Congenital amegakaryocytic thrombocytopenia-1 (CAMT1) is an autosomal recessive disorder characterized by onset of thrombocytopenia and megakaryocytopenia in infancy or early childhood. The disorder is progressive and evolves to pancytopenia and bone marrow failure. Serum thrombopoietin is elevated. There is a favorable response to bone marrow transplantation (Muraoka et al., 1997; King et al., 2005). Genetic Heterogeneity of Congenital Amegakaryocytic Thrombocytopenia CAMT2 (620481) is caused by mutation in the THPO gene (600044) on chromosome 3q27.

Noonan syndrome (NS) is characterized by characteristic facies, short stature, congenital heart defect, and developmental delay of variable degree. Other findings can include broad or webbed neck, unusual chest shape with superior pectus carinatum and inferior pectus excavatum, cryptorchidism, varied coagulation defects, lymphatic dysplasias, and ocular abnormalities. Although birth length is usually normal, final adult height approaches the lower limit of normal. Congenital heart disease occurs in 50%-80% of individuals. Pulmonary valve stenosis, often with dysplasia, is the most common heart defect and is found in 20%-50% of individuals. Hypertrophic cardiomyopathy, found in 20%-30% of individuals, may be present at birth or develop in infancy or childhood. Other structural defects include atrial and ventricular septal defects, branch pulmonary artery stenosis, and tetralogy of Fallot. Up to one fourth of affected individuals have mild intellectual disability, and language impairments in general are more common in NS than in the general population.

Radioulnar synostosis with amegakaryocytic thrombocytopenia (RUSAT) is characterized by thrombocytopenia that progresses to pancytopenia, in association with congenital proximal fusion of the radius and ulna that results in extremely limited pronation and supination of the forearm (summary by Niihori et al., 2015). Genetic Heterogeneity of Radioulnar Synostosis with Amegakaryocytic Thrombocytopenia Radioulnar synostosis with amegakaryocytic thrombocytopenia-2 (RUSAT2; 616738) is caused by heterozygous mutation in the MECOM gene (165215) on chromosome 3q26.