monarch-initiative/mondo: v2026-08-04

<details> <summary>New terms: 10</summary>

| Mondo ID | Label | Definition | |:---|:---|:---| | MONDO:1060234 | P2RY12-related platelet disorder, autosomal dominant | A platelet type bleeding disorder of autosomal dominant inheritance caused by a variation in the P2RY12 gene that exerts a dominant negative effect by disrupting receptor homodimerization, leading to markedly impaired adenosine diphosphate induced platelet aggregation despite normal receptor expression. Affected individuals may exhibit severe bleeding symptoms due to defective amplification of platelet activation signals. | | MONDO:1060237 | GP9-related Bernard-Soulier syndrome | Any Bernard-Soulier syndrome caused by the variation in the GP9 gene, marked by absent or markedly reduced GPIb-IX-V complex expression, resulting in impaired platelet adhesion and lifelong mucocutaneous bleeding. Platelets are large and functionally deficient, with severely reduced ristocetin-induced agglutination reflecting loss of functional GPIX within the receptor complex. Variants in GP9 disrupt synthesis or stability of the GPIX subunit, preventing proper assembly of the GPIb-IX-V complex and producing the characteristic bleeding phenotype. | | MONDO:1060238 | GP1BA-related Bernard-Soulier syndrome | Any Bernard-Soulier syndrome in which the cause of the disease is a variation in the GP1BA gene, characterized by macrothrombocytopenia, reduced or absent expression of the GPIb-IX-V complex, and lifelong mucocutaneous bleeding. Affected individuals have large platelets with defective ristocetin-induced agglutination, reflecting the absence or dysfunction of GPIbα on the platelet surface. Variants in GP1BA impair production, trafficking, or incorporation of GPIbα into the receptor complex, preventing normal surface assembly and leading to the classic BSS adhesion defect. | | MONDO:1060239 | GP1BB-related Bernard-Soulier syndrome | Any Bernard-Soulier syndrome caused by deficiency or dysfunction of GPIbβ, leading to markedly decreased GPIb-IX-V surface expression and impaired platelet adhesion. Platelets are enlarged and poorly responsive to ristocetin, consistent with severe reduction of the assembled receptor complex. Variants in GP1BB affect production or proper folding of the GPIbβ subunit, preventing formation of the full receptor complex and resulting in the characteristic Bernard-Soulier phenotype. | | MONDO:1060240 | AARS2-related disorder | Any disease in which the cause of the disease is a variation in the AARS2 gene. | | MONDO:1060241 | EDA-related ectodermal dysplasia | Any ectodermal dysplasia syndrome in which the cause of the disease is a variation in the EDA gene. Key features are hypohidrosis and hypotrichosis; the condition is also characterized by skin anomalies such as soft, thin, and dry skin, eczema, and pigmentation anomalies, as well as fine or brittle hair, dental anomalies such as hypodontia or oligodontia, vocal hoarseness, and hyperthermia susceptibility. | | MONDO:1060243 | THG1L-related disorder | Any hereditary disease in which the cause of the disease is a biallelic variation in the THG1L gene, encompassing a phenotypic spectrum that ranges from mild cerebellar ataxia with developmental delay to severe epileptic encephalopathy. | | MONDO:1060244 | THG1L-related epileptic encephalopathy | Any genetic developmental and epileptic encephalopathy in which the cause of the disease is a biallelic variation in the THG1L gene, characterized by profound developmental delay, microcephaly, intractable epilepsy, and cerebellar hypoplasia. | | MONDO:1060245 | SCN2A-related disorder | Any nervous system disorder in which the cause of the disease is a variation in the SCN2A gene, which encodes the Nav1.2 sodium channel critical for neuronal function. SCN2A-related disorders span a broad phenotypic spectrum, from self-limited familial neonatal-infantile epilepsy through severe early-onset epileptic encephalopathies to later-onset epilepsy, autism spectrum disorder and intellectual disability without seizures, and episodic ataxia. Because Nav1.2 is essential for brain development as well as neuronal excitability, the presentation is predominantly neurodevelopmental where developmental delay, intellectual disability, and autism spectrum disorder are the most consistent features across the spectrum, present even in the absence of seizures. Clinical severity is broadly associated with the functional effect of the variant on the Nav1.2 channel, with gain-of-function changes typically linked to early severe epilepsy and loss-of-function changes more often associated with autism spectrum disorder and intellectual disability or intellectual disability, although these relationships are complex and not fully understood. | | MONDO:1060246 | EIF2B1-related permanent neonatal diabetes with transient liver dysfunction | Any permanent neonatal diabetes mellitus in which the cause of the disease is a mutation in the EIF2B1 gene, often accompanied by transient liver dysfunction. |

