monarch-initiative/mondo: v2026-09-01

<details> <summary>New terms: 9</summary>

| Mondo ID | Label | Definition | |:---|:---|:---| | MONDO:0100594 | chronic idiopathic axonal polyneuropathy | Any chronic polyneuropathy with both sensory and motor involvement in a length dependant distribution where neurophysiology reveals axonal damage, neuropathy onset is insidious and shows slow or no progression of the disease over at least 6 months with no aetiology being identified despite appropriate investigations. | | MONDO:1060247 | SMARCAL1-related tumor predisposition | Hereditary tumor predisposition due to variation(s) in the SMARCAL12 gene. | | MONDO:1060248 | IMPDH2-related disorder | An ultra-rare hereditary neurological disorder caused by a variation in the IMPDH2 gene, which encodes a key enzyme involved in guanine nucleotide biosynthesis and purine metabolism. The phenotype spans a spectrum from neurodevelopmental delay, intellectual disability, dystonia, tremor, and other movement abnormalities, with variable expressivity and age of onset. | | MONDO:1060249 | atypical teratoid rhabdoid tumor, SHH-activated | An atypical teratoid rhabdoid tumor characterized by overexpression of genes in the sonic hedgehog (SHH) pathway (GLI2, BOC, PTCHD2, and MYCN). | | MONDO:1060250 | atypical teratoid rhabdoid tumor, MYC-activated | An atypical teratoid rhabdoid tumor characterized by overexpression of the MYC gene. | | MONDO:1060251 | atypical teratoid rhabdoid tumor, TYR-activated | An atypical teratoid rhabdoid tumor characterized by overexpression of melanosomal genes (TYR, TYRP, MITF, and OTX2). | | MONDO:1060252 | intracranial mesenchymal tumor, FET-CREB fusion-positive | A central nervous system mesenchymal non-meningothelial tumor with a broad morphological spectrum, characterized by fusion of a FET family gene (usually EWSR1 and rarely FUS) with a member of the CREB family of transcription factors (CREB1, ATF1, or CREM). It includes entities previously termed intracranial angiomatoid fibrous histiocytoma or intracranial myxoid mesenchymal tumor. It is usually located in the supratentorial brain and mostly affects children and young adults. There is a spectrum of clinical behaviors ranging from slowly growing tumors to rapid recurrences, and rarely metastases. | | MONDO:1060253 | desmoplastic myxoid tumor of the pineal region, SMARCB1-mutant | A pineal body neoplasm that is a SMARCB1-deficient tumor of the brain, characterized by the presence of spindled and epithelioid cells with low-grade morphology that are embedded in a desmoplastic stroma alternating with various extents of loose myxoid matrix. | | MONDO:1060254 | cribriform neuroepithelial tumor | A very rare, nonrhabdoid, intraventricular tumor with relatively favorable prognosis. It is characterized by the presence of neuroepithelial cells forming cribriform patterns, trabeculae, epithelial membrane antigen immunopositivity on epithelial surfaces, and loss of nuclear INI1 expression. |

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<details> <summary>Terms renamed (excluding obsoleted terms): 4</summary>

| Mondo ID | Old Label | New Label | |:---|:---|:---| | MONDO:0010829 | CARASIL syndrome | cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 2 | | MONDO:0100100 | SELENON-related myopathy | congenital myopathy 3 with rigid spine | | MONDO:0100009 | structural congenital heart disease, multiple types - GATA4 | GATA4-related congenital heart disease with or without pancreatic hypoplasia or diabetes | | MONDO:0100540 | GATA6-related congenital heart disease with or without pancreatic agenesis or neonatal diabetes | GATA6-related congenital heart disease with or without pancreatic hypoplasia or diabetes |

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<details> <summary>Text definitions added to existing terms: 10</summary>

