Phenotypes associated with the disease PMM2-CDG (ORPHA:79318):
- Joint hypermobility (HP:0001382): The capability that a joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79318)
- High palate (HP:0000218): Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective). Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:79318)
- 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: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:79318)
- Upslanted palpebral fissure (HP:0000582): The palpebral fissure inclination is more than two standard deviations above the mean for age (objective); or, the inclination of the palpebral fissure is greater than typical for age. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:79318)
- Wide mouth (HP:0000154): Distance between the oral commissures more than 2 SD above the mean. Alternatively, an apparently increased width of the oral aperture (subjective). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79318)
- Thin upper lip vermilion (HP:0000219): Height of the vermilion of the upper lip in the midline more than 2 SD below the mean. Alternatively, an apparently reduced height of the vermilion of the upper lip in the frontal view (subjective). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79318)
- Long face (HP:0000276): Facial height (length) is more than 2 standard deviations above the mean (objective); or, an apparent increase in the height (length) of the face (subjective). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79318)
- Retrognathia (HP:0000278): An abnormality in which the mandible is mislocalised posteriorly. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79318)
- Epicanthus (HP:0000286): A fold of skin starting above the medial aspect of the upper eyelid and arching downward to cover, pass in front of and lateral to the medial canthus. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79318)
- Mandibular prognathia (HP:0000303): Abnormal prominence of the chin related to increased length of the mandible. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79318)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79318)
- Long philtrum (HP:0000343): Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79318)
- Prominent nose (HP:0000448): Distance between subnasale and pronasale more than two standard deviations above the mean, or alternatively, an apparently increased anterior protrusion of the nasal tip. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79318)
- Anteverted nares (HP:0000463): Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79318)
- Esotropia (HP:0000565): A form of strabismus with one or both eyes turned inward ('crossed') to a relatively severe degree, usually defined as 10 diopters or more. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79318)
- Delayed speech and language development (HP:0000750): A degree of language development that is significantly below the norm for a child of a specified age. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79318)
- Osteopenia (HP:0000938): Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79318)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79318)
- Seizure (HP:0001250): A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79318)
- Global developmental delay (HP:0001263): A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79318)
- Hyporeflexia (HP:0001265): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79318)
- Cerebellar hypoplasia (HP:0001321): Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79318)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79318)
- Abnormal facial shape (HP:0001999): An abnormal morphology (form) of the face or its components. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79318)
- Vomiting (HP:0002013): Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79318)
- Kyphoscoliosis (HP:0002751): An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79318)
- Inverted nipples (HP:0003186): The presence of nipples that instead of pointing outward are retracted inwards. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79318)
- Abnormal subcutaneous fat tissue distribution (HP:0007552). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79318)
- Axial hypotonia (HP:0008936): Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79318)
- Lipodystrophy (HP:0009125): Degenerative changes of the fat tissue. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79318)
- Prominent forehead (HP:0011220): Forward prominence of the entire forehead, due to protrusion of the frontal bone. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79318)
- Feeding difficulties (HP:0011968): Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79318)
- Delayed myelination (HP:0012448): Delayed myelination. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79318)
- Long fingers (HP:0100807): The middle finger is more than 2 SD above the mean for newborns 27 to 41 weeks EGA or above the 97th centile for children from birth to 16 years of age AND the five digits retain their normal length proportions relative to each other (i.e., it is not the case that the middle finger is the only lengthened digit), or, Fingers that appear disproportionately long compared to the palm of the hand. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:79318)
- Hypogonadotropic hypogonadism (HP:0000044): Hypogonadotropic hypogonadism is characterized by reduced function of the gonads (testes in males or ovaries in females) and results from the absence of the gonadal stimulating pituitary hormones: follicle stimulating hormone (FSH) and luteinizing hormone (LH). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Abnormal renal tubule morphology (HP:0000091): An abnormality of the renal tubules. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Proteinuria (HP:0000093): Increased levels of protein in the urine. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Nephrotic syndrome (HP:0000100): Nephrotic syndrome is a collection of findings resulting from glomerular dysfunction with an increase in glomerular capillary wall permeability associated with pronounced proteinuria. Nephrotic syndrome refers to the constellation of clinical findings that result from severe renal loss of protein, with Proteinuria and hypoalbuminemia, edema, and hyperlipidemia. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Abnormal pinna morphology (HP:0000377): An abnormality of the pinna, which is also referred to as the auricle or external ear. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Macrotia (HP:0000400): Median longitudinal ear length greater than two standard deviations above the mean and median ear width greater than two standard deviations above the mean (objective); or, apparent increase in length and width of the pinna (subjective). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Prominent nasal bridge (HP:0000426): Anterior positioning of the nasal root in comparison to the usual positioning for age. