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'Metaphyseal dysplasia without hypotrichosis' can present with late-onset extraskeletal manifestations.

ABSTRACT: BACKGROUND:Metaphyseal dysplasia without hypotrichosis (MDWH) is a rare form of chondrodysplasia with no extraskeletal manifestations. MDWH is caused by RMRP mutations, but it is differentiated from the allelic condition cartilage-hair hypoplasia (CHH), which in addition to chondrodysplasia is characterised by thin hair, immunodeficiency and increased risk of malignancy. The long-term outcome of MDWH remains unknown. OBJECTIVE:We diagnosed severe agranulocytosis in a subject with RMRP mutations and normal hair. Based on this observation, we hypothesised that MDWH may, similar to CHH, associate with immune deficiency and malignancy. METHODS:We collected clinical and laboratory data for a cohort of 80 patients with RMRP mutations followed for over 30 years and analysed outcome data for those with features consistent with MDWH. RESULTS:In our cohort, we identified 10 patients with skeletal but no extraskeletal features during preschool age. Eight of these patients developed malignancy or clinically significant immunodeficiency during follow-up. Two of them died during chemotherapy for malignancy. At the time of the first extraskeletal manifestation, patients were school aged, 20, 43 and 50 years old. Laboratory signs of immunodeficiency (impaired lymphocyte proliferative responses) were demonstrated in four patients before the onset of symptoms. The patient outside this cohort, who had RMRP mutations, skeletal dysplasia, normal hair and severe agranulocytosis at 18 years of age, underwent haematopoietic stem cell transplantation. CONCLUSIONS:MDWH can present with severe late-onset extraskeletal manifestations and thus should be reclassified and managed as CHH.

SUBMITTER: Vakkilainen S

PROVIDER: S-EPMC6929920 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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'Metaphyseal dysplasia without hypotrichosis' can present with late-onset extraskeletal manifestations.

Vakkilainen Svetlana S Costantini Alice A Taskinen Mervi M Wartiovaara-Kautto Ulla U Mäkitie Outi O

Journal of medical genetics 20190814 1

<h4>Background</h4>Metaphyseal dysplasia without hypotrichosis (MDWH) is a rare form of chondrodysplasia with no extraskeletal manifestations. MDWH is caused by <i>RMRP</i> mutations, but it is differentiated from the allelic condition cartilage-hair hypoplasia (CHH), which in addition to chondrodysplasia is characterised by thin hair, immunodeficiency and increased risk of malignancy. The long-term outcome of MDWH remains unknown.<h4>Objective</h4>We diagnosed severe agranulocytosis in a subjec ...[more]

PMID: 31413121

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Project description:Bronchopulmonary dysplasia (BPD) is the most common respiratory disorder among infants born extremely preterm. The pathogenesis of BPD involves multiple prenatal and postnatal mechanisms affecting the development of a very immature lung. Their combined effects alter the lung's morphogenesis, disrupt capillary gas exchange in the alveoli, and lead to the pathological and clinical features of BPD. The disorder is ultimately the result of an aberrant repair response to antenatal and postnatal injuries to the developing lungs. Neonatology has made huge advances in dealing with conditions related to prematurity, but efforts to prevent and treat BPD have so far been only partially effective. Seeing that BPD appears to have a role in the early origin of chronic obstructive pulmonary disease, its prevention is pivotal also in long-term respiratory outcome of these patients. There is currently some evidence to support the use of antenatal glucocorticoids, surfactant therapy, protective noninvasive ventilation, targeted saturations, early caffeine treatment, vitamin A, and fluid restriction, but none of the existing strategies have had any significant impact in reducing the burden of BPD. New areas of research are raising novel therapeutic prospects, however. For instance, early topical (intratracheal or nebulized) steroids seem promising: they might help to limit BPD development without the side effects of systemic steroids. Evidence in favor of stem cell therapy has emerged from several preclinical trials, and from a couple of studies in humans. Mesenchymal stromal/stem cells (MSCs) have revealed a reparatory capability, preventing the progression of BPD in animal models. Administering MSC-conditioned media containing extracellular vesicles (EVs) have also demonstrated a preventive action, without the potential risks associated with unwanted engraftment or the adverse effects of administering cells. In this paper, we explore these emerging treatments and take a look at the revolutionary changes in BPD and neonatology on the horizon.

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'Metaphyseal dysplasia without hypotrichosis' can present with late-onset extraskeletal manifestations.

Publications

'Metaphyseal dysplasia without hypotrichosis' can present with late-onset extraskeletal manifestations.

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