Comorbid Medical Issues in X-Linked Ichthyosis.
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ABSTRACT:
SUBMITTER: Brcic L
PROVIDER: S-EPMC8938907 | biostudies-literature | 2022 May
REPOSITORIES: biostudies-literature
Publications
Comorbid Medical Issues in X-Linked Ichthyosis.
Brcic Lucija L Wren Georgina H GH Underwood Jack F G JFG Kirov George G Davies William W
JID innovations : skin science from molecules to population health 20220217 3
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Project description:BackgroundX-linked ichthyosis (XLI) is an uncommon dermatological condition resulting from a deficiency of the enzyme steroid sulfatase (STS), often caused by X-linked deletions spanning STS. Some medical comorbidities have been identified in XLI cases, but small samples of relatively young patients has limited this. STS is highly expressed in subcortical brain structures, and males with XLI and female deletion carriers appear at increased risk of developmental/mood disorders and associated traits; the neurocognitive basis of these findings has not been examined.MethodsUsing the UK Biobank resource, comprising participants aged 40-69 years recruited from the general UK population, we compared multiple medical/neurobehavioural phenotypes in males (n=86) and females (n=312) carrying genetic deletions spanning STS (0.8-2.5 Mb) (cases) to male (n=190 577) and female (n=227 862) non-carrier controls.ResultsWe identified an elevated rate of atrial fibrillation/flutter in male deletion carriers (10.5% vs 2.7% in male controls, Benjamini-Hochberg corrected p=0.009), and increased rates of mental distress (p=0.003), irritability (p<0.001) and depressive-anxiety traits (p<0.05) in male deletion carriers relative to male controls completing the Mental Health Questionnaire. While academic attainment was unaffected, male and female deletion carriers exhibited impaired performance on the Fluid Intelligence Test (Cohen's d≤0.05, corrected p<0.1). Neuroanatomical analysis in female deletion carriers indicated reduced right putamen and left nucleus accumbens volumes (Cohen's d≤0.26, corrected p<0.1).ConclusionAdult males with XLI disease-causing deletions are apparently at increased risk of cardiac arrhythmias and self-reported mood problems; altered basal ganglia structure may underlie altered function and XLI-associated psychiatric/behavioural phenotypes. These results provide information for genetic counselling of deletion-carrying individuals and reinforce the need for multidisciplinary medical care.
| S-EPMC7525778 | biostudies-literature
Project description:BackgroundHigh rates of adverse mood/neurodevelopmental traits are seen in multiple dermatological conditions, and can significantly affect patient quality of life. Understanding the sex-specific nature, magnitude, impact and basis of such traits in lesser-studied conditions like ichthyosis, is important for developing effective interventions.AimTo quantify and compare relevant psychological traits in men with X-linked ichthyosis (XLI, n = 54) or in XLI carrier women (n = 83) and in patients with ichthyosis vulgaris (IV, men n = 23, women n = 59) or psoriasis (men n = 30, women n = 122), and to identify factors self-reported to contribute most towards depressive, anxious and irritable phenotypes.MethodsParticipants recruited via relevant charities or social media completed an online survey of established questionnaires. Data were analysed by sex and skin condition, and compared with general population data.ResultsCompared with the general population, there was a higher rate of lifetime prevalence of mood disorder diagnoses across all groups and of neurodevelopmental disorder diagnoses in the XLI groups. The groups exhibited similarly significant elevations in recent mood symptoms (Cohen d statistic 0.95-1.28, P < 0.001) and neurodevelopmental traits (d = 0.31-0.91, P < 0.05) compared with general population controls, and self-reported moderate effects on quality of life and stigmatization. There were strong positive associations between neurodevelopmental traits and recent mood symptoms (r > 0.47, P < 0.01), and between feelings of stigmatization and quality of life, particularly in men. Numerous factors were identified as contributing significantly to mood symptoms in a condition or sex-specific, or condition or sex-independent, manner.ConclusionWe found that individuals with XLI, IV or psoriasis show higher levels of mood disorder diagnoses and symptoms than matched general population controls, and that the prevalence and severity of these is similar across conditions. We also identified a number of factors potentially conferring either general or condition-specific risk of adverse mood symptoms in the three skin conditions, which could be targeted clinically and/or through education programmes. In clinical practice, recognizing mood/neurodevelopmental problems in ichthyosis and psoriasis, and addressing the predisposing factors identified by this study should benefit the mental health of affected individuals.
