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Outi Mäkitie - One of the best experts on this subject based on the ideXlab platform.
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Gynecologic health in Cartilage-Hair Hypoplasia: A survey of 26 adult females.
American journal of medical genetics. Part A, 2018Co-Authors: Elina Holopainen, Svetlana Vakkilainen, Outi MäkitieAbstract:Cartilage-Hair Hypoplasia (CHH) is a rare metaphyseal chondrodysplasia significantly affecting adult height and quality of life. Immunodeficiency and increased risk for malignancies contribute to significant morbidity. Little is known about gynecologic health in CHH. We performed a questionnaire study of 26 women (mean age 42.3 years) with genetically confirmed CHH, inquiring about pubertal development, menstrual cycle, use of contraception, pregnancies, gynecologic infections, and gynecologic cancers. Mean age at menarche and menopause was 12.7 and 46.1 years, respectively. Mean length of menstrual cycle was 27 days. Contraception was used by 76%, most commonly condom (60%), and combined contraception (60%). Despite significant short stature (mean height 121 cm) and potentially small pelvic diameters, 10 CHH women (38%) had been pregnant. Six of these women reported miscarriages and three had, induced pregnancy terminations. Eight women had in total, 19 deliveries. Abnormal Pap smear was reported in five patients and cervical cancer once. Our findings of normal timing of puberty and menopause suggest a fairly normal length of the fertility period in women with CHH. However, many patients expressed concerns regarding the safety of pregnancy and lack of prepregnancy counseling. Immunodeficiency may predispose CHH women to prolonged HPV infections. This study highlights the importance of careful gynecologic follow-up for these patients.
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Gynecologic assessment of 19 adult females with Cartilage-Hair Hypoplasia - high rate of HPV positivity.
Orphanet journal of rare diseases, 2018Co-Authors: Elina Holopainen, Svetlana Vakkilainen, Outi MäkitieAbstract:Background Patients with Cartilage-Hair Hypoplasia (CHH), a rare metaphyseal chondrodysplasia, manifest severe growth failure, variable immunodeficiency and increased risk of malignancies. The impact of CHH on gynecologic and reproductive health is unknown. Vulnerability to genital infections may predispose CHH patients to prolonged human papillomavirus (HPV) infections potentially leading to cervical, vaginal and vulvar cancer.
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Diversity of Pubertal Development in Cartilage-Hair Hypoplasia; Two Illustrative Cases.
Journal of pediatric and adolescent gynecology, 2018Co-Authors: Elina Holopainen, Svetlana Vakkilainen, Outi MäkitieAbstract:Abstract Background Cartilage-Hair Hypoplasia (CHH) is a rare chondrodysplasia, including disproportionate short stature, hypoplastic hair, immunodeficiency, and increased risk of malignancies. Absent pubertal growth spurt and absent pubic hair complicate monitoring of pubertal development in these patients. Cases Two CHH patients with delayed puberty and excessive growth failure are described. One of the girls had hypogonadotropic hypogonadism whereas the other had hyponormogonadotropic hypogonadism with no spontaneous pubertal development and slow response to estrogen therapy, both requiring permanent replacement therapy. Summary and Conclusion Careful follow-up of pubertal development in individuals with CHH and other growth-restricting bone diseases is needed. In delayed pubertal development timely hormone therapy is essential to ensure maximal growth and well developed secondary sex characteristics.
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Cartilage-Hair Hypoplasia with normal height in childhood-4 patients with a unique genotype.
Clinical genetics, 2017Co-Authors: Paula Klemetti, Svetlana Kostjukovits, Mervi Taskinen, Sanna Toiviainen-salo, Helena Valta, Outi MäkitieAbstract:The manifestations of Cartilage-Hair Hypoplasia (CHH), a metaphyseal chondrodysplasia caused by RMRP mutations, include short stature, hypoplastic hair, immunodeficiency and increased risk of malignancies. Clinical features show significant variability. We report a patient with normal height until age 12.5 years (−1.6 SDS at 11 years) who was diagnosed with CHH at 14 years. RMRP sequencing revealed compound heterozygosity for g.70A>G mutation and a 10-nucleotide duplication at position −13 (TACTCTGTGA). Through the Finnish Skeletal Dysplasia Register we identified three additional patients with identical genotype. Two of them also showed unusually mild growth failure (height SDS −1.6 at 14 years and −3.0 at 12 years respectively). Three of the four patients suffered from recurrent infections; one developed progressive bronchiectasis and another died from aggressive lymphoma. Our findings expand the phenotypic variability in CHH to include normal childhood height. The milder growth retardation related to this particular genotype was not associated with less severe extra-skeletal manifestations, emphasizing the need for careful follow-up also in those CHH patients with mild skeletal manifestations.