| Mondo ID | Label | New Text Definition | |:---|:---|:---| | MONDO:0008554 | thrombocythemia 1 | Any familial thrombocytosis caused by a variation in the THPO gene, which encodes thrombopoietin, characterized by sustained thrombocythemia from excessive thrombopoietin signaling that ranges from asymptomatic thrombocytosis to thrombotic or hemorrhagic episodes, with rare progression to leukemic transformation. | | MONDO:0020747 | sitosterolemia 1 | Any sitosterolemia caused by a variation in the ABCG8 gene, characterized by increased intestinal absorption and reduced biliary excretion of plant sterols, leading to markedly elevated plasma sitosterol and related phytosterols, xanthomas, and premature atherosclerosis/coronary disease. Some patients develop hematologic manifestations, including stomatocytic hemolysis, macrothrombocytopenia, splenomegaly, and abnormal bleeding. In some cases the hematologic phenotype can be the presenting or only sign. Biallelic loss‑of‑function variants in ABCG8 impair the heterodimeric transporter that normally limits sterol absorption and promotes biliary sterol excretion, explaining the biochemical and clinical findings. | | MONDO:0020748 | sitosterolemia 2 | Any sitosterolemia caused by a variation in the ABCG5 gene, characterized by markedly increased intestinal absorption and reduced biliary excretion of plant sterols, resulting in extremely elevated plasma sitosterol levels, tendon and tuberous xanthomas, and premature atherosclerosis. A subset of affected individuals develop hematologic manifestations, including stomatocytic hemolysis, macrothrombocytopenia, splenomegaly, and abnormal bleeding, and in some cases these hematologic findings may be the initial or only clinical signs. Biallelic loss‑of‑function variants in ABCG5 impair the heterodimeric ABCG5/ABCG8 transporter required for limiting dietary sterol uptake and promoting biliary excretion, leading to membrane sterol accumulation in multiple blood cell types. | | MONDO:0030903 | Hermansky-Pudlak syndrome 11 | A Hermansky-Pudlak syndrome caused by biallelic variants in the BLOC1S5 gene, resulting in melanosome defects and absence of platelet dense granules, and characterized by mild oculocutaneous albinism with reduced visual acuity and a moderate platelet-type bleeding diathesis with impaired platelet aggregation and ATP release. Reported cases to date suggest a relatively mild systemic course compared with other subtypes. | | MONDO:0031009 | Glanzmann thrombasthenia 2 | A platelet type bleeding disorder characterized by lifelong mucocutaneous bleeding, severely impaired platelet aggregation, and absent or markedly reduced clot retraction due to loss of αIIbβ3‑mediated fibrinogen binding. Platelet number and morphology are typically normal, but responses to physiologic agonists, such as ADP, collagen, epinephrine, and thrombin are severely diminished or absent, while ristocetin‑induced agglutination is preserved. Biallelic loss‑of‑function ITGB3 variants result in reduced or absent β3 integrin production, preventing assembly or surface expression of the αIIbβ3 receptor complex and producing the characteristic Glanzmann thrombasthenia phenotype. | | MONDO:0044316 | thrombocytopenia, anemia, and myelofibrosis | An inherited thrombocytopenia caused by a variation in the MPIG6B gene, which impairs the inhibitory signaling of the G6b-B receptor on megakaryocytes and platelets, characterized by thrombocytopenia, variable anemia, and progressive bone-marrow fibrosis, often with splenomegaly and abnormal platelet activation and megakaryocyte maturation. | | MONDO:0060583 | platelet abnormalities with eosinophilia and immune-mediated inflammatory disease | A multisytem disorder caused by a variation in the ARPC1B gene, characterized by recurrent bacterial and viral infections beginning in infancy or early childhood, accompanied by inflammatory manifestations such as vasculitis, eczema, colitis, hepatosplenomegaly, and systemic autoinflammation. Affected individuals show congenital thrombocytopenia with variable platelet abnormalities including small, misshapen platelets and dense‑granule defect, and additional laboratory findings such as eosinophilia and elevated IgE or IgA. Functional studies demonstrate defects in neutrophil and T‑cell chemotaxis and impaired T‑cell activation caused by abnormal F‑actin polymerization, consistent with loss of ARPC1B function. | | MONDO:0859200 | cerebellar ataxia, brain abnormalities, and cardiac conduction defects | A neurodevelopmental disorder caused by a variation in the EXOSC5 gene, characterized by cerebellar ataxia, neurodevelopmental delay, poor motor development and growth, mild to severe intellectual disability and infantile-onset hypotonia. Many patients have cardiac conduction and rhythm anomalies (including bundle branch block, bradycardia, sinus node dysfunction, intraventricular conduction delay, atrioventricular block, and ventricular tachycardia) in childhood or adolescence. Some patients have thrombotic microangiopathy. Additional clinical features may includevariable ocular anomalies and dysmorphic features. | | MONDO:0957575 | amegakaryocytic thrombocytopenia, congenital, 2 | A congenital amegakaryocytic thrombocytopenia caused by a variation in the THPO gene, which encodes thrombopoietin, characterized by infantile- or early childhood-onset thrombocytopenia with markedly reduced or absent megakaryocytes, often progressing to pancytopenia, aplastic anemia, and hypocellular bone marrow, with decreased or inappropriately normal serum thrombopoietin. | | MONDO:0958000 | thrombocytopenia 11 with multiple congenital anomalies and dysmorphic facies | Any inherited thrombocytopenia caused by a variation in the RAP1B gene, which encodes a small GTPase that regulates integrin activation and RAS/MAPK signaling, characterized by chronic thrombocytopenia (often with leukopenia or lymphopenia), dysmorphic facial features, poor growth with microcephaly, hypotonia, mild intellectual or learning disability, and variable congenital anomalies of the heart, brain, skeletal, genitourinary, or endocrine systems. |

