HIDEA syndrome: A new case report highlighting similarities with ROHHAD syndrome.

Context: ROHHAD syndrome presents a significant resemblance to HIDEA syndrome. The latter is caused by biallelic loss-of-function variants in the P4HTM gene and encompasses hypotonia, intellectual disabilities, eye abnormalities, hypoventilation, and dysautonomia. We report the first patient identified with HIDEA syndrome from our ROHHAD cohort. Clinical case: Our patient was a 21-month-old girl who had a history of severe respiratory infections requiring intensive care, hypotonia, abnormal eye movements, and rapid weight gain. Polysomnography identified severe central hypoventilation. During her follow-up, a significant psychomotor delay and the absence of language were gradually observed. The prolactin levels were initially increased. Hypothermia was reported at 4 years. Exome sequencing identified a new homozygous truncating P4HTM variant. Discussion: Our patient met the diagnosis criteria for ROHHAD, which included rapid weight gain, central hypoventilation appearing after 1.5 years of age, hyperprolactinemia suggesting hypothalamic dysfunction, and autonomic dysfunction manifesting as strabismus and hypothermia. However, she also presented with severe neurodevelopmental delay, which is not a classic feature of ROHHAD syndrome. HIDEA syndrome presents similarities with ROHHAD, including hypoventilation, obesity, and dysautonomia. To date, only 14% of endocrinological disturbances have been reported in HIDEA patients. Better delineation of both syndromes is required to investigate the eventual involvement of P4HTM, a regulator of calcium dynamics and gliotransmission, in ROHHAD patients. Conclusion: In the case of clinical evidence of ROHHAD in a child with abnormal neurological development or eye abnormalities, we suggest that the P4HTM gene be systematically interrogated in addition to the analysis of the PHOX2B gene. A better delineation of the natural history of HIDEA is required to allow further comparisons between features of HIDEA and ROHHAD. The clinical similarities could potentially orient some molecular hypotheses in the field of ROHHAD research.

[A Familial Non Medullary Thyroid Carcinoma (FNMTC) : a clinical and genetic update]. / Cancer thyroïdien familial non médullaire: actualités cliniques et génétiques.

The syndrome of Familial Non Medullary Thyroid Carcinoma (FNMTC) includes two or more patients with an isolated non-medullary thyroid cancer (papillary, follicular, anaplastic) within the same family. To diagnose FNMTC, the clinician must exclude a syndromic presentation such as the syndromes of Cowden, Gardner or Werner, and the Carney Complex. Up to now, a hundred families with FNMTC have been genetically studied, including forms with (Ch19p13.2) or without oxyphilia (Ch2q21), in association with a multinodular goiter (Ch14q32), or with a renal cancer (Ch1q21). Several candidate genes of susceptibility have been proposed: SRGAP1, NKX2-1, FOXE1 and HABP2. So far, it is considered that familial cases represent less than 5 % of thyroid cancers. Although rare, these cases represent a unique opportunity to improve our understanding of thyroid cancer. The identification of candidate genes will enrich our knowledge of thyroid cancer pathophysiology. Based on the literature and our experience of the follow-up of eight families with FNMTC, we discuss epidemiological, clinical, pathological and genetic aspects of FNMTC with a view to improve the diagnosis and treatment of this disease.

Le syndrome de «Familial Non Medullary Thyroid Carcinoma¼ (FNMTC) suppose l'existence, au sein d'une même famille, de deux ou plusieurs patients avec un cancer thyroïdien non médullaire isolé (papillaire, folliculaire, anaplasique). Le diagnostic de FNMTC est retenu après exclusion d'une présentation syndromique comme celle liée aux syndromes de Cowden, Gardner, ou Werner et au Complexe de Carney. Une centaine de familles de FNMTC ont été bien caractérisées sur le plan génétique, incluant des formes papillaires avec (Ch19p13.2) ou sans oxyphilie (Ch2q21, 6q22), en association avec un goitre multinodulaire (14q32), ou avec un cancer rénal (Ch1q21). Plusieurs gènes de susceptibilité ont été proposés : SRGAP1, NKX2-1, FOXE1, et HABP2. On estime que les cas familiaux représentent moins de 5 % des cancers thyroïdiens. Bien que minoritaires, ils représentent une occasion exceptionnelle d'approfondir notre compréhension de la tumorigenèse du cancer thyroïdien et d'identifier des gènes candidats pouvant participer à leur physiopathologie. A partir d'une revue de la littérature et de notre expérience sur le suivi de huit familles avec FNMTC, nous discutons des aspects épidémiologiques, cliniques, pathologiques et génétiques permettant d'aboutir à un meilleur diagnostic et à une prise en charge de ce syndrome oncologique.

Thermodynamics of intragenic nucleosome ordering.

The nucleosome ordering observed in vivo along yeast genes is described by a thermodynamical model of nonuniform fluid of 1D hard rods confined by two excluding energy barriers at gene extremities. For interbarrier distances L less than or approximately equal to 1.5 kbp, nucleosomes equilibrate into a crystal-like configuration with a nucleosome repeat length (NRL) L/n approximately 165 bp, where n is the number of regularly positioned nucleosomes. We also observe "bistable" genes with a fuzzy chromatin resulting from a statistical mixing of two crystal states, one with an expanded chromatin (NRL approximately L/n) and the other with a compact one (NRL approximately L/(n+1)). By means of single nucleosome switching, bistable genes may drastically alter their expression level as suggested by their higher transcriptional plasticity. These results enlighten the role of the intragenic chromatin on gene expression regulation.

Sensitivity of indirect immunofluorescence and ELISA in detecting intercellular antibodies in endemic pemphigus foliaceus (Fogo Selvagem).

BACKGROUND: Since 1967 dermatology has used the classic technique of indirect immunofluorescence (IFI) for the detection of autoantibodies against antigens of the skin in diseased people with endemic pemphigus foliaceus. Thirty years later enzyme-linked immunosorbent assays--ELISA (rDsg1 and rDsg3) appeared as a viable option. A group of highly recognized researchers have concluded that ELISA is a simple, sensitive and highly specific method, allowing for diagnostic differentiation between pemphigus vulgaris (PV) and endemic pemphigus foliaceus (EPF). Scientific literature certifies that both ELISA and IIF bear high sensitivity in spite of the fact that a direct comparison between the ELISA and IIF tests has never been performed. OBJECTIVES: This study was conducted to compare the sensitivity of these tests in detecting antibodies in the EPF. MATERIAL AND METHODS: Thirty-two serum samples were collected from patients with EPF. The control serum of 15 healthy individuals was tested to detect the presence of antibodies of EPF by indirect immunofluorescence and ELISA (rDsg1 and rDsg3). The IIF was performed, taking human skin as a substrate. RESULTS: Antibodies in patients with EPF were detected more commonly by the ELISA (rDsg1) (91%) compared with IIF (81%). CONCLUSIONS: The ELISA (rDsg1) is slightly more sensitive than IIF in detecting antibodies related to EPV. However, according to our results, we do not currently possess a test with 100% accuracy in differentiating EPF from PV. Although previous studies have associated Dsg3 with PV, the tests performed during this study showed that 12% (4/32) of patients with EPF (cutaneous diseases only) also had Dsg3 antibodies.