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Decreased telomere length in children with Cartilage-Hair Hypoplasia
Journal of medical genetics, 2016Co-Authors: Svetlana Kostjukovits, Sofie Degerman, Minna Pekkinen, Paula Klemetti, Mattias Landfors, Göran Roos, Mervi Taskinen, Outi MäkitieAbstract:Background Cartilage-Hair Hypoplasia (CHH) is an autosomal recessive chondrodysplasia caused by RMRP (RNA component of mitochondrial RNA processing endoribonuclease) gene mutations. Manifestations ...
Ilkka Kaitila - One of the best experts on this subject based on the ideXlab platform.
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Clinical and genetic distinction of Schimke immuno-osseous dysplasia and Cartilage-Hair Hypoplasia.
American Journal of Medical Genetics Part A, 2008Co-Authors: Alireza Baradaran-heravi, Christian T. Thiel, Anita Rauch, Martin Zenker, Cornelius F. Boerkoel, Ilkka KaitilaAbstract:Previously we had proposed that Cartilage-Hair Hypoplasia (CHH) and Schimke immunoosseous dysplasia (SIOD) could be caused by defects in the same biological pathway. This was based on the shared features of skeletal dysplasia, defective T cell proliferation, and impaired lymphocytic production of and responsiveness to interleukin-2 [Boerkoel et al., 2000]. We now show that these two disorders are molecularly as well as phenotypically distinct.
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Hirschsprung's disease in Cartilage-Hair Hypoplasia has poor prognosis.
Journal of pediatric surgery, 2002Co-Authors: Outi Mäkitie, Ilkka Kaitila, Marja Heikkinen, Risto RintalaAbstract:Abstract Purpose: Cartilage-Hair Hypoplasia (CHH) is a chondrodysplasia with growth failure, impaired immunity, and high incidence of Hirschsprung disease (HD). This study describes the outcome of CHH patients with HD. Methods: Among 147 patients with CHH, 13 were identified to have HD. Their medical records were analyzed for treatment, outcome, and complications of HD and compared with a control group of 169 patients with HD but not CHH. Results: Eight CHH patients had classic HD with rectosigmoid involvement, 2 had long segment colonic disease, and 3 patients had total colonic aganglionosis. Six of the 13 CHH patients (46%) had episodes of enterocolitis before the first surgery. Enterocolitis was complicated by colonic perforation in 2 cases. Eleven CHH patients (85%) had at least one episode of postoperative enterocolitis. Five patients (38%) with CHH and HD had died; 4 of enterocolitis-related septic infection and one of non-Hodgkin's lymphoma. In the control group, preoperative enterocolitis occurred in 14% and postoperative enterocolitis in 8%. Two controls (1.2%) had died. Conclusions: HD associated with CHH has poor prognosis in terms of postoperative morbidity and risk of death. These patients require particular attention during postoperative follow-up to detect potentially lethal complications. J Pediatr Surg 37:1585-1588. Copyright 2002, Elsevier Science (USA). All rights reserved.