| S-EPMC9314151 | biostudies-literature
Project description:ObjectiveShortened life expectancy of people with mental disorders has been attributed to medical comorbidities, yet these conditions remain under-recognized and under-treated. This study characterizes the medical demands placed on inpatient psychiatric units to help guide medical assessment and management practices in these settings.MethodsMedicaid claims records and clinician data were linked with hospital and regional data for individuals with a principal diagnosis of any mental disorder admitted to psychiatric inpatient units in New York State from 2012 to 2013. A modified Elixhauser Comorbidity Index (ECI) score was calculated for each unique individual (n = 14,458). Adjusted odds ratios (AORs) of having a medical comorbidity were calculated using logistic regression analyses.Results74.9% of psychiatric inpatients had at least one medical comorbidity, including 57.5% of people ages 18-24. Higher rates of medical comorbidity were associated with older age, female gender, non-schizophrenia diagnoses, and engagement in care prior to hospitalization. Patients with medical comorbidities had lower odds (AOR 0.54; 99% CI 0.35-0.83) of being treated in hospitals with 100 or more total beds compared to smaller hospitals.ConclusionsA high prevalence of common medical diagnoses among psychiatric inpatients underscores the importance of adequate detection and medical treatment of medical comorbidities in psychiatric inpatient settings.
| S-EPMC8684817 | biostudies-literature
Project description:Recessive X-linked ichthyosis (RXLI), a genetic disorder caused by deletion or point mutations of the steroid sulfatase (STS) gene, is the second most common form of ichthyosis. It is a disorder of keratinocyte cholesterol sulfate retention and the mechanism of extracutaneous phenotypes such as corneal opacities and attention deficit hyperactivity disorder are poorly understood. To understand the pathomechanisms of RXLI, the transcriptome of differentiated primary keratinocytes with STS knockdown was sequenced. The results were validated in a stable knockdown model of STS, to confirm STS specificity, and in RXLI skin. The results show that there was significantly reduced expression of genes related to epidermal differentiation and lipid metabolism, including ceramide and sphingolipid synthesis. In addition, there was significant downregulation of aldehyde dehydrogenase family members and the oxytocin receptor which have been linked to corneal transparency and behavioural disorders respectively, both of which are extracutaneous phenotypes of RXLI. These data provide a greater understanding of the causative mechanisms of RXLI's cutaneous phenotype, and show that the keratinocyte transcriptome and lipidomics can give novel insights into the phenotype of patients with RXLI.
| S-EPMC10285781 | biostudies-literature
Project description: Not available
| S-EPMC4834452 | biostudies-literature
Project description:ObjectiveRecessive X-linked ichthyosis (RXLI) caused by deficiency of the steroid sulfatase gene (STS) has a reported prevalence of 1/2000 to 1/6000. The present study aimed to characterize the phenotypes and genotypes of two Chinese families with RXLI.MethodsThe patients were referred to the Family Planning Research Institute of Hunan Province for genetic counseling. Their skin phenotypes were photographed, and venous blood was drawn and used for chromosomal microarray analysis (CMA).ResultsThe skin phenotype of the proband from the first family was characterized by generalized skin dryness and scaling, with noticeable dark brown, polygonal scales on his trunk and extensor surfaces of his extremities. The proband from the second family had an atypical phenotype showing mild skin dryness over his entire body, slight scaling on his abdomen, and small skin fissures on his arms and legs. No mental disability or developmental anomaly was noted in either proband. CMA revealed that both probands carried a 1.4-Mb deletion on chromosome Xp22.31 involving four Online Mendelian Inheritance in Man-listed genes including STS.ConclusionsOur findings add knowledge to the genotype and phenotype spectrum of RXLI, which may be helpful in genetic counseling and prenatal diagnosis.
| S-EPMC7545777 | biostudies-literature
Project description:Recessive X-linked ichthyosis (RXLI), a genetic disorder caused by deletion or point mutations of the steroid sulfatase (STS) gene, is the second most common form of ichthyosis. It is a disorder of keratinocyte cholesterol sulphate retention and the mechanism of extracutaneous phenotypes such as corneal opacities and attention deficit hyperactivity disorder are poorly understood. To understand the pathomechanisms of RXLI, the transcriptome of differentiated primary keratinocytes with STS knockdown was sequenced. The results were validated at the protein level in a stable knockdown model of STS, to confirm STS specificity, and in RXLI skin. The results show that there was significantly reduced expression of genes related to epidermal differentiation and lipid metabolism, including ceramide and sphingolipid synthesis. In addition, there was significant downregulation of aldehyde dehydrogenase family members and the oxytocin receptor which have been linked to corneal transparency and behavioural disorders respectively, both of which are extracutaneous phenotypes of RXLI. These data provide a greater understanding of the causative mechanisms of RXLI’s cutaneous phenotype, and show that the keratinocyte transcriptome and lipidomics can give novel insights into the phenotype of patients with RXLI.
