MECOM-associated syndrome: a heterogeneous inherited bone marrow failure syndrome with amegakaryocytic thrombocytopenia

Abstract

Key Points Germ line mutations in MECOM cause a heterogeneous bone marrow failure syndrome with congenital hypomegakaryocytic thrombocytopenia. MECOM-associated syndrome includes various organ malformations with variable penetrance, including radioulnar synostosis.

New MECOM variant in a child with severe neonatal cytopenias spontaneously resolving

“…Constitutional (germline) heterozygous variants in MECOM gene have been described in a total of 27 patients to date. [1][2][3][4][5][6] Thrombocytopenia is the main hematological manifestation, reported in all cases (Table S1). A progressive deterioration toward bone marrow failure occurred in 21 of 27 patients, all except two of whom underwent hematopoietic stem cell transplantation (HSCT) at a median age (range) of 0.9 years (0.25-48).…”

“…[8][9][10] The phenotype of constitutional MECOM variant is heterogeneous with both hematologic and extra-hematologic manifestations. [1][2][3][4][5][6] The diagnosis is frequently made in infancy. The disease course of our patient is uncommon as the initial severe presentation progressively normalized.…”

“…These proteins are zinc finger transcription factors playing an important role in the formation and self‐renewal of hematopoietic stem cells as well as myeloid differentiation 8–10 . The phenotype of constitutional MECOM variant is heterogeneous with both hematologic and extra‐hematologic manifestations 1–6 . The diagnosis is frequently made in infancy.…”

A novel mutation in the MECOM gene causing radioulnar synostosis with amegakaryocytic thrombocytopenia (RUSAT‐2) in an infant

“…Radioulnar synostosis with amegakaryocytic thrombocytopenia (RUSAT [MIM: 605432]) is a rare inherited bone marrow failure syndrome (IBMFS) with skeletal anomalies . Although majority of RUSAT syndromes are caused by HOXA11 mutations, a subset with varied MECOM gene mutations has been described . Niihori et al identified heterozygous mutations in MECOM in three patients with RUSAT and named this genotype RUSAT‐2 (MIM #616738) .…”

“…Bluteau et al identified six patients with MECOM mutations in a large cohort of IBMFS . A recent report of 12 cases with MECOM mutations revealed clinical spectrum ranging from isolated radioulnar synostosis to severe bone marrow failure without skeletal abnormalities, indicating wide spectrum and varied penetrance, as seen in the proband's father . Another report suggested MECOM being a candidate gene for hereditary hematological malignancies …”