Epilepsia. 2017 Apr 27. doi: 10.1111/epi.13748. [Epub ahead of print]

Abstract

OBJECTIVE:

Previous studies examining seizures in patients with 22q11.2 deletion syndrome (22q11.2DS) have focused primarily on children and adolescents. In this study we investigated the prevalence and characteristics of seizures and epilepsy in an adult 22q11.2DS population.

METHODS:

The medical records of 202 adult patients with 22q11.2DS were retrospectively reviewed for documentation of seizures, electroencephalography (EEG) reports, and magnetic resonance imaging (MRI) findings. Epilepsy status was assigned in accordance with 2010 International League Against Epilepsy Classification.

RESULTS:

Of 202 patients, 32 (15.8%) had a documented history of seizure. Of these 32, 23 (71.8%) had acute symptomatic seizures, usually associated with hypocalcemia and/or antipsychotic or antidepressant use. Nine patients (9/32, 28%; 9/202, 4%) met diagnostic criteria for epilepsy. Two patients had genetic generalized epilepsy; two patients had focal seizures of unknown etiology; two had epilepsy due to malformations of cortical development; in two the epilepsy was due to acquired structural changes; and in one patient the epilepsy could not be further classified.

SIGNIFICANCE:

Similarly to children, the prevalence of epilepsy and acute symptomatic seizures in adults with 22q11.2DS is higher than in the general population. Hypocalcemia continues to be a risk factor for adults, but differently from kids, the main cause of seizures in adults with 22q11.2DS is exposure to antipsychotics and antidepressants. Further prospective studies are warranted to investigate how 22q11.2 microdeletion leads to an overall decreased seizure threshold. 

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Researchers aimed to examine the prevalence and characteristics of seizures and epilepsy in an adult 22q11.2DS population. In adults with 22q11.2DS, the prevalence of epilepsy and acute symptomatic seizures is higher, similarly to children than in the general population. For adults, hypocalcemia continues to be a risk factor, but differently, from kids, in adults with 22q11.2DS the main cause of seizures is exposure to antipsychotics and antidepressants.

Methods

The researchers retrospectively reviewed the medical records of 202 adult patients with 22q11.2DS for documentation of seizures, electroencephalography (EEG) reports, and magnetic resonance imaging (MRI) findings.

They assigned epilepsy status in accordance with 2010 International League Against Epilepsy 

Classification.

Results

In this study, 32 patients (15.8%) had a documented history of seizure, out of 202 patients.

23 (71.8%) had acute symptomatic seizures, usually associated with hypocalcemia and/or antipsychotic or antidepressant use among these 32.

For epilepsy, 9 patients (9/32, 28%; 9/202, 4%) met diagnostic criteria.

As per the outcomes, 2 patients had genetic generalized epilepsy; 2 patients had focal seizures of unknown etiology; 2 had epilepsy due to malformations of cortical development; in 2 the epilepsy was due to acquired structural changes; and in 1 patient the epilepsy could not be further classified.

https://www.mdlinx.com/neurology/medical-news-article/2017/04/28/seizure-epilepsy-22q11-2-deletion-syndrome/7152998/?category=latest&page_id=2

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Suksawat Y, Sathienkijkanchai A, Veskitkul J, Jirapongsananuruk O, Visitsunthorn N, Vichyanond P, Pacharn P. Resolution of Primary Immune Defect in 22q11.2 Deletion Syndrome. J Clin Immunol. 2017 Apr 20. doi:10.1007/s10875-017-0394-6. [Epub ahead of print]

Abstract

PURPOSE:

Patients with 22q11.2 deletion syndrome have a variable decrease in immunological parameters, especially regarding T cell counts. The aim of this study was to investigate immunological change over time and factors associated with immunological recovery among patients with 22q11.2 deletion syndrome.

METHODS:

Patients with 22q11.2 deletion syndrome diagnosed by fluorescence in situ hybridization (FISH) were studied. Immunological parameters were evaluated every 6 months until patients returned to normal. Infection and vaccination histories were recorded and analyzed, and Kaplan-Meier survival curves were plotted to describe resolution of immunodeficiency.

