Pure direct duplication (12)(q24.1-->q24.2) in a child with Marcus Gunn phenomenon and multiple congenital anomalies

Partial trisomy of the region 12q24.1-->q24.2 is rare and usually associated with other rearrangements. We report on the clinical and cytogenetic findings in a girl with a pure de novo direct duplication dup(12)(q24.1-->q24.2). She had developmental and growth retardation, facial dysmorphism with upslanting palpebral fissures, wide downturned mouth, short neck, and Marcus Gunn phenomenon. She also had single transverse creases, hypoplasia of the corpus callosum, and cardiac malformations consisting of a bicuspid aortic valve, multiple ventricular septal defects, and kinking of the aorta. The size of the duplication was characterized by molecular cytogenetics and comparative genomic hybridization (CGH) to be 11.5 Mb in size and extended from the BAC probe RP11-256L11 loci (108.2 Mb) +/- 1 Mb to the BAC probe RP11-665J20 loci (119.7 Mb) +/- 1 Mb. No such pure 12q24 duplication was detected out of the 23 patients reported in the literature with duplications in 12q region. Comparison with these reported 12q trisomies suggests the duplication dup(12)(q24.1-->q24.2) is associated with a recognizable phenotype consisting of characteristic facial dysmorphism, growth retardation, and cardiac malformation.     

Phase-Based Treatment of a Complex Severely Mentally Ill Case Involving Complex Posttraumatic Stress Disorder and Psychosis Related to Dandy Walker Syndrome

For patients with comorbid complex posttraumatic stress disorder (PTSD) and psychotic disorder, trauma-focused therapy may be difficult to endure. Phase-based treatment including (a) stabilization, (b) trauma-focused therapy, and (c) integration of personality with recovery of connection appears to be the treatment of choice. Objective: The objective of this article is to describe and evaluate the therapeutic process of a single case from a holistic perspective. Method: We present a case report of a 47-year-old woman treated for severe complex PTSD resulting from repeated sexual and physical abuse in early childhood and moderate psychotic symptoms stemming from Dandy Walker Syndrome with hydrocephalus. Results: The patient was treated with quetiapine (600–1,000 mg) and citalopram (40 mg). Stabilization consisted of intensive psychiatric nursing care in the home and stabilizing group treatment for complex PTSD. After stabilization, the following symptom domains showed improvement: self-regulation, self-esteem, assertiveness, avoidance of social activities, and negative cognitions. However, intrusions and arousal persisted and were therefore subsequently treated with prolonged imaginary exposure that also included narrative writing assignments and a final closing ritual. This intensive multidisciplinary, phase-based approach proved effective: All symptoms of complex PTSD were in full remission. Social integration and recovery were promoted with the reduction of polypharmacy and the provision of social skills training and lifestyle training. Conclusion: The present case shows a phase-based treatment approach with multidisciplinary collaborative care to be effective for the treatment of a case of complex PTSD with comorbid psychotic disorder stemming from severe neurological impairment. Replication of this promising approach is therefore called for.     

Notable contribution of large CFTR gene rearrangements to the diagnosis of cystic fibrosis in fetuses with bowel anomalies

Grade III fetal bowel hyperechogenicity and/or loop dilatation observed at the second trimester of pregnancy can be due to several disease conditions, including cystic fibrosis (CF). Screening for frequent CF mutations is performed as a first step and, in certain situations, such as when a frequent CF mutation is found in the fetus, the increased risk of CF justifies an in-depth study of the second allele. To determine the contribution of large CFTR gene rearrangements in such cases, detected using a semiquantitative fluorescent multiplex PCR (QFM-PCR) assay, we collated data on 669 referrals related to suspicion of CF in fetuses from 1998 to 2009. Deletions were found in 5/70 cases in which QFM-PCR was applied, dele19, dele22_23, dele2_6b, dele14b_15 and dele6a_6b, of which the last three remain undescribed. In 3/5 cases, hyperechogenicity was associated with dilatation and/or gallbladder anomalies. Of the total cases of CF recognized in the subgroup of first-hand referrals, deletions represent 16.7% of CF alleles. Our study thus strengthens the need to consider large CFTR gene rearrangements in the diagnosis strategy of fetal bowel anomalies, in particular in the presence of multiple anomalies.     