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Increased mortality in Cartilage-Hair Hypoplasia
Archives of disease in childhood, 2001Co-Authors: Outi Mäkitie, Eero Pukkala, Ilkka KaitilaAbstract:Background—Cartilage‐hair Hypoplasia (CHH) is an autosomal recessive chondrodysplasia with severe growth failure and impaired immunity. Impaired immunity may result in increased mortality. Aims—To follow a cohort of 120 CHH patients for mortality from 1971 to 1995. Methods—The overall and cause specific disease mortality rates in patients with CHH,and the disease mortality rate in 194 parents and 158 non-aVected sibs were compared with the national rates. Results—During follow up seven disease related deaths were observed versus 0.8 expected (standardised mortality ratio 9.3, 95% confidence interval 3.7 to 19). In most cases, the deaths were confined to the younger age groups and associated with defective immunity. The mortality of the parents and the non-aVected sibs was similar to that in the general population. Conclusion—The study confirms increased mortality in patients with CHH attributable to defective immunity, especially in children. (Arch Dis Child 2001;84:65‐67)
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Hirschsprung disease associated with severe Cartilage-Hair Hypoplasia.
The Journal of pediatrics, 2001Co-Authors: Outi Mäkitie, Ilkka Kaitila, Risto RintalaAbstract:Cartilage-Hair Hypoplasia is a chondrodysplasia with a high incidence of Hirschsprung disease. This study suggests that Hirschsprung disease is associated especially with severe Cartilage-Hair Hypoplasia: the patients with Hirschsprung disease had severe growth failure and a higher incidence of alopecia, infections, malignancies, and childhood anemia than the patients with Cartilage-Hair Hypoplasia who did not have Hirschsprung disease.
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Deficiency of humoral immunity in Cartilage-Hair Hypoplasia.
The Journal of Pediatrics, 2000Co-Authors: Outi Mäkitie, Ilkka Kaitila, Erkki SavilahtiAbstract:Abstract Objective: Cartilage-Hair Hypoplasia (CHH), a metaphyseal chondrodysplasia, is usually associated with impaired cellular immunity. This study evaluates humoral immunity in patients with CHH. Methods: The concentrations of immunoglobulins G, A, and M (IgG, IgA, and IgM) and IgG subclasses were studied in 20 patients. Data for 5 additional patients with recurrent infections were retrospectively reviewed. Results: Seven of the prospectively evaluated patients (35%) had defective humoral immunity. Three patients had IgA deficiency. Four patients had IgG2 deficiency, accompanied by IgA deficiency, IgG4 deficiency, or both in 3 patients. IgG4 was low in most patients. Increased infections were usually associated with supranormal IgG and IgG1 and subnormal IgA, IgG2, or IgG4 concentrations. One retrospectively reviewed patient had severe hypogammaglobulinemia, and 3 had multiple IgG subclass deficiencies. Conclusions: Humoral immunity is impaired in CHH and contributes to the increased susceptibility to infections. (J Pediatr 2000;137:487-92)
Jukka Rajantie - One of the best experts on this subject based on the ideXlab platform.
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Defective in-vitro colony formation of haematopoietic progenitors in patients with Cartilage-Hair Hypoplasia and history of anaemia
European Journal of Pediatrics, 1995Co-Authors: Eeva Juvonen, Outi Mäkitie, Ilkka Kaitila, Tapani Ruutu, Anne Mäkipernaa, Jukka RajantieAbstract:Cartilage-Hair Hypoplasia (CHH) is a metaphyseal chondrodysplasia with short-limbed short stature. The CHH gene has been recently mapped to chromosome 9, and a generalized defect in cellular proliferation has been suggested. Immunological and haematological abnormalities are common findings in CHH. In the present study erythroid, megakaryocyte, and granulocyte-macrophage colony formation in vitro by progenitors from bone marrow and blood was investigated in eight patients with CHH. All patients showed decreased erythroid and megakaryocyte colony formation. Only one patient had a normal granulocyte-macrophage growth, while the others showed decreased numbers of colonies. The defect in colony formation did not correlate with the haemoglobin concentration, platelet count or neutrophil count. The impaired growth was not caused by a decreased number of progenitors as shown by erythroid cultures. The erythroid progenitors were incapable of colony formation in culture conditions sufficient for colony formation by normal progenitors. In a more effectively stimulated culture assay the number of erythroid progenitors was normal or increased. Conclusion The present study shows defective in vitro colony formation in all myeloid lineages in patients with CHH, which is in accordance with the suggestion of a common cell proliferation defect in CHH.
