A case report of familial dyskeratosis congenital. Case report

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Abstract

Dyskeratosis congenita (DC) is a hereditary syndrome of bone marrow failure, which develops because of telomeres’ defects and combines with cancer predisposition. Its classical clinical features are skin pigmentation, nail dystrophy, oral leukoplakia (“skin-mucosa triad”). The goal is to describe the algorithm of diagnosis, clinical specificities of DC and specific treatment for cases of DC in one family. The present report includes descriptions of diagnosis and treatment of family members diagnosed for the first time as having a DC. The report shows an importance of all diagnostic stages: from a medical history and clinical picture to an application of modern high-tech diagnostic methods (flow-FISH, NGS). The report underlines an importance of diagnosis of all family members for excluding an asymptomatic form after a case of DC has been already detected in that family. A high frequency of a toxicity and secondary neoplasia makes it necessary to realize an individual approach at treatment of each patient with DC (the earliest start of androgen treatment, prompt decision of implementation of allogenic hematopoietic stem cell transplantation). The knowledge of pathogenesis, clinical features and principles of diagnosis and therapy of this disease is relevant to pediatricians and hematologists.

About the authors

Anton V. Luchkin

National Research Center for Hematology

Author for correspondence.
Email: a_luchkin@rambler.ru
ORCID iD: 0000-0002-4400-4711

врач-гематолог отд-ния интенсивной высокодозной химиотерапии гемобластозов и депрессий кроветворения

Russian Federation, Moscow

Elena A. Mikhailova

National Research Center for Hematology

Email: a_luchkin@rambler.ru
ORCID iD: 0000-0002-2449-2682

д-р мед. наук, проф., вед. науч. сотр. отд-ния интенсивной высокодозной химиотерапии гемобластозов и депрессий кроветворения

Russian Federation, Moscow

Zalina T. Fidarova

National Research Center for Hematology

Email: a_luchkin@rambler.ru
ORCID iD: 0000-0003-0934-6094

канд. мед. наук, зав. отд-нием химиотерапии гемобластозов и депрессий кроветворения с дневным стационаром

Russian Federation, Moscow

Vera V. Troitskaya

National Research Center for Hematology

Email: a_luchkin@rambler.ru
ORCID iD: 0000-0002-4827-8947

канд. мед. наук, зам. дир. по лечебной работе, зав. отд-нием высокодозной химиотерапии гемобластозов и депрессий кроветворения

Russian Federation, Moscow

Irina V. Galtseva

National Research Center for Hematology

Email: a_luchkin@rambler.ru
ORCID iD: 0000-0002-8490-6066

канд. мед. наук, зав. лаб. иммунофенотипирования клеток крови и костного мозга

Russian Federation, Moscow

Alla M. Kovrigina

National Research Center for Hematology

Email: a_luchkin@rambler.ru
ORCID iD: 0000-0002-1082-8659

д-р биол. наук, зав. патологоанатомическим отд-нием

Russian Federation, Moscow

Svetlana A. Glinkina

National Research Center for Hematology

Email: a_luchkin@rambler.ru
ORCID iD: 0000-0002-7321-1728

врач-патологоанатом патологоанатомического отделения

Russian Federation, Moscow

Valentina N. Dvirnyk

National Research Center for Hematology

Email: a_luchkin@rambler.ru
ORCID iD: 0000-0002-9877-0796

канд. мед. наук, зав. централизованной клинико-диагностической лаб.

Russian Federation, Moscow

Elena V. Raykina

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology

Email: a_luchkin@rambler.ru
ORCID iD: 0000-0002-7634-2053

канд. мед. наук, зав. лаб. молекулярной биологии

Russian Federation, Moscow

Anna V. Pavlova

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology

Email: a_luchkin@rambler.ru
ORCID iD: 0000-0002-3974-5662

мл. науч. сотр. лаб. молекулярной биологии

Russian Federation, Moscow

Irina A. Demina

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology

Email: a_luchkin@rambler.ru
ORCID iD: 0000-0002-4317-2094

канд. биол. наук, врач клинической лабораторной диагностики лаб. клеточной иммунологии и иммуногенеза

Russian Federation, Moscow

Elena N. Parovichnikova

National Research Center for Hematology

Email: a_luchkin@rambler.ru
ORCID iD: 0000-0001-6177-3566

д-р мед. наук, зав. отд-нием химиотерапии гемобластозов, депрессий кроветворения и ТКМ

Russian Federation, Moscow

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2. Fig. 1. Reticular pigmentation on P-1’s skin of lower extremities.

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3. Fig. 2. Histochemistry, immunohistochemistry and histochemistry of P-1’s bone marrow trephine biopsy: а – bone marrow trephine biopsy. In wide bone marrow cavities is a hypercellular bone marrow, the growth of erythroid lineage with dyserythropoiesis, a rejuvenation of granulocyte lineage cells. Hematoxylin and eosin stain; ×200; b – reaction with anti-CD42b antibodies. An increased number of small megakaryocytes with monolobular nuclei, microforms = the features of dysmegakaryocytopoesis. enzyme-linked immunosorbent assay; ×200; c – the decree of fibrosis of stroma is MF 2 with sites of MF-3 according to the European Consensus on grading. Gomori's stain; ×200.

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4. Fig. 3. Reticular pigmentation on P-2’s skin of neck and oral leukoplakia.

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5. Fig. 4. The identified mutations in members of the family, which are responsible for occurrence of dyskeratosis congenita (DC).

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6. Fig. 5. The algorithm of patient’s examination with a possible DC.

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