- Reduced factor XII activity (HP:0004841): Decreased activity of coagulation factor XII. Factor XII (fXII) is part of the intrinsic coagulation pathway and binds to exposed collagen at site of vessel wall injury, activated by high-MW kininogen and kallikrein, thereby initiating the coagulation cascade. Evidence: PCS. Frequency: 1/1. (PMID:32884905)
- Strabismus (HP:0000486): A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error. Evidence: PCS. Frequency: 1/1. (PMID:32884905)
- Middle age onset (HP:0003596): A type of adult onset with onset of symptoms at the age of 40 to 60 years. Evidence: PCS. Frequency: 1/7. (PMID:33964207)
- Reduced factor IX activity (HP:0011858): Decreased activity of coagulation factor IX. Factor IX, which itself is activated by factor Xa or factor VIIa to form factor IXa, activates factor X into factor Xa. Evidence: PCS. Frequency: 4/6. (PMID:33964207)
- Elevated circulating alkaline phosphatase concentration (HP:0003155): Abnormally increased serum levels of alkaline phosphatase activity. Evidence: PCS. Frequency: 1/1. (PMID:32884905)
- Hypotonia (HP:0001252): Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist. Evidence: PCS. Frequency: 1/1. (PMID:32884905)
- Gastroesophageal reflux (HP:0002020): A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter. Evidence: PCS. Frequency: 1/1. (PMID:32884905)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 3/8. (PMID:33728255;PMID:33964207)
- Type II transferrin isoform profile (HP:0012301): Abnormal transferrin isoform profile consistent with a type II congenital disorder of glycosylation. Evidence: PCS. Frequency: 9/9. (PMID:32884905;PMID:33728255;PMID:33964207)
- Type I diabetes mellitus (HP:0100651): A chronic condition in which the pancreas produces little or no insulin. Type I diabetes mellitus is manifested by the sudden onset of severe hyperglycemia with rapid progression to diabetic ketoacidosis unless treated with insulin. Evidence: PCS. Frequency: 1/1. (PMID:33728255)
- Abnormal protein N-linked glycosylation (HP:0012347): An anomaly of protein N-linked glycosylation, i.e., an abnormality of the protein glycosylation process in which a carbohydrate or carbohydrate derivative unit is added to a protein via a nitrogen atom in an amino acid residue in a protein. Evidence: PCS. Frequency: 7/7. (PMID:33964207)
- Moderate albuminuria (HP:0012594): The presence of moderately increased concentrations of albumin in the urine, defined as and albumin-creatinine ratio (ACR) of 30 to 299 mg/gm (3.4 to 34 mg/mmol). Evidence: PCS. Frequency: 1/1. (PMID:33728255)
- Reduced factor XI activity (HP:0001929): Decreased activity of coagulation factor XI. Factor XI, also known as plasma thromboplastin antecedent, is a serine proteinase that activates factor IX. Evidence: PCS. Frequency: 6/6. (PMID:33964207)
- Bile duct proliferation (HP:0001408): Proliferative changes of the bile ducts. Evidence: PCS. Frequency: 1/1. (PMID:33728255)
- Ankyloglossia (HP:0010296): Short or anteriorly attached lingual frenulum, associated with limited mobility of the tongue. Evidence: PCS. Frequency: 2/8. (PMID:32884905;PMID:33964207)
- Young adult onset (HP:0011462): Onset of disease at the age of between 16 and 40 years. Evidence: PCS. Frequency: 1/7. (PMID:33964207)
- Hypertelorism (HP:0000316): Interpupillary distance more than 2 SD above the mean (alternatively, the appearance of an increased interpupillary distance or widely spaced eyes). Evidence: PCS. Frequency: 1/1. (PMID:33728255)
- Pes planus (HP:0001763): A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced. Evidence: PCS. Frequency: 1/1. (PMID:32884905)
- Elevated circulating aspartate aminotransferase concentration (HP:0031956): The concentration of aspartate aminotransferase (AST) in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 8/8. (PMID:32884905;PMID:33728255;PMID:33964207)
- Elevated gamma-glutamyltransferase level (HP:0030948): Increased level of the enzyme gamma-glutamyltransferase (GGT). GGT is mainly present in kidney, liver, and pancreatic cells, but small amounts are present in other tissues. Evidence: PCS. Frequency: 1/1. (PMID:32884905)
- Bleeding with minor or no trauma (HP:0011889): Significant bleeding or hemorrhage without significant precipitating factor. Evidence: PCS. Frequency: 1/1. (PMID:33728255)
- Microscopic hematuria (HP:0002907): Microscopic hematuria detected by dipstick or microscopic examination of the urine. Evidence: PCS. Frequency: 1/1. (PMID:33728255)