Encephalomyelitis-associated antimyelin autoreactivity induced by streptococcal exotoxins

OBJECTIVE: After implicating Streptococcus pyogenes as causing acute disseminated encephalomyelitis (ADEM) in a child, we wanted to prove that in vivo activation of autoreactive T lymphocytes by superantigens of this Streptococcus contributed to the dramatic demyelination. BACKGROUND: ADEM is a demyelinating disorder of the CNS sharing many similarities with MS. Demyelination in MS is considered to be the result of an autoimmune process mediated by autoreactive T lymphocytes with specificity for myelin antigens. METHODS: Phenotypic analysis and proliferation assays on blood monocytes, as well as isolation of myelin basic protein (MBP)-reactive T-cell lines/clones; and TCR repertorium analysis by PCR-ELISA and cytokine production. RESULTS: 1) The blood T-cell receptor (TCR) repertoire was compatible with in vivo expansion induced by S. pyogenes exotoxins. 2) TCR expression analysis indicated clonal expansion of CD8+ MBP-reactive T cells, suggesting in vivo activation. MBP-reactive T cells showed crossreactivity to S. pyogenes supernatant and exotoxins. 3) Cytokine mRNA quantification of the mononuclear cells revealed a Th2-biased profile. CONCLUSION: In vivo exposure to S. pyogenes may have induced activation of pathogenic myelin reactive T cells, contributing to the dramatic inflammatory demyelination.     

Hepatitis C virus-induced hepatocellular carcinoma

Hepatitis C virus (HCV) is a leading etiology of hepatocellular carcinoma (HCC). The interaction of HCV with its human host is complex and multilayered; stemming in part from the fact that HCV is a RNA virus with no ability to integrate in the host''s genome. Direct and indirect mechanisms of HCV-induced HCC include activation of multiple host pathways such as liver fibrogenic pathways, cellular and survival pathways, interaction with the immune and metabolic systems. Host factors also play a major role in HCV-induced HCC as evidenced by genomic studies identifying polymorphisms in immune, metabolic, and growth signaling systems associated with increased risk of HCC. Despite highly effective direct-acting antiviral agents, the morbidity and incidence of liver-related complications of HCV, including HCC, is likely to persist in the near future. Clinical markers to selectively identify HCV subjects at higher risk of developing HCC have been reported however they require further validation, especially in subjects who have experienced sustained virological response. Molecular biomarkers allowing further refinement of HCC risk are starting to be implemented in clinical platforms, allowing objective stratification of risk and leading to individualized therapy and surveillance for HCV individuals. Another role for molecular biomarker-based stratification could be enrichment of HCC chemoprevention clinical trials leading to smaller sample size, shorter trial duration, and reduced costs.     

The relation between the localization of foot dermatitis and the causative allergens in shoes: a 13-year retrospective study

The purpose of this retrospective study was to test whether the initial pattern of clinical presentation of shoe dermatitis could indicate the causative allergen(s) and to estimate the odds on foot dermatitis in patients with a positive patch test versus those with a negative patch-test result. Between 1990 and 2002, 8543 patients were patch tested with the standard series (and additional allergens, if appropriate). Of them, 1168 (14%) had been referred because of foot dermatitis and 474 of these patients (5.5% of the total group) presented a positive reaction to one or more substances related to shoes. We found that 6 standard allergens in the male group and 8 standard allergens in the female group were statistically significant for the shoe dermatitis group. The data showed a relationship between the distribution pattern of the foot lesions and most of the allergens. These results have clinical applications since the gender of the patients and the localization of the foot eruptions can, indeed, indicate what allergen is involved.     

Adding sorbitan sesquioleate to the European baseline series: Necessary,reasonable, or unavoidable?

Positive reactions to fragrance mix I (FM I) are frequent in consecutively patch tested patients suspected of having allergic contact dermatitis. However, the FM I test preparations contain 5% of the emulsifier sorbitan sesquioleate (SSO), and it is well known that SSO can cause contact allergic reactions in its own right. Indeed, the available data show that some patients with contact allergy to SSO react to FM I but are not allergic to fragrances. When SSO is not tested, this situation may go unnoticed, a wrong diagnosis of fragrance allergy may be given to the patient, and unjustified advice to avoid fragrances and fragranced products will be given in such cases. To avoid such suboptimal patient care, we postulate that testing with SSO in all patch tested individuals is mandatory. As it is well known that only a minority of FM I‐reactive patients will undergo a breakdown test with the ingredients and SSO, testing with SSO in all patients can only be achieved by adding it to the European baseline series. Not testing with SSO may also result in misinterpretation of patch test reactions to Myroxylon pereirae resin and 2‐hydroxyethyl methacrylate in the baseline series, as both (may) contain SSO, and, for the same reason, of reactions to several other hapten test materials.