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<details> <summary>Terms renamed (excluding obsoleted terms): 15</summary>

| Mondo ID | Old Label | New Label | |:---|:---|:---| | MONDO:0001315 | neurocirculatory asthenia | orthostatic intolerance | | MONDO:0008006 | Mobius syndrome | Moebius syndrome | | MONDO:0013722 | hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism | leukodystrophy, hypomyelinating, 8, with or without oligodontia and/or hypogonadotropic hypogonadism | | MONDO:0009843 | hypomyelinating leukodystrophy 3 | leukodystrophy, hypomyelinating, 3 | | MONDO:0011479 | postural orthostatic tachycardia syndrome | postural orthostatic tachycardia syndrome due to NET deficiency | | MONDO:0012125 | hypomyelinating leukodystrophy 2 | leukodystrophy, hypomyelinating, 2 | | MONDO:0012514 | hypomyelinating leukodystrophy 5 | leukodystrophy, hypomyelinating, 5 | | MONDO:0012824 | hypomyelinating leukodystrophy 4 | leukodystrophy, hypomyelinating, 4 | | MONDO:0012905 | hypomyelinating leukodystrophy 6 | leukodystrophy, hypomyelinating, 6 | | MONDO:0014506 | hypomyelinating leukodystrophy 9 | leukodystrophy, hypomyelinating, 9 | | MONDO:0014632 | hypomyelinating leukodystrophy 10 | leukodystrophy, hypomyelinating, 10 | | MONDO:0014666 | hypomyelinating leukodystrophy 11 | leukodystrophy, hypomyelinating, 11 | | MONDO:0014732 | hypomyelinating leukodystrophy 12 | leukodystrophy, hypomyelinating, 12 | | MONDO:0014813 | hypomyelinating leukodystrophy 13 | leukodystrophy, hypomyelinating, 13 | | MONDO:0030714 | osteogenesis imperfecta, IIA 22 | osteogenesis imperfecta, type XXII |

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<details> <summary>Text definitions added to existing terms: 4</summary>

| Mondo ID | Label | New Text Definition | |:---|:---|:---| | MONDO:0010120 | thrombocytopenia 3 | An inherited thrombocytopenia caused by a variation in the FYB1 gene, characterized by small-platelet thrombocytopenia beginning in infancy, with variable mucocutaneous bleeding including petechiae, epistaxis, and heavy menstrual bleeding. Platelet studies in affected individuals reveal reduced pseudopodia formation, impaired integrin activation, increased basal P-selectin and PAC-1 expression, and reduced ability to upregulate activation markers following ADP stimulation. Megakaryocyte abnormalities, including reduced numbers of mature multilobulated megakaryocytes and impaired proplatelet development, reflect a defect in cytoskeletal organization linked to the loss of FYB1's adaptor function in integrin-mediated signaling. | | MONDO:0958325 | thrombocytopenia 12 with or without myopathy | An inherited thrombocytopenia caused by a variation in the GNE gene, characterized by reduced platelet count, enlarged platelets, and a bleeding tendency, with onset in childhood or early adulthood. Clinical studies describe abnormal megakaryocyte maturation and a defect in platelet surface sialylation, resulting from impaired activity of the bifunctional GNE enzyme responsible for the initial steps of sialic-acid biosynthesis. Additional work in patient-derived cells shows altered GNE protein expression and reduced surface sialylation, leading to defective proplatelet formation and shortened platelet survival. | | MONDO:0014837 | thrombocytopenia 6 | A syndromic constitutional thrombocytopenia caused by a variation in the SRC gene, characterized by congenital thrombocytopenia, small platelets, and an increased bleeding tendency beginning in infancy or childhood. Affected individuals show impaired megakaryocyte maturation, reduced proplatelet formation, and altered cytoskeletal organization in patient-derived megakaryocytes, consistent with dysregulated SRC kinase signaling. Platelet function studies show variable but generally mild platelet defects, with bleeding phenotypes ranging from easy bruising to mucocutaneous bleeding. | | MONDO:0032923 | spinocerebellar ataxia, autosomal recessive 28 | Any autosomal recessive cerebellar ataxia in which the cause of the disease is a variation in the THG1L gene, characterized by onset in early childhood of mildly delayed motor development, gait ataxia, incoordination of fine motor movements, and dysarthria. Affected individuals may have features of spasticity and may show mildly impaired cognitive function. Brain imaging shows cerebellar vermis hypoplasia. |