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Defective in-vitro colony formation of haematopoietic progenitors in patients with Cartilage-Hair Hypoplasia and history of anaemia.
European Journal of Pediatrics, 1994Co-Authors: Eeva Juvonen, Outi Mäkitie, Ilkka Kaitila, Tapani Ruutu, Anne Mäkipernaa, Jukka RajantieAbstract:Cartilage-Hair Hypoplasia (CHH) is a metaphyseal chondrodysplasia with short-limbed short stature. The CHH gene has been recently mapped to chromosome 9, and a generalized defect in cellular proliferation has been suggested. Immunological and haematological abnormalities are common findings in CHH. In the present study erythroid, megakaryocyte, and granulocyte-macrophage colony formation in vitro by progenitors from bone marrow and blood was investigated in eight patients with CHH. All patients showed decreased erythroid and megakaryocyte colony formation. Only one patient had a normal granulocyte-macrophage growth, while the others showed decreased numbers of colonies. The defect in colony formation did not correlate with the haemoglobin concentration, platelet count or neutrophil count. The impaired growth was not caused by a decreased number of progenitors as shown by erythroid cultures. The erythroid progenitors were incapable of colony formation in culture conditions sufficient for colony formation by normal progenitors. In a more effectively stimulated culture assay the number of erythroid progenitors was normal or increased.
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Anaemia and macrocytosis--unrecognized features in Cartilage-Hair Hypoplasia.
Acta paediatrica (Oslo Norway : 1992), 1992Co-Authors: Outi Mäkitie, Jukka Rajantie, Ilkka KaitilaAbstract:Cartilage-Hair Hypoplasia is an autosomal recessive osteo-chondrodysplasia which results in short stature, sparse hair and impaired cell-mediated immunity. In a study of 88 Finnish patients we found episodes of anaemia and/or macrocytosis during childhood in 86% of the patients. The reticulocyte index was always low in relation to anaemia. Bone marrow examination revealed decreased erythropoiesis in six of eight anaemic patients studied. Anaemia was most prevalent and severe during infancy. Spontaneous recovery occurred before adulthood in all patients except in three infants with fatal hypoplastic anaemia. Sixty-two percent of the patients had had lymphopenia and 24% neutropenia. Presence of anaemia significantly correlated to severity of immunodeficiency and growth failure and to presence of neutropenia. Disordered erythrogenesis is an integral feature of Cartilage-Hair Hypoplasia and may, together with growth failure and immunodeficiency, reflect a generalized defect in cellular proliferation.
Eeva Juvonen - One of the best experts on this subject based on the ideXlab platform.
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Defective in-vitro colony formation of haematopoietic progenitors in patients with Cartilage-Hair Hypoplasia and history of anaemia
European Journal of Pediatrics, 1995Co-Authors: Eeva Juvonen, Outi Mäkitie, Ilkka Kaitila, Tapani Ruutu, Anne Mäkipernaa, Jukka RajantieAbstract:Cartilage-Hair Hypoplasia (CHH) is a metaphyseal chondrodysplasia with short-limbed short stature. The CHH gene has been recently mapped to chromosome 9, and a generalized defect in cellular proliferation has been suggested. Immunological and haematological abnormalities are common findings in CHH. In the present study erythroid, megakaryocyte, and granulocyte-macrophage colony formation in vitro by progenitors from bone marrow and blood was investigated in eight patients with CHH. All patients showed decreased erythroid and megakaryocyte colony formation. Only one patient had a normal granulocyte-macrophage growth, while the others showed decreased numbers of colonies. The defect in colony formation did not correlate with the haemoglobin concentration, platelet count or neutrophil count. The impaired growth was not caused by a decreased number of progenitors as shown by erythroid cultures. The erythroid progenitors were incapable of colony formation in culture conditions sufficient for colony formation by normal progenitors. In a more effectively stimulated culture assay the number of erythroid progenitors was normal or increased. Conclusion The present study shows defective in vitro colony formation in all myeloid lineages in patients with CHH, which is in accordance with the suggestion of a common cell proliferation defect in CHH.
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Defective in-vitro colony formation of haematopoietic progenitors in patients with Cartilage-Hair Hypoplasia and history of anaemia.
