EPG5-Related Vici Syndrome: A Primary Defect of Autophagic Regulation with an Emerging Phenotype Overlapping with Mitochondrial Disorders.

Vici syndrome is a rare, under-recognised, relentlessly progressive congenital multisystem disorder characterised by five principal features of callosal agenesis, cataracts, cardiomyopathy, combined immunodeficiency and oculocutaneous hypopigmentation. In addition, three equally consistent features (profound developmental delay, progressive failure to thrive and acquired microcephaly) are highly supportive of the diagnosis. Since its recognition as a distinct entity in 1988, an extended phenotype with sensorineural hearing loss, skeletal myopathy and variable involvement of virtually any organ system, including the lungs, thyroid, liver and kidneys, have been described.Autosomal recessive mutations in EPG5 encoding ectopic P-granules autophagy protein 5 (EPG5), a key autophagy regulator implicated in the formation of autolysosomes, were identified as the genetic cause of Vici syndrome. The eight key features outlined above are highly predictive of EPG5 involvement, with pathogenic EPG5 mutations identified in >90% of cases where six or more of these features are present. The manifestation of all eight features has a specificity of 97% and sensitivity of 89% for EPG5-related Vici syndrome. Nevertheless, substantial clinical overlap exists with other multisystem disorders, in particular congenital disorders of glycosylation and mitochondrial disorders. Clinical and pathological findings suggest Vici syndrome as a paradigm of congenital disorders of autophagy, a novel group of inherited neurometabolic conditions linking neurodevelopment and neurodegeneration due to primary autophagy defects.Here we describe the diagnostic odyssey in a 4-year-old boy whose clinical presentation with multisystem manifestations including skeletal myopathy mimicked a mitochondrial disorder. A genetic diagnosis of Vici syndrome was made through whole genome sequencing which identified compound heterozygous variants in EPG5. We also review the myopathic presentation and morphological characterisation of previously reported cases.

Panic disorder as a risk factor for post-partum depression: Results from the Perinatal Depression-Research & Screening Unit (PND-ReScU) study.

BACKGROUND: Although the role of anxiety disorders on the development of Post-partum Depression (PPD) have already been studied in literature, that of individual anxiety disorders has not received specific attention. The aim of this study is to investigate the role of Panic Disorder (PD) and family history for PD as risk factors for PPD. METHODS: Six hundred women were recruited in a prospective, observational study at the 3rd month of pregnancy and followed up until the 6th month after delivery. At baseline, risk factors for PPD, Axis-I disorders and family history for psychiatric disorders were assessed. We investigated minor and major depression (mMD) occurred at 1st, 3rd and 6th months post-partum. Logistic regression models were used to estimate the association between PD, family history for PD and PPD. RESULTS: Forty women had mMD in the post-partum. PD during pregnancy (RR=4.25; 95%CI:1.48-12.19), a history of PD (RR 2.47; 95%CI:1.11-5.49) and family history for PD (RR=2.1; 95%CI:1.06-4.4) predicted PPD after adjusting for lifetime depression and risk factors for PPD. LIMITATIONS: The response rate is moderately low, but it is similar to other studies. The drop out rate is slightly high, however the 600 women who completed the 6th month follow-up did not differ from the presence of PD at baseline. CONCLUSIONS: PD is an independent risk factor for PPD, underscoring need to assess PD symptoms during pregnancy. Furthermore, PD represents an important risk factor for the development of PPD and should be routinely screened in order to develop specific preventive interventions.

Risk factors for postpartum depression: the role of the Postpartum Depression Predictors Inventory-Revised (PDPI-R). Results from the Perinatal Depression-Research & Screening Unit (PNDReScU) study.

The aims of this study were to identify the frequency of the risk factors for postpartum depression (PPD) listed in the Postpartum Depression Predictors Inventory-Revised (PDPI-R) during pregnancy and 1 month after delivery and to determine the predictive validity of the PDPI-R. The study used a prospective cohort design. Women completed the PDPI-R at the 3rd and the 8th months of pregnancy and at the 1st month after childbirth. Women were prospectively followed across three different time points during the postpartum using Structured Clinical Interview for DSM-IV Disorders to determine the presence of major or minor depression. The prenatal version of the PDPI-R administered at two different time points during pregnancy predicted accurately 72.6% and 78.2% of PPD and the full version administered at the 1st month after delivery predicted 83.4% of PPD. The cutoffs identified were 3.5 for the prenatal version and 5.5 for the full version. The PDPI-R is a useful and a valid screening tool for PPD.

Early progressive encephalopathy in boys and MECP2 mutations.