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<details> <summary>Text definitions changed: 19</summary>

| Mondo ID | Label | Old Text Definition | New Text Definition | |:---|:---|:---|:---| | MONDO:0008748 | Hermansky-Pudlak syndrome 1 | Any Hermansky-Pudlak syndrome in which the cause of the disease is a mutation in the HPS1 gene. | Any Hermansky-Pudlak syndrome in which the cause of the disease is a mutation in the HPS1 gene, causing defects of melanosomes and absence of platelet dense bodies. Core features include oculocutaneous albinism with nystagmus and reduced visual acuity, and a platelet‑type bleeding diathesis. Some individuals develop pulmonary fibrosis and/or granulomatous colitis. | | MONDO:0008822 | arthrogryposis, renal dysfunction, and cholestasis 1 | Any arthrogryposis-renal dysfunction-cholestasis syndrome in which the cause of the disease is a mutation in the VPS33B gene. | Any arthrogryposis-renal dysfunction-cholestasis syndrome in which the cause of the disease is a mutation in the VPS33B gene that disrupts apical–basolateral polarity and vesicle‑trafficking pathways essential for normal liver, kidney, and skin function. Affected individuals present with congenital joint contractures, renal tubular dysfunction, and neonatal cholestasis with low GGT, accompanied by ichthyosis, severe failure to thrive, central nervous system malformations, and platelet α‑granule defects. The condition is severe and often lethal in infancy, reflecting profound epithelial and secretory dysfunction across multiple organs. | | MONDO:0031332 | Glanzmann thrombasthenia 1 | A bleeding syndrome characterized by spontaneous mucocutaneous bleeding and an exaggerated response to trauma due to a constitutional thrombocytopenia | A plalelet type bleeding disorder characterized by lifelong mucocutaneous bleeding, markedly impaired platelet aggregation, and absent or severely reduced clot retraction due to failure of the αIIbβ3 integrin complex to bind fibrinogen. Platelets appear normal in number and morphology, but aggregation responses to physiologic agonists (including ADP, collagen, epinephrine, and thrombin) are severely decreased or absent, while ristocetin‑induced agglutination remains normal. Biallelic loss‑of‑function ITGA2B variants reduce or abolish surface expression of the αIIbβ3 receptor, preventing fibrinogen‑mediated platelet bridging and producing the classic Glanzmann thrombasthenia phenotype. | | MONDO:0010829 | cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 2 | CARASIL is a hereditary cerebral small vessel disease characterized by early-onset gait disturbances, premature scalp alopecia, ischemic stroke, acute mid to lower back pain and progressive cognitive disturbances leading to severe dementia. | An autosomal recessive cerebral arteriopathy with subcortical infarcts and leukoencephalopathy caused by a variation in the HTRA1 gene, characterized by early-onset gait disturbances, premature scalp alopecia, ischemic stroke, acute mid to lower back pain and progressive cognitive disturbances leading to severe dementia. | | MONDO:0011173 | thrombocythemia 2 | Familial thrombocytosis in which the cause of the disease is a mutation in the MPL gene. | Familial thrombocytosis in which the cause of the disease is a mutation in the MPL gene that produces constitutive activation of the thrombopoietin receptor, leading to excessive megakaryocyte proliferation and elevated platelet counts. Affected individuals exhibit sustained thrombocythemia, which may be accompanied by thrombotic or hemorrhagic complications and, in rare cases, leukemic transformation. | | MONDO:0800452 | congenital amegakaryocytic thrombocytopenia 1 | A rare inherited bone marrow failure syndrome, in which the cause of the disease is a variation in the MPL gene. It is characterized by an isolated and severe decrease in the number of platelets and megakaryocytes during the first years of life that develops into bone marrow failure with pancytopenia later in childhood. | Any congenital amegakaryocytic thrombocytopenia in which the cause of the disease is a variation in the MPL gene. It is characterized by severe decrease in the number of platelets and megakaryocytes during the first years of life that develops into bone marrow failure with pancytopenia later in childhood. The disorder reflects impaired TPO–MPL signaling leading to failure of megakaryopoiesis, but shows a favorable response to bone‑marrow transplantation. | | MONDO:0100009 | GATA4-related congenital heart disease with or without pancreatic hypoplasia or diabetes | Any congenital heart disease in which the cause of the disease is