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<details> <summary>Text definitions changed: 16</summary>

| Mondo ID | Label | Old Text Definition | New Text Definition | |:---|:---|:---|:---| | MONDO:0001315 | orthostatic intolerance | A clinical syndrome characterized by palpitation, shortness of breath, labored breathing, subjective complaints of effort and discomfort, all following slight physical exertion. Other symptoms may be dizziness, tremulousness, sweating, and insomnia. Neurocirculatory asthenia is most typically seen as a form of anxiety disorder. | A chronic disorder of dysautonomia, characterized by palpitation, shortness of breath, labored breathing, and subjective complaints of effort and discomfort provoked by physical exertion or upright posture, often accompanied by dizziness, tremulousness, sweating, and insomnia. The heart rate increases by at least 30 beats per minute when moving from a recumbent to a standing position (or ≥40 bpm in individuals 12-19 years of age), without orthostatic hypotension. Historically described as soldier's heart, irritable heart, effort syndrome, or Da Costa syndrome. Anxiety is a frequently associated feature rather than the underlying cause. | | MONDO:0019056 | neuromuscular disease | Any disease that impairs the functioning of the muscles, either directly, being pathologies of the voluntary muscle, or indirectly, being pathologies of nerves or neuromuscular junctions | Any disease that impairs the functioning of the muscles, either directly, being pathologies of the voluntary muscle, or indirectly, being pathologies of nerves or neuromuscular junctions. | | MONDO:0007686 | gray platelet syndrome | Gray platelet syndrome (GPS) is a rare inherited bleeding disorder characterized by macrothrombocytopenia, myelofibrosis, splenomegaly and typical gray appearance of platelets on Wright stained peripheral blood smear. | A rare inherited bleeding disorder caused by a variation in the NBEAL2 gene, characterized by macrothrombocytopenia, myelofibrosis, splenomegaly and typical gray appearance of platelets on Wright stained peripheral blood smear. | | MONDO:1010154 | adult hypophosphatasia | Adult hypophosphatasia (A-HPP) is a mildform of hypophosphatasia characterized by osteomalacia, chondrocalcinosis, osteoarthropathy, stress fractures duringmiddle age, and dental anomalies. | A moderate form of hypophosphatasia characterized by adult onset osteomalacia, chondrocalcinosis, osteoarthropathy, stress fractures , and dental anomalies. | | MONDO:0008332 | platelet-type von Willebrand disease | A bleeding disorder characterized by mild to moderate mucocutaneous bleeding, which becomes more pronounced during pregnancy or following ingestion of drugs that have anti-platelet activity. PT-VWD is due to hyperresponsive platelets, resulting in thrombocytopenia. | A bleeding disorder caused by a variation in the GP1BA gene that increases the affinity of platelet GPIbα for von Willebrand factor (vWF), characterized by mild to moderate mucocutaneous bleeding, which becomes more pronounced during pregnancy or following ingestion of drugs that have anti-platelet activity. PT-VWD is due to hyperresponsive platelets, resulting in thrombocytopenia. Diagnostic laboratory findings include enhanced ristocetin‑induced agglutination and features that mimic type 2B VWD despite a primary platelet defect. Functional studies in human platelets demonstrate abnormally increased vWF binding and hyperresponsiveness, consistent with enhanced GPIbα‑vWF interactions described in patient cells. | | MONDO:0008006 | Moebius syndrome | Moebius syndrome is a very rare congenital cranial dysinnervation disorder characterized by complete or incomplete facial paralysis in association with bilateral palsy of the abducens nerve causing impairment of ocular abduction. The syndrome also includes various other congenital anomalies. | A very rare congenital cranial dysinnervation disorder characterized by unilateral or bilateral non progressive congenital facial palsy (VII cranial nerve) with impairments of ocular abduction (VI cranial nerve). It can also be associated with other cranial nerves palsies, orofacial anomalies and limb