European Journal of Pediatrics, 1994Co-Authors: Eeva Juvonen, Outi Mäkitie, Ilkka Kaitila, Tapani Ruutu, Anne Mäkipernaa, Jukka RajantieAbstract:Cartilage-Hair Hypoplasia (CHH) is a metaphyseal chondrodysplasia with short-limbed short stature. The CHH gene has been recently mapped to chromosome 9, and a generalized defect in cellular proliferation has been suggested. Immunological and haematological abnormalities are common findings in CHH. In the present study erythroid, megakaryocyte, and granulocyte-macrophage colony formation in vitro by progenitors from bone marrow and blood was investigated in eight patients with CHH. All patients showed decreased erythroid and megakaryocyte colony formation. Only one patient had a normal granulocyte-macrophage growth, while the others showed decreased numbers of colonies. The defect in colony formation did not correlate with the haemoglobin concentration, platelet count or neutrophil count. The impaired growth was not caused by a decreased number of progenitors as shown by erythroid cultures. The erythroid progenitors were incapable of colony formation in culture conditions sufficient for colony formation by normal progenitors. In a more effectively stimulated culture assay the number of erythroid progenitors was normal or increased.
Anne Mäkipernaa - One of the best experts on this subject based on the ideXlab platform.
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Defective in-vitro colony formation of haematopoietic progenitors in patients with Cartilage-Hair Hypoplasia and history of anaemia
European Journal of Pediatrics, 1995Co-Authors: Eeva Juvonen, Outi Mäkitie, Ilkka Kaitila, Tapani Ruutu, Anne Mäkipernaa, Jukka RajantieAbstract:Cartilage-Hair Hypoplasia (CHH) is a metaphyseal chondrodysplasia with short-limbed short stature. The CHH gene has been recently mapped to chromosome 9, and a generalized defect in cellular proliferation has been suggested. Immunological and haematological abnormalities are common findings in CHH. In the present study erythroid, megakaryocyte, and granulocyte-macrophage colony formation in vitro by progenitors from bone marrow and blood was investigated in eight patients with CHH. All patients showed decreased erythroid and megakaryocyte colony formation. Only one patient had a normal granulocyte-macrophage growth, while the others showed decreased numbers of colonies. The defect in colony formation did not correlate with the haemoglobin concentration, platelet count or neutrophil count. The impaired growth was not caused by a decreased number of progenitors as shown by erythroid cultures. The erythroid progenitors were incapable of colony formation in culture conditions sufficient for colony formation by normal progenitors. In a more effectively stimulated culture assay the number of erythroid progenitors was normal or increased. Conclusion The present study shows defective in vitro colony formation in all myeloid lineages in patients with CHH, which is in accordance with the suggestion of a common cell proliferation defect in CHH.
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Defective in-vitro colony formation of haematopoietic progenitors in patients with Cartilage-Hair Hypoplasia and history of anaemia.
European Journal of Pediatrics, 1994Co-Authors: Eeva Juvonen, Outi Mäkitie, Ilkka Kaitila, Tapani Ruutu, Anne Mäkipernaa, Jukka RajantieAbstract:Cartilage-Hair Hypoplasia (CHH) is a metaphyseal chondrodysplasia with short-limbed short stature. The CHH gene has been recently mapped to chromosome 9, and a generalized defect in cellular proliferation has been suggested. Immunological and haematological abnormalities are common findings in CHH. In the present study erythroid, megakaryocyte, and granulocyte-macrophage colony formation in vitro by progenitors from bone marrow and blood was investigated in eight patients with CHH. All patients showed decreased erythroid and megakaryocyte colony formation. Only one patient had a normal granulocyte-macrophage growth, while the others showed decreased numbers of colonies. The defect in colony formation did not correlate with the haemoglobin concentration, platelet count or neutrophil count. The impaired growth was not caused by a decreased number of progenitors as shown by erythroid cultures. The erythroid progenitors were incapable of colony formation in culture conditions sufficient for colony formation by normal progenitors. In a more effectively stimulated culture assay the number of erythroid progenitors was normal or increased.