Imatinib is a promising candidate for the treatment of fibrotic diseases. This retrospective study evaluated the use of imatinib for the treatment of refractory sclerotic chronic graft-versus-host ...disease in 14 patients with different hematologic malignancies. Imatinib was started at a median of 44 months after transplantation (range, 16-119 months after transplantation) and was administered for a median of 5.9 months from time of initiation (range, 2.1-74 months from time of initiation). With a median overall follow-up of 11.6 months from time of initiation (range, 4.1-74 months from time of initiation) of imatinib, 4 patients (29%) had to stop imatinib because of drug intolerance. All other adverse reactions were of mild-to-moderate grade and could be managed symptomatically. Overall, 7 patients responded to imatinib (50%; 95% confidence interval, 24%-76%) with 4 patients improving their Rodman score more than or equal to 90%. In addition, imatinib therapy allowed for a significant reduction of corticosteroid dosage. Despite its limited size, this cohort suggests some beneficial activity of imatinib in sclerotic chronic graft-versus-host disease, warranting further prospective investigations.
Hypomelanosis of Ito (HI) is a skin marker of somatic mosaicism. Mosaic MTOR pathogenic variants have been reported in HI with brain overgrowth. We sought to delineate further the pigmentary skin ...phenotype and clinical spectrum of neurodevelopmental manifestations of MTOR-related HI.
From two cohorts totaling 71 patients with pigmentary mosaicism, we identified 14 patients with Blaschko-linear and one with flag-like pigmentation abnormalities, psychomotor impairment or seizures, and a postzygotic MTOR variant in skin. Patient records, including brain magnetic resonance image (MRI) were reviewed. Immunostaining (n = 3) for melanocyte markers and ultrastructural studies (n = 2) were performed on skin biopsies.
MTOR variants were present in skin, but absent from blood in half of cases. In a patient (p.Glu2419Lys variant), phosphorylation of p70S6K was constitutively increased. In hypopigmented skin of two patients, we found a decrease in stage 4 melanosomes in melanocytes and keratinocytes. Most patients (80%) had macrocephaly or (hemi)megalencephaly on MRI.
MTOR-related HI is a recognizable neurocutaneous phenotype of patterned dyspigmentation, epilepsy, intellectual deficiency, and brain overgrowth, and a distinct subtype of hypomelanosis related to somatic mosaicism. Hypopigmentation may be due to a defect in melanogenesis, through mTORC1 activation, similar to hypochromic patches in tuberous sclerosis complex.
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The aim of this study was to define the skin patterns at high risk for upper airway infantile haemangioma. A retrospective multicentre French observational study was conducted between January 2006 ...and January 2015 and all confirmed airway haemangioma were included. Thirty-eight patients with airway haemangioma from 9 centres were included. Thirty-one patients had a cutaneous or mucosal haemangioma: 21 with a location considered at high risk for airway haemangioma (large segmental mandibular haemangioma), 4 with a very mild facial involvement (lower lip or S1 (frontotemporal segment according to Haggstrom and Frieden)) and 6 with either lesions of the neck or body, or association of both. We report here the largest cohort of airway haemangioma. A third of patients do not completely fit with the definition of the high-risk area of airway haemangioma. Segmental lower lip and neck involvement also seem to be very suggestive areas. Clinicians must be able to recognize these areas.
Telangiectasia-ectodermal dysplasia-brachydactyly-cardiac anomaly (TEBC) syndrome is a rare autosomal dominant condition, recently linked to the protein kinase D1 (PRKD1) gene. The phenotype of TEBC ...remains incomplete at this point. Our aim is to improve the characterization of the clinical and molecular aspects of the TEBC syndrome.
We report on the 8th patient carrying a heterozygous de novo variation of PRKD1 c.2134G > A, p. (Val712Met) identified by trio exome sequencing. The proband presents with partial atrioventricular septal defect, brachydactyly, ectodermal dysplasia, telangiectasia that developed in childhood, intellectual disability with microcephaly, multicystic renal dysplasia and moderate hormonal resistance. In view of this 8th description and review of the literature, it appears that neurodevelopmental disorders and microcephaly are frequently associated with PRKD1 missense variants, adding to the four main clinical signs described initially in the TEBC syndrome. Further descriptions are required to confirm the observed endocrine and kidney abnormalities. This should contribute to a more comprehensive understanding of the phenotypic spectrum and may help establish genotype-phenotype correlations.
In the context of genotype-first strategy, accurate patient descriptions are fundamental. Characterization of specific syndromic associations is essential for variant interpretation support and patient follow-up, even in very rare diseases, such as the TEBC syndrome.
This 1-year multicentre prospective study in northern France sought to evaluate the incidence of secondary bacterial skin complications related to varicella, describe these superinfections, and ...analyse risk factors for their onset. The study included every child admitted to a district paediatric unit with a varicella infection. Patients with varicella infection, with and without secondary bacterial skin complication, were compared. The study included 159 children, 43 of whom had a secondary bacterial skin complication on admission, 21 of them had a severe secondary bacterial skin complication (respective incidence: 7.5 and 3.7/100,000 children younger than 16 years old). Persistence or recurrence of fever > or =38.5 degrees C for > or =3 days after the beginning of varicella infection (adjusted odds ratio (aOR)=8.1; 95% confidence interval (CI): 2.3-28.4) and the use of non-steroidal anti-inflammatory drugs (aOR=4.8; 95% CI: 1.6-14.4) were independent factors associated with severe secondary bacterial skin complication.
Abstract Poikiloderma occurs in a number of hereditary syndromes, the best known of which is Rothmund–Thomson syndrome (RTS). Differential diagnoses include Dyskeratosis Congenita (DC) with high ...genetic heterogeneity and Clericuzio-type Poikiloderma with Neutropenia (CPN) due to mutations in the C16orf57 gene. Mutations in the RECQL4 gene are only observed in two thirds of RTS patients. In this study, 10 patients referred for syndromic poikiloderma and negative for RECQL4 sequencing analysis were investigated for C16orf57 mutations. Two C16orf57 heterozygous nonsense mutations (p.W81X and p.Y89X) were identified in a 5-year-old female child presenting with generalized poikiloderma, dental dysplasia, gingivitis, nail dystrophy, palmoplantar keratoderma and pachyonychia of the great toenails. Previously undetected and silent neutropenia was evidenced after C16orf57 molecular analysis. Neutropenia was absent in the C16orf57- negative patients. This report confirms that neutrophil count should be performed in all patients with poikiloderma to target the C16orf57 gene sequencing analysis, prior to RECQL4 analysis.
Syphilis cases in childhood are usually associated with congenital transmission. Acquired transmission is uncommon, and primarily related to sexual abuse or close contact/nursing with infected family ...members. We here describe a case of syphilis in a 14-month-old girl resulting from intrafamilial infection, with a subsequent transmission to her mother.
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