defects. | | MONDO:0008553 | platelet-type bleeding disorder 17 | An autosomal dominant condition caused by mutation(s) in the GFI1B gene, encoding zinc finger protein Gfi-1b. It is characterized by a tendency for increased bleeding due to abnormal platelet function. | A platelet type bleeding disorder caused by mutation(s) in the GFI1B gene, encoding zinc finger protein Gfi-1b. It is characterized by a reduction in platelet count, often accompanied by enlarged platelets and abnormalities in α-granule formation, platelet surface CD34 expression, and variable defects in platelet aggregation that together produce a mild to moderate bleeding tendency. | | MONDO:0008555 | thrombocytopenia 2 | An autosomal dominant disorder caused by mutation(s) in the ANKRD26 gene, encoding ANKRD26 protein. Additionally, in one family, a mutation(s) has been identified in the MASTL gene, encoding serine/threonine-protein kinase greatwall. The condition is characterized by mild to moderate bruisability. | An autosomal dominant thrombocytopenia caused by mutation(s) in the ANKRD26 gene, encoding ANKRD26 protein. Additionally, in one family, a mutation(s) has been identified in the MASTL gene, encoding serine/threonine-protein kinase greatwall. The condition is characterized by mild to moderate bruisability, mild to moderate reductions in platelet count, platelets that are generally normal in size, and a mild mucocutaneous bleeding tendency. Individuals show normal platelet ultrastructure and typically have no associated syndromic abnormalities, but megakaryocyte maturation is abnormal, reflecting dysregulated thrombopoiesis. Pathogenic variants occur exclusively in the 5' untranslated region (5'UTR) of ANKRD26, and variants cause gain-of-function overexpression during megakaryopoiesis, disrupting normal signaling and impairing proplatelet formation. | | MONDO:0009279 | triple-A syndrome | Triple A syndrome is a very rare multisystem disease characterized by adrenal insufficiency with isolated glucocorticoid deficiency, achalasia, alacrima, autonomic dysfunction and neurodegeneration. | A very rare multisystem disease characterized by adrenal insufficiency with isolated glucocorticoid deficiency, achalasia, alacrima, autonomic dysfunction and neurodegeneration. | | MONDO:0011136 | Quebec platelet disorder | Quebec platelet syndrome (QPS) is a platelet granule disorder characterized by moderate to severe bleeding after trauma, surgery or obstetric interventions, frequent ecchymoses, mucocutaneous bleeding and muscle and joint bleeds. | A platelet granule disorder caused by a variation in the PLAU gene, characterized by moderate to severe bleeding after trauma, surgery or obstetric interventions, frequent ecchymoses, mucocutaneous bleeding and muscle and joint bleeds. | | MONDO:0011479 | postural orthostatic tachycardia syndrome due to NET deficiency | A condition characterized by development of symptoms while standing. It is an autonomic nervous system disorder and the symptoms are relieved once the person sits back down. Symptoms include heart. | A rare, genetic, primary orthostatic disorder caused by the impaired clearance of neurotransmitters at the synaptic cleft due to the deficiency of norepinephrine transporters (NET), characterized by dizziness, palpitations, fatigue, blurred vision and tachycardia following postural change from a supine to an upright position, in the absence of hypotension. A syncope with transient cognitive impairment and dyspnea may also occur. The norepinephrine transporter deficiency leads to abnormal uptake and high plasma concentrations of norepinephrine. | | MONDO:0012354 | platelet-type bleeding disorder 8 | P2Y12 defect is a rare hemorrhagic disorder characterized by mild to moderate bleeding diathesis with easy bruising, mucosal bleedings, and excessive post-operative hemorrhage due to defect of the platelet P2Y12 receptor resulting in selective impairment of platelet responses to adenosine diphosphate. | A platelet type bleeding disorder of autosomal recessive inheritance caused by a variation in the P2RY12 gene, characterized by mild to moderate bleeding diathesis with easy bruising, mucosal bleedings, and excessive post-operative hemorrhage due to