MECP2 mutations mainly occur in females with Rett syndrome. Mutations have been described in 11 boys with progressive encephalopathy: seven of nine with affected sisters and two de novo. The authors report four de novo occurrences: three pathogenic and one potentially pathogenic. Common features include failure to thrive, respiratory insufficiency, microcephaly, and abnormal motor control. MECP2 mutations should be assessed in boys with progressive encephalopathy and one or more of respiratory insufficiency, abnormal movements or tone, and intractable seizures.

Soluble N-ethylmaleimide-sensitive-factor attachment protein and N-ethylmaleimide-insensitive factors are required for Ca2+-stimulated exocytosis of insulin.

Ca2+ stimulates exocytosis in permeabilized insulin-secreting cells. To investigate the putative cytosolic components involved in the Ca2+ response, HIT-T15 cells (a pancreatic B-cell line) were permeabilized with streptolysin-O, a procedure that allows rapid exchange of soluble components including macromolecules. We found that in this cell preparation the secretory response to Ca2+ but not to guanosine 5'-[gamma-thio]triphosphate was lost as a function of time and could be restored by rat brain cytosol in a concentration-dependent manner. Reconstitutive activity of rat brain cytosol was found in a high-molecular-mass heat-labile partially N-ethylmaleimide(NEM)-sensitive fraction. The NEM-sensitive factor (NSF) and the soluble NSF attachment protein (alpha-SNAP) were found to be expressed in HIT-T15 cells and largely lost (about 30% remaining) from porated cells. Recombinant alpha-SNAP partially reconstituted the Ca2+ response when added to the permeabilized cells. Moreover, alpha-SNAP restored the effect of NEM-treated cytosol to the level observed for untreated cytosol. In contrast, NSF was ineffective when preincubated alone or with NEM-treated cytosol. Our results indicate that both alpha-SNAP and NEM-insensitive cytosolic factors are involved in Ca2+-mediated exocytosis from endocrine HIT-T15 cells.

[Primary lymphoma of the kidney. Description of a case and brief review of the literature]. / Il linfoma primitivo del rene. Descrizione di un caso e breve revisione della letteratura.

Stage IV disseminated non-Hodgkin lymphomas show kidney involvement with frequency; on the contrary, primary kidney lymphoma, as the sole presenting feature, is a very rare disease. Non-Hodgkin histological pattern, atypical symptoms, marked discrepancy between parenchymal involvement and impairment of renal function are the main features of this tumor. A case-report of a primary kidney non-Hodgkin lymphoma will be described; a short review of literature on this subject will be discussed.

Psychotic symptom patterns and the diagnosis of schizophrenia.

In comparing 101 psychotic patients subtyped by DSM-III criteria into paranoia, schizophrenia, schizoaffective, and affective disorders, we failed to distinguish them on the basis of delusional and hallucinatory experiences. These 'productive', 'positive' or 'irritative' symptoms--which the literature tends to link with temporolimbic dysfunction--did not appear specifically linked to schizophrenia. By contrast, 'negative' or 'deficit' symptoms--which the literature tends to relate to frontal lobe dysfunction--appeared more specific--especially for the disorganized subtype of schizophrenia. Although these data tend to support Bleulerian over Schneiderian conceptualization of schizophrenia, the heterogeneity of neuropsychological deficits implied in the negative symptom complexes limits the nosologic utility of the rubric of schizophrenia so defined.

[Lymphoma of the prostate: case reports and subject review]. / Il linfoma della prostata: contributo clinico e revisione dell'argomento.

Malignant lymphomas involving the prostate are rare whether as primary lymphoma or as secondary to generalized disease. Middle age, histotype prevalently non Hodgkin, intermediate and high grade of malignancy, symptoms of bladder outflow obstruction, diagnosis generally made after histological examination, severe prognosis are the most important features that result from literature review. The evaluation of therapeutic treatments is difficult as most reports do not include a sufficient number of cases. The Authors presenting two cases of lymphoma of the prostate point out the usefulness of radiotherapy since the prostate is usually a bulky seat of disease and suggest the combination with multiple drug chemotherapy for intermediate and high grade of malignancy and in advanced stages. The authors suggest that prognosis depends on histotype rather than on prostatic involvement of disease.

[Normally functioning goiter: reflections on the clinical course. A 30-year follow up]. / Gozzo normofunzionante: considerazioni sul decorso clinico. Trent'anni di osservazione.

Among the 984 patients suffering from thyroid pathology observed in our Department between 1956 and 1964, we took into consideration the 184 patients who having been diagnosed as having a normally functioning goitre, were not given any treatment. We chose 88 patients living in our region, under 60 years old: 55 of these were included in our study. The long period involved--30 years--allowed us to check the natural course of this pathology, which was shown to be totally benign as well as frequent, and unconnected with other pathologies. Only in one case, at a distance of 20 years, did a neoplasia arise. The evaluation of the results justifies a decision of non-intervention, while recognising the paramount importance of a correct diagnosis, already possible with the diagnostic instruments then available.