- Reduced factor VII activity (HP:0008169): Reduced activity of coagulation factor VII. Factor VII is part of the extrinsic coagulation pathway, which is initiated at the site of injury in response to the release of tissue factor (fIII). Tissue factor and activated factor VII catalyze the activation of factor X. Evidence: PCS. Frequency: 1/1. (PMID:32884905)
- Pectus excavatum (HP:0000767): A defect of the chest wall characterized by a depression of the sternum, giving the chest ("pectus") a caved-in ("excavatum") appearance. Evidence: PCS. Frequency: 1/1. (PMID:33728255)
- Reduced antithrombin III activity (HP:0001976): An abnormality of coagulation related to a decreased concentration of antithrombin-III. Evidence: PCS. Frequency: 1/1. (PMID:32884905)
- Recurrent otitis media (HP:0000403): Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media. Evidence: PCS. Frequency: 1/1. (PMID:33728255)
- Microcytic anemia (HP:0001935): A kind of anemia in which the volume of the red blood cells is reduced. Evidence: PCS. Frequency: 1/1. (PMID:33728255)
- Pectus carinatum (HP:0000768): A deformity of the chest caused by overgrowth of the ribs and characterized by protrusion of the sternum. Evidence: PCS. Frequency: 1/1. (PMID:32884905)
- Autosomal dominant inheritance (HP:0000006): 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 heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele. Evidence: PCS. (PMID:32884905)
- Low-set ears (HP:0000369): Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear. Evidence: PCS. Frequency: 1/1. (PMID:32884905)
- Facial asymmetry (HP:0000324): An abnormal difference between the left and right sides of the face. Evidence: PCS. Frequency: 1/1. (PMID:32884905)
- Wide nose (HP:0000445): Interalar distance more than two standard deviations above the mean for age, i.e., an apparently increased width of the nasal base and alae. Evidence: PCS. Frequency: 1/1. (PMID:32884905)
- Hepatic steatosis (HP:0001397): Steatosis is a term used to denote lipid accumulation within hepatocytes. Evidence: PCS. Frequency: 1/1. (PMID:32884905)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. Frequency: 1/1. (PMID:32884905)
- Inguinal hernia (HP:0000023): Protrusion of the contents of the abdominal cavity through the inguinal canal. Evidence: PCS. Frequency: 1/1. (PMID:32884905)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: PCS. Frequency: 1/1. (PMID:33728255)
- Elevated circulating alanine aminotransferase concentration (HP:0031964): An abnormally high concentration in the circulation of alanine aminotransferase (ALT). Evidence: PCS. Frequency: 2/2. (PMID:32884905;PMID:33728255)
- Osteoporosis (HP:0000939): Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD). Evidence: PCS. Frequency: 1/1. (PMID:32884905)
- Prolonged prothrombin time (HP:0008151): Increased time to coagulation in the prothrombin time test, which is a measure of the extrinsic pathway of coagulation. The results of the prothrombin time test are often expressed in terms of the International normalized ratio (INR), which is calculated as a ratio of the patient's prothrombin time (PT) to a control PT standardized for the potency of the thromboplastin reagent developed by the World Health Organization (WHO) using the formula: INR is equal to Patient PT divided by Control PT. Evidence: PCS. Frequency: 2/2. (PMID:32884905;PMID:33728255)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 1/1. (PMID:32884905)
- Ventricular septal defect (HP:0001629): A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum. Evidence: PCS. Frequency: 2/7. (PMID:33964207)
- Anemia (HP:0001903): A reduction in erythrocytes volume or hemoglobin concentration. Evidence: PCS. Frequency: 1/1. (PMID:32884905)
- Concave nasal ridge (HP:0011120): Nasal ridge curving posteriorly to an imaginary line that connects the nasal root and tip. Evidence: PCS. Frequency: 1/1. (PMID:33728255)
- Reduced factor XIII activity (HP:0008357): Decreased activity of coagulation factor XIII (also known as fibrin stabilizing factor). Activated Factor XIII cross-links fibrin polymers solidifying the clot. Evidence: PCS. Frequency: 1/1. (PMID:32884905)
- Narrow chest (HP:0000774): Reduced width of the chest from side to side, associated with a reduced distance from the sternal notch to the tip of the shoulder. Evidence: PCS. Frequency: 1/1. (PMID:32884905)
- Elevated circulating hepatic transaminase concentration (HP:0002910): Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage. Evidence: PCS. Frequency: 1/1. (PMID:33728255)