2023-05-30 | GSE232622 | GEO
Project description:X-linked ichthyosis is a relatively common syndromic form of ichthyosis most often due to deletions in the gene encoding the microsomal enzyme, steroid sulfatase, located on the short area of the X chromosome. Syndromic features are mild or unapparent unless contiguous genes are affected. In normal epidermis, cholesterol sulfate is generated by cholesterol sulfotransferase (SULT2B1b), but desulfated in the outer epidermis, together forming a 'cholesterol sulfate cycle' that potently regulates epidermal differentiation, barrier function and desquamation. In XLI, cholesterol sulfate levels my exceed 10% of total lipid mass (≈1% of total weight). Multiple cellular and biochemical processes contribute to the pathogenesis of the barrier abnormality and scaling phenotype in XLI. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.
| S-EPMC3966299 | biostudies-literature
Project description:X-linked ichthyosis (XLI) is a rare X-linked dermatological condition arising from deficiency for the enzyme steroid sulfatase (STS). STS is normally expressed in the brain, and males with XLI exhibit personality differences from males in the general population, and are at increased risk of developmental and mood disorders. As the STS gene escapes X-inactivation, female carriers of XLI-associated genetic mutations have reduced STS expression/activity relative to non-carrier females, and could manifest similar behavioural phenotypes to males with XLI. Additionally, as STS activity normally increases in female tissues towards late pregnancy and into the puerperium, carrier females could theoretically present with increased rates of postpartum psychopathology. Using a worldwide online survey comprising custom-designed demographic questionnaires and multiple validated psychological questionnaires, we collected detailed self-reported information on non-postpartum and postpartum behaviour in confirmed adult (>16yrs) female carriers of genetic mutations associated with XLI (n = 94) for statistical comparison to demographically-matched previously-published normative data from female controls (seven independent studies, 98≤n≤2562), adult males with XLI (n = 58), and to newly-obtained online survey data from a general population sample of mothers from the United Kingdom and United States of America (n = 263). The pattern of results in carrier females relative to controls was remarkably similar to that previously observed in males with XLI, with evidence for increased rates of developmental and mood disorders, and elevated levels of inattention, impulsivity, autism-related traits and general psychological distress. Carrier females exhibited a significantly elevated rate of postpartum mental health conditions (notably mild depression) relative to controls which could not be accounted for by social factors. Our data confirm the psychological profile associated with XLI-associated mutations, and suggest that female carriers may be at increased risk of psychopathology, including in the postpartum period. These findings are relevant to families affected by XLI, to clinicians involved in the care of these families, and to genetic counsellors.
| S-EPMC6377116 | biostudies-literature
Project description:ImportancePremature mortality has been observed among people with mental disorders. Comorbid general medical conditions contribute substantially to this reduction in life expectancy.ObjectiveTo provide an analysis of mortality associated with comorbidity between a broad range of mental disorders and general medical conditions.Design, setting, and participantsPopulation-based cohort study of 5 946 800 individuals born in Denmark from 1900 to 2015 and residing in the country at the start of follow-up (January 1, 2000, or their date of birth, whichever occurred later).ExposuresDanish health registers were used to identify people with mental disorders and general medical conditions.Main outcomes and measuresConsidering pairs of mental disorders and general medical conditions, we calculated mortality rate ratios (MRRs) and differences in life expectancy (ie, life-years lost) to assess the association of mortality with both disorders of interest compared with the mental disorder of interest, the general medical condition of interest, and neither disorder of interest.ResultsThe study population comprised 2 961 397 males and 2 985 403 females, with a median (IQR) age of 32.0 years (7.3-52.9) at start of follow-up and 48.9 years (42.5-68.8) at the end. Based on all pairs of comorbid mental disorders and general medical conditions, the mean MRR compared with people without these conditions was 5.90 (median, 4.94; IQR, 3.80-7.30), and the mean reduction of life expectancy compared with the general population was 11.35 years (median, 11.08; range, 5.27-23.53; IQR, 8.22-13.72). The association with general medical condition comorbidity in those with mental disorders varied by general medical condition; for example, the addition of a neurological condition for each of the mental disorders was associated with a mean MRR of 1.22, whereas for cancer, the mean MRR for all mental disorders was 4.07.Conclusions and relevanceIn this study, shorter life expectancy was associated with comorbid mental disorders and general medical conditions compared with the entire population and also when compared with patients who had either mental disorders only or general medical conditions only. Prevention and early detection of comorbidities could reduce premature mortality in patients with mental disorders.
| S-EPMC8968685 | biostudies-literature