a mutation in the GATA4 gene. | Any congenital heart disease in which the cause of the disease is a mutation in the GATA4 gene, occurring with or without other syndromic features including pancreatic hypoplasia or agenesis, diabetes, and disorders of sex development. | | MONDO:0011997 | Hermansky-Pudlak syndrome 2 | A type of Hermansky-Pudlak syndrome (HPS), a multi-system disorder characterized by oculocutaneous albinism, bleeding diathesis and neutropenia. | Any Hermansky-Pudlak syndrome in which the cause of the disease is a variation in the AP3B1 gene that impairs the formation of lysosome‑related organelles, including melanosomes and platelet dense granules. It presents with oculocutaneous albinism and a platelet‑type bleeding diathesis from dense‑granule deficiency. A distinguishing feature is immunodeficiency with neutropenia and recurrent infections; pulmonary complications can occur. | | MONDO:0013255 | arthrogryposis, renal dysfunction, and cholestasis 2 | Any arthrogryposis-renal dysfunction-cholestasis syndrome in which the cause of the disease is a mutation in the VIPAS39 gene. | Any arthrogryposis-renal dysfunction-cholestasis syndrome in which the cause of the disease is a mutation in the VIPAS39 gene that disrupts vesicle‑trafficking pathways required for apical–basolateral polarity in epithelial tissues. Affected individuals present with congenital joint contractures, renal tubular dysfunction, and neonatal cholestasis, often accompanied by ichthyosis, severe failure to thrive, central nervous system anomalies, and variable platelet abnormalities. The phenotype reflects impaired function of the VIPAR–VPS33B complex in polarized liver and kidney cells, leading to widespread epithelial and secretory dysfunction. | | MONDO:0013555 | Hermansky-Pudlak syndrome 3 | Any Hermansky-Pudlak syndrome in which the cause of the disease is a mutation in the HPS3 gene. | Any Hermansky-Pudlak syndrome in which the cause of the disease is a mutation in the HPS3 gene. Affected individuals have mild oculocutaneous/ocular hypopigmentation with nystagmus and reduced visual acuity, and a generally mild bleeding diathesis. Compared with other forms, systemic complications (e.g., pulmonary fibrosis or colitis) are uncommon and the overall phenotype is milder. | | MONDO:0013556 | Hermansky-Pudlak syndrome 4 | Any Hermansky-Pudlak syndrome in which the cause of the disease is a mutation in the HPS4 gene. | Any Hermansky-Pudlak syndrome in which the cause of the disease is a mutation in the HPS4 gene that disrupts biogenesis of lysosome‑related organelles, resulting in melanosome defects and absence of platelet dense bodies. The core phenotype comprises oculocutaneous albinism with reduced visual acuity and nystagmus, and a platelet‑type bleeding tendency. Pulmonary fibrosis and/or granulomatous colitis may occur in this subtype. | | MONDO:0013557 | Hermansky-Pudlak syndrome 5 | Any Hermansky-Pudlak syndrome in which the cause of the disease is a mutation in the HPS5 gene. | Any Hermansky-Pudlak syndrome in which the cause of the disease is a mutation in the HPS5 gene, producing melanosome defects and absence of platelet dense bodies. Individuals typically show oculocutaneous albinism (often mild) with visual impairment and a platelet‑type bleeding diathesis. | | MONDO:0013560 | Hermansky-Pudlak syndrome 8 | Any Hermansky-Pudlak syndrome in which the cause of the disease is a mutation in the BLOC1S3 gene. | Any Hermansky-Pudlak syndrome in which the cause of the disease is a mutation in the BLOC1S3 gene that impairs melanosomes and platelet dense‑granule formation. Individuals show generalized hypopigmentation with visual impairment (nystagmus, foveal hypoplasia, optic pathway misrouting) and a platelet‑type bleeding diathesis. The severity of bleeding is variable across reported cases. | | MONDO:0013606 | Hermansky-Pudlak syndrome 9 | Any Hermansky-Pudlak syndrome in which the cause of the disease is a mutation in the BLOC1S6 gene. | Any Hermansky-Pudlak syndrome in which the cause of the disease is a mutation in the BLOC1S6 gene, resulting in defective melanosomes and absence of platelet dense granules. The phenotype includes oculocutaneous/ocular albinism with nystagmus and reduced visual acuity and a bleeding tendency. Distinguishing features can include leukopenia with recurrent infections and thrombocytopenia in some patients. | | MONDO:0100540 | GATA6-related congenital heart disease with or without pancreatic hypoplasia or diabetes | A congenital heart disease that is present at birth. Representative examples include atrial septal defect 9, conotruncal heart malformations, tetralogy