Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency(GPIBD1)

MedGen UID:: 1684821
•Concept ID:: C5201145
•: Disease or Syndrome

Synonyms:	GLYCOSYLPHOSPHATIDYLINOSITOL BIOSYNTHESIS DEFECT 1; Glycosylphosphatidylinositol deficiency; GPI deficiency; GPIBD1
Modes of inheritance:	Autosomal recessive inheritance MedGen UID: 141025 •Concept ID: C0441748 • Intellectual Product Source: Orphanet A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). Autosomal recessive inheritance (Orphanet)

Gene (location): Gene(s) directly associated with this condition or phenotype.	PIGM (1q23.2)

Monarch Initiative:	MONDO:0012465
OMIM®:	610293
Orphanet:	ORPHA83639

Definition

Glycosylphosphatidylinositol is a glycolipid that anchors more than 150 proteins to the cell surface, and these proteins, termed GPI-anchored proteins (GPI-APs), perform a variety of functions as enzymes, adhesion molecules, complement regulators, and coreceptors in signal transduction pathways. Reduced surface levels of GPI-APs or abnormal GPI-AP structure can therefore result in variable manifestations. Glycosylphosphatidylinositol biosynthesis defect-1 (GPIBD1) is characterized predominantly by portal hypertension due to portal vein thrombosis. Most patients have absence seizures, cerebral thrombosis, and macrocephaly. Some patients have mildly to moderately impaired intellectual development (summary by Makrythanasis et al., 2016; Pode-Shakked et al., 2019). Genetic Heterogeneity of Glycosylphosphatidylinositol Biosynthesis Defects Also see GPIBD2 (239300), caused by mutation in the PIGV gene (610274); GPIBD3 (614080), caused by mutation in the PIGN gene (606097); GPIBD4 (300868), caused by mutation in the PIGA gene (311770); GPIBD5 (280000), caused by mutation in the PIGL gene (605947); GPIBD6 (614749), caused by mutation in the PIGO gene (614730); GPIBD7 (615398), caused by mutation in the PIGT gene (610272); GPIBD8 (614207), caused by mutation in the PGAP2 gene (615187); GPIBD9 (615802), caused by mutation in the PGAP1 gene (611655); GPIBD10 (615716), caused by mutation in the PGAP3 gene (611801); GPIBD11 (616025), caused by mutation in the PIGW gene (610275); GPIBD12 (616809), caused by mutation in the PIGY gene (610662); GPIBD13 (616917), caused by mutation in the PIGG gene (616918); GPIBD14 (617599), caused by mutation in the PIGP gene (605938); GPIBD15 (617810), caused by mutation in the GPAA1 gene (603048); GPIBD16 (617816), caused by mutation in the PIGC gene (601730); GPIBD17 (618010), caused by mutation in the PIGH gene (600154); GPIBD18 (618143), caused by mutation in the PIGS gene (610271); GPIBD19 (618548), caused by mutation in the PIGQ gene (605754); GPIBD20 (618580), caused by mutation in the PIGB gene (604122); GPIBD21 (618590), caused by mutation in the PIGU gene (608528); GPIBD22 (618879), caused by mutation in the PIGK gene (605087); GPIBD23 (617020), caused by mutation in the ARV1 gene (611647); GPIBD24 (619356), caused by mutation in the PIGF gene (600153); and GPIBD25 (619985), caused by mutation in the C18ORF32 gene (619979). [from OMIM]

Clinical features

From HPO

Portal hypertension

MedGen UID:: 9375
•Concept ID:: C0020541
•: Disease or Syndrome

Increased pressure in the portal vein.

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Hepatomegaly

MedGen UID:: 42428
•Concept ID:: C0019209
•: Finding

Abnormally increased size of the liver.

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Portal vein thrombosis

MedGen UID:: 56372
•Concept ID:: C0155773
•: Disease or Syndrome

Thrombosis of the portal vein and/or its tributaries, which include the splenic vein and the superior and inferior mesenteric veins.

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Atonic seizure

MedGen UID:: 78735
•Concept ID:: C0270846
•: Disease or Syndrome

Atonic seizure is a type of motor seizure characterized by a sudden loss or diminution of muscle tone without apparent preceding myoclonic or tonic event lasting about 1 to 2 seconds, involving head, trunk, jaw, or limb musculature.

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Delayed speech and language development

MedGen UID:: 105318
•Concept ID:: C0454644
•: Finding

A degree of language development that is significantly below the norm for a child of a specified age.

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Generalized non-motor (absence) seizure

MedGen UID:: 1385688
•Concept ID:: C4316903
•: Disease or Syndrome

A generalized non-motor (absence) seizure is a type of a type of dialeptic seizure that is of electrographically generalized onset. It is a generalized seizure characterized by an interruption of activities, a blank stare, and usually the person will be unresponsive when spoken to. Any ictal motor phenomena are minor in comparison to these non-motor features.

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Hepatic vein thrombosis

MedGen UID:: 9217
•Concept ID:: C0019154
•: Disease or Syndrome

An obstruction in the veins of the liver caused by a blood clot (thrombosis).

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Venous thrombosis

MedGen UID:: 22631
•Concept ID:: C0042487
•: Pathologic Function

Thrombophilia is a multifactorial disorder of inappropriate clot formation resulting from an interaction of genetic, acquired, and circumstantial predisposing factors. Venous thromboembolism most commonly manifests as deep vein thrombosis, which may progress to pulmonary embolism if the clot dislodges and travels to the lung. Other manifestations include thromboses of the cerebral or visceral veins and recurrent pregnancy loss (summary by Seligsohn and Lubetsky, 2001 and Varga and Kujovich, 2012). Genetic Heterogeneity of Thrombophilia THPH2 (188055) is caused by mutation in the F5 gene (612309) on chromosome 1q23; THPH3 (176860) and THPH4 (612304) are both caused by mutation in the PROC gene (612283) on 2q; THPH5 (612336) and THPH6 (614514) are caused by mutation in the PROS1 gene (176880) on 3q11; THPH7 (613118) is caused by mutation in the AT3 gene (107300) on 1q25; THPH8 (300807) is caused by mutation in the F9 gene (300746) on Xq27; THPH9 (612348) is associated with decreased release of tissue plasminogen activator (PLAT; 173370); THPH10 (612356) is caused by mutation in the HCF2 gene (142360) on 22q11; THPH11 (613116) is caused by mutation in the HRG gene (142640) on 3q27; and THPH12 (614486) is associated with variation in the THBD gene (188040) on 20p11. Susceptibility to thrombosis has also been associated with variation in additional genes, including MTHFR (607093.0003); F13B (134580.0003); plasminogen activator inhibitor (SERPINE1; 173360); and several genes encoding fibrinogen (FGA, 134820; FGB, 134830; FGG, 134850). Variation in the SERPINA10 (see 605271.0001), KNG1 (612358) and HABP2 (603924) genes has also been reported. Protection against venous thrombosis is associated with variation in the F13A1 gene (134570) on 6p25.

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Abnormal bone marrow cell morphology