defect of the platelet P2Y12 receptor resulting in selective impairment of platelet responses to adenosine diphosphate. | | MONDO:0014078 | platelet-type bleeding disorder 15 | Any inherited bleeding disorder, platelet-type in which the cause of the disease is a mutation in the ACTN1 gene. | Any inherited bleeding disorder, platelet-type in which the cause of the disease is a mutation in the ACTN1 gene, characterized by mild thrombocytopenia, enlarged platelets, and platelet anisocytosis, with most individuals exhibiting no bleeding or only mild epistaxis. Human platelet studies show normal aggregation, clot retraction, and spreading, indicating that bleeding symptoms arise from reduced platelet mass rather than functional defects. Missense variants in ACTN1 disrupt actin-filament organization in megakaryocytes, producing fewer and larger proplatelet tips and resulting in macrothrombocytopenia. | | MONDO:0014830 | platelet-type bleeding disorder 20 | Any inherited bleeding disorder, platelet-type in which the cause of the disease is a mutation in the SLFN14 gene. | Any inherited bleeding disorder, platelet-type in which the cause of the disease is a mutation in the SLFN14 gene, characterized by moderate thrombocytopenia, enlarged platelets in some individuals, and a mucocutaneous bleeding diathesis including bruising, epistaxis, gum bleeding, menorrhagia, and postpartum hemorrhage. Human platelet studies consistently show reduced aggregation in response to ADP, collagen, and PAR-1, accompanied by decreased ATP secretion and markedly reduced dense-granule numbers, indicating a secretion defect. SLFN14 missense variants impair protein stability and disrupt ribosomal RNA-regulatory pathways in megakaryocytes, leading to defective proplatelet formation, impaired megakaryocyte maturation, and reduced platelet output. | | MONDO:0014970 | spermatogenic failure 17 | Any azoospermia in which the cause of the disease is a mutation in the PLCZ1 gene. | Any spermatogenic failure in which the cause of the disease is a mutation in the PLCZ1 gene. It is a male infertility due to acrosomal defects that lead to oocyte activation deficiency and total fertilization failure | | MONDO:0800047 | macrothrombocytopenia, isolated, 1, autosomal dominant | Any autosomal dominant macrothrombocytopenia in which the cause of the disease is a mutation in the TUBB1 gene. | Any autosomal dominant macrothrombocytopenia in which the cause of the disease is a mutation in the TUBB1 gene, characterized by mild to moderate thrombocytopenia with large platelets and normal or near-normal bleeding symptoms. Structural studies in patient platelets show disorganized or reduced beta1-tubulin staining and abnormal marginal microtubule bands, impairing proplatelet formation and leading to fewer, larger circulating platelets. Functional platelet assays in affected individuals typically show qualitatively normal aggregation, with the clinical phenotype driven primarily by reduced platelet number rather than intrinsic platelet-function defects. |

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

| Mondo ID | Label | Replacement | |:---|:---|:---| | MONDO:0600011 | obsolete mild hypophosphatasia | adult hypophosphatasia (MONDO:1010154) | | MONDO:0971094 | obsolete cardiac anomalies-short stature-joint hypermobility-facial dysmorphism syndrome due to TAB2 mutation | congenital heart defects, multiple types, 2 (MONDO:0014000) |

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<details> <summary>Terms obsoleted without replacement: 1</summary>

| Mondo ID | Label | |:---|:---| | MONDO:0021834 | obsolete Akaba Hayasaka syndrome |

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<details> <summary>New obsoletion candidates: 4</summary>

| Mondo ID | Label | |:---|:---| | MONDO:0004466 | neuronitis | | MONDO:0004910 | mitral valve prolapse | | MONDO:0035437 | CEBPE-associated autoinflammation-immunodeficiency-neutrophil dysfunction syndrome | | MONDO:0979233 | immunodysregulation with variable immunodeficiency and autoimmunity |

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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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