of Fallot, ventricular septal defect, atrioventricular septal defect, bicuspid aortic valve, transposition of the great arteries, persistent truncus arteriosus, congenital heart disease with pancreatic agenesis, and congenital heart disease with neonatal diabetes. | A congenital heart disease caused by a variation in the GATA6 gene, occurring with or without other syndromic features including pancreatic hypoplasia or agenesis and diabetes. Representative cardiac examples include atrial septal defect 9, conotruncal heart malformations, tetralogy of Fallot, ventricular septal defect, atrioventricular septal defect, bicuspid aortic valve, transposition of the great arteries, and persistent truncus arteriosus. | | MONDO:0013853 | pontocerebellar hypoplasia type 1B | Any non-syndromic pontocerebellar hypoplasia in which the cause of the disease is a mutation in the EXOSC3 gene. | Any pontocerebellar hypoplasia in which the cause of the disease is a mutation in the EXOSC3 gene, which may include other brain anomalies (such as cerebellar atrophy or mega cisterna magna), hypotonia, ocular anomalies (including strabismus or vision loss), thrombotic microangiopathy, hypertension, proteinuria, and swollen or hyperechogenic kidneys. | | MONDO:0014885 | Hermansky-Pudlak syndrome 10 | Any Hermansky-Pudlak syndrome in which the cause of the disease is a mutation in the AP3D1 gene. | Any Hermansky-Pudlak syndrome in which the cause of the disease is a mutation in the AP3D1 gene disrupts AP‑3–dependent trafficking to lysosome‑related organelles, including melanosomes and platelet dense granules. Alongside oculocutaneous albinism and a platelet‑type bleeding diathesis, affected individuals develop early‑onset immunodeficiency and severe neurologic impairment (e.g., profound developmental delay and refractory seizures). Additional findings can include interstitial lung disease and hepatosplenomegaly. | | MONDO:0100083 | hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 | This is an autosomal dominant disorder caused by mutations in the RUNX1 gene and is characterized by mild to moderate thrombocytopenia, platelet functional and/or ultrastructural defects and a predisposition to hematologic malignancies, most often AML and MDS, and less frequently T-ALL. | A hereditary thrombocytopenia and hematologic cancer predisposition syndrome caused by mutations in the RUNX1 gene and is characterized by mild to moderate thrombocytopenia, platelet functional and/or ultrastructural defects and a predisposition to hematologic malignancies, most often AML and MDS, and less frequently T-ALL. | | MONDO:0100433 | ACTB-associated syndromic thrombocytopenia | A syndrome associated with developmental delay, mild intellectual disability, microcephaly, and thrombocytopenia with platelet anisotropy and enlarged platelets. | A syndromic constitutional thrombocytopenia caused by a variation in the ACTB gene, associated with developmental delay, mild intellectual disability, microcephaly, and thrombocytopenia with platelet anisotropy and enlarged platelets. Unlike many inherited platelet disorders, spontaneous bleeding is often limited, and the phenotype reflects a combined disturbance of platelet formation and neurodevelopmental and craniofacial patterning. |

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<details> <summary>Terms obsoleted with replacement: 2</summary>

| Mondo ID | Label | Replacement | |:---|:---|:---| | MONDO:0011271 | obsolete rigid spine muscular dystrophy 1 | congenital myopathy 3 with rigid spine (MONDO:0100100) | | MONDO:0019398 | obsolete desmin-related myopathy with Mallory body-like inclusions | congenital myopathy 3 with rigid spine (MONDO:0100100) |

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<details> <summary>Terms obsoleted without replacement: 0</summary>

| Mondo ID | Label | |:---|:---|

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<details> <summary>New obsoletion candidates: 6</summary>

| Mondo ID | Label | |:---|:---| | MONDO:0004323 | muscular atrophy | | MONDO:0015793 | moderate multiminicore disease with hand involvement | | MONDO:0017939 | classic multiminicore myopathy | | MONDO:0018832 | HTRA1-related autosomal dominant cerebral small vessel disease | | MONDO:0032733 | global developmental delay, progressive ataxia, and elevated glutamine | | MONDO:0100307 | adult Refsum disease due to PEX7 defect |

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<details> <summary>Terms that were previously candidates for obsoletion and are now not anymore: 0</summary>

| Mondo ID | Label | |:---|:---|

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