RESULTS:

Forty-nine patients with an age range of 4 to 222 months were included. Twenty-five (51%) patients were female. In hypocalcemia, the odds ratio for CD4 lymphopenia was 17.03 (95%CI 1.82-159.23; p value = 0.01). Thirty patients (61.2%) exhibited decreased CD4+ T cell numbers, which returned to normal level in 18 (60%) patients. Median age of CD4+ T cell resolution was 2.5 years. T cell functions were abnormal in three patients. T cell functions returned to normal in all patients at a median age of 1.1 years. Six patients (13.5%) had abnormal serum immunoglobulin levels, with levels improving in four patients at 1.4 years of age. The most common infection was pneumonia (69.4%). BCG vaccination was administered in 47 of 49 patients at birth. Among 32 patients who had T cell defect, one patient developed BCGitis and one developed disseminated BCG.

CONCLUSION:

Immunodeficiencies identified among patients with 22q11.2 deletion syndrome were T cell defect (65.3%) and decreased immunoglobulin levels (12.2%). Median age of CD4 resolution was 2.5 years.

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Maggadottir SM, Sullivan KE. The diverse clinical features of chromosome 22q11.2 deletion syndrome (DiGeorge syndrome). J Allergy Clin Immunol Pract. 2013 Nov-Dec;1(6):589-94.

Abstract

A 2-year-old boy with chromosome 22q11.2 deletion syndrome was referred for recurrent sinopulmonary infections. He was diagnosed shortly after birth by a fluorescence in situ hybridization test that was performed due to interrupted aortic arch type B. He had no hypocalcemia, and his recovery from cardiac repair was uneventful. He had difficulty feeding and gained weight slowly, but, otherwise, there were no concerns during his first year of life. At 15 months of age, he began to develop significant otitis media and bronchitis. He was hospitalized once for pneumonia at 18 months of age and has never been off antibiotics for more than 1 week since then. He has not had any previous immunologic evaluation. Recurrent sinopulmonary infections in a child with chromosome 22q11.2 deletion syndrome can have the same etiologies as in any other child. Atopy, anatomic issues, cystic fibrosis, and new environmental exposures could be considered in this setting. Early childhood can be problematic for patients with chromosome 22q11.2 deletion syndrome due to unfavorable drainage of the middle ear and sinuses. Atopy occurs at a higher frequency in 22q11.2 deletion syndrome, and these children also have a higher rate of gastroesophageal reflux and aspiration than the general population. As would be appropriate for any child who presents with recurrent infections at 2 years of age, an immunologic evaluation should be performed. In this review, we will highlight recent findings and new data on the management of children and adults with chromosome 22q11.2 deletion syndrome.

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McDonald-McGinn DM, Sullivan KE, Marino B, Philip N, Swillen A, Vorstman JA, Zackai EH, Emanuel BS, Vermeesch JR, Morrow BE, Scambler PJ, Bassett AS. 22q11.2 deletion syndrome. Nat Rev Dis Primers. 2015 Nov 19;1:15071.

Abstract

22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion disorder, estimated to result mainly from de novo non-homologous meiotic recombination events occurring in approximately 1 in every 1,000 fetuses. The first description in the English language of the constellation of findings now known to be due to this chromosomal difference was made in the 1960s in children with DiGeorge syndrome, who presented with the clinical triad of immunodeficiency, hypoparathyroidism and congenital heart disease. The syndrome is now known to have a heterogeneous presentation that includes multiple additional congenital anomalies and later-onset conditions, such as palatal, gastrointestinal and renal abnormalities, autoimmune disease, variable cognitive delays, behavioural phenotypes and psychiatric illness - all far extending the original description of DiGeorge syndrome. Management requires a multidisciplinary approach involving paediatrics, general medicine, surgery, psychiatry, psychology, interventional therapies (physical, occupational, speech, language and behavioural) and genetic counselling. Although common, lack of recognition of the condition and/or lack of familiarity with genetic testing methods, together with the wide variability of clinical presentation, delays diagnosis. Early diagnosis, preferably prenatally or neonatally, could improve outcomes, thus stressing the importance of universal screening. Equally important, 22q11.2DS has become a model for understanding rare and frequent congenital anomalies, medical conditions, psychiatric and developmental disorders, and may provide a platform to better understand these disorders while affording opportunities for translational strategies across the lifespan for both patients with 22q11.2DS and those with these associated features in the general population.