- Prolonged neonatal jaundice (HP:0006579): Neonatal jaundice refers to a yellowing of the skin and other tissues of a newborn infant as a result of increased concentrations of bilirubin in the blood. Neonatal jaundice affects over half of all newborns to some extent in the first week of life. Prolonged neonatal jaundice is said to be present if the jaundice persists for longer than 14 days in term infants and 21 days in preterm infants. Evidence: PCS. Frequency: 1/1. (PMID:33728255)
- Splenomegaly (HP:0001744): Abnormal increased size of the spleen. Evidence: PCS. Frequency: 1/1. (PMID:33728255)
- Prolonged partial thromboplastin time (HP:0003645): Increased time to coagulation in the partial thromboplastin time (PTT) test, a measure of the intrinsic and common coagulation pathways. Phospholipid, and activator, and calcium are mixed into an anticoagulated plasma sample, and the time is measured until a thrombus forms. Evidence: PCS. Frequency: 2/2. (PMID:32884905;PMID:33728255)
- Narrow face (HP:0000275): Bizygomatic (upper face) and bigonial (lower face) width are both more than 2 standard deviations below the mean (objective); or, an apparent reduction in the width of the upper and lower face (subjective). Evidence: PCS. Frequency: 1/1. (PMID:32884905)
- Reduced coagulation factor V activity (HP:0003225): Decreased activity of coagulation factor V. Evidence: PCS. Frequency: 7/8. (PMID:32884905;PMID:33964207)
- Juvenile onset (HP:0003621): Onset of signs or symptoms of disease between the age of 5 and 15 years. Evidence: PCS. Frequency: 3/7. (PMID:33964207)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 4/8. (PMID:33728255;PMID:33964207)
- Delayed ability to walk (HP:0031936): A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months. Evidence: PCS. Frequency: 1/1. (PMID:32884905)
- Vomiting (HP:0002013): Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions. Evidence: PCS. Frequency: 1/1. (PMID:33728255)
- Membranoproliferative glomerulonephritis (HP:0000793): A type of glomerulonephritis characterized by diffuse mesangial cell proliferation and the thickening of capillary walls due to subendothelial extension of the mesangium. The term membranoproliferative glomerulonephritis is often employed to denote a general pattern of glomerular injury seen in a variety of disease processes that share a common pathogenetic mechanism, rather than to describe a single disease entity. Evidence: PCS. Frequency: 1/1. (PMID:33728255)
- Underdeveloped nasal alae (HP:0000430): Thinned, deficient, or excessively arched ala nasi. Evidence: PCS. Frequency: 1/1. (PMID:33728255)
- Hypofibrinogenemia (HP:0011900): Decreased concentration of fibrinogen in the blood. Evidence: PCS. Frequency: 2/2. (PMID:32884905;PMID:33728255)
- Supernumerary tooth (HP:0011069): The presence of one or more teeth additional to the normal number. Evidence: PCS. Frequency: 1/1. (PMID:32884905)
- Abnormal protein O-linked glycosylation (HP:0012358): An anomaly of protein O-linked glycosylation, i.e., of the process in which a carbohydrate or carbohydrate derivative unit is added to a protein via the hydroxyl group of a serine or threonine residue. Evidence: PCS. Frequency: 7/7. (PMID:33964207)
- Increased hepatic echogenicity (HP:0031141): Increased echogenicity of liver tissue on sonography, manifested as an increased amount of white on the screen of the sonography device. Evidence: PCS. Frequency: 1/1. (PMID:32884905)
- Tetralogy of Fallot (HP:0001636): A congenital cardiac malformation comprising pulmonary stenosis, overriding aorta, ventricular septum defect, and right ventricular hypertrophy. The diagnosis of TOF is made if at least three of the four above mentioned features are present. Evidence: PCS. Frequency: 1/7. (PMID:33964207)
- Pointed chin (HP:0000307): A marked tapering of the lower face to the chin. Evidence: PCS. Frequency: 1/1. (PMID:33728255)
- Thrombocytopenia (HP:0001873): A reduction in the number of circulating thrombocytes. Evidence: PCS. Frequency: 1/1. (PMID:32884905)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: PCS. Frequency: 1/1. (PMID:32884905)
- Bilateral choanal atresia (HP:0004502): Bilateral absence (atresia) of the posterior nasal aperture (choana). Evidence: PCS. Frequency: 1/1. (PMID:32884905)
These phenotypes are associated with the disease congenital disorder of glycosylation, type IIw (OMIM:619525).