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Rod-cone dystrophy (HP:0000510): An inherited retinal disease subtype in which the rod photoreceptors appear to be more severely affected than the cone photoreceptors. Typical presentation is with nyctalopia (due to rod dysfunction) followed by loss of mid-peripheral field of vision, which gradually extends and leaves many patients with a small central island of vision due to the preservation of macular cones. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Cataract (HP:0000518): A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Myopia (HP:0000545): An abnormality of refraction characterized by the ability to see objects nearby clearly, while objects in the distance appear blurry. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Hyperinsulinemia (HP:0000842): An increased concentration of insulin in the blood. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Elevated circulating growth hormone concentration (HP:0000845): Acromegaly is a condition resulting from overproduction of growth hormone by the pituitary gland in persons with closed epiphyses, and consists chiefly in the enlargement of the distal parts of the body. The circumference of the skull increases, the nose becomes broad, the tongue becomes enlarged, the facial features become coarsened, the mandible grows excessively, and the teeth become separated. The fingers and toes grow chiefly in thickness. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Insulin resistance (HP:0000855): Increased resistance towards insulin, that is, diminished effectiveness of insulin in reducing blood glucose levels. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Increased circulating prolactin concentration (HP:0000870): The presence of abnormally increased levels of prolactin in the blood. Prolactin is a peptide hormone produced by the anterior pituitary gland that plays a role in breast development and lactation during pregnancy. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Intellectual disability (HP:0001249): The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Ataxia (HP:0001251): Ataxia refers to impaired coordination of voluntary muscle movement. Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Cerebellar vermis hypoplasia (HP:0001320): Underdevelopment of the vermis of cerebellum. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Hepatic fibrosis (HP:0001395): The presence of excessive fibrous connective tissue in the liver. Fibrosis is a reparative or reactive process. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Pericardial effusion (HP:0001698): Accumulation of fluid within the pericardium. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Fever (HP:0001945): Body temperature elevated above the normal range. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Reduced antithrombin III activity (HP:0001976): An abnormality of coagulation related to a decreased concentration of antithrombin-III. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Respiratory distress (HP:0002098): Respiratory distress is objectively observable as the physical or emotional consequences from the experience of dyspnea. The physical presentation of respiratory distress is generally referred to as labored breathing, while the sensation of respiratory distress is called shortness of breath or dyspnea. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Enlarged cisterna magna (HP:0002280): Increase in size of the cisterna magna, one of three principal openings in the subarachnoid space between the arachnoid and pia mater, located between the cerebellum and the dorsal surface of the medulla oblongata. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Multiple joint contractures (HP:0002828). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Elevated circulating thyroid-stimulating hormone concentration (HP:0002925): Increased concentration of thyroid-stimulating hormone (TSH) in the blood circulation. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Hypoalbuminemia (HP:0003073): The concentration of albumin in the blood circulation is below the lower limit of normal. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Multiple renal cysts (HP:0005562): The presence of many cysts in the kidney. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Decreased testicular size (HP:0008734): Reduced volume of the testicle (the male gonad). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Peripheral neuropathy (HP:0009830): Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Aplasia of the ovary (HP:0010463): Aplasia, that is failure to develop, of the ovary. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Abnormality of coordination (HP:0011443). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Abnormal skeletal morphology (HP:0011842): An abnormality of the form, structure, or size of the skeletal system. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Aspiration pneumonia (HP:0011951): Pneumonia due to the aspiration (breathing in) of food, liquid, or gastric contents into the upper respiratory tract. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Decreased circulating thyroxine-binding globulin concentration (HP:0034591): The concentration of thyroxine-binding globulin in the blood circulation is below the lower limit of normal. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Hyperplastic labia majora (HP:0012882): Overgrowth of the outer labia. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Abnormal liver parenchyma morphology (HP:0030146): A structural anomaly of the liver located predominantly in the hepatocytes as opposed to stromal cells. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Photoreceptor layer loss on macular OCT (HP:0030609): Loss of the outer nuclear layer (photoreceptor layer) as assessed by ocular coherence tomography. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:79318)
- Platyspondyly (HP:0000926): A flattened vertebral body shape with reduced distance between the vertebral endplates. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:79318)
- Lymphedema (HP:0001004): Localized fluid retention and tissue swelling caused by a compromised lymphatic system. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:79318)
- Dandy-Walker malformation (HP:0001305): A congenital brain malformation typically characterized by incomplete formation of the cerebellar vermis, dilation of the fourth ventricle, and enlargement of the posterior fossa. In layman's terms, Dandy Walker malformation is a cyst in the cerebellum (typically symmetrical) that is involved with the fourth ventricle. This may interfere with the ability to drain cerebrospinal fluid from the brain, resulting in hydrocephalus. Dandy Walker cysts are formed during early embryonic development, while the brain forms. The cyst in the cerebellum typically has several blood vessels running through it connecting to the brain, thereby prohibiting surgical removal. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:79318)
- Hypertrophic cardiomyopathy (HP:0001639): Hypertrophic cardiomyopathy (HCM) is defined by the presence of increased ventricular wall thickness or mass in the absence of loading conditions (hypertension, valve disease) sufficient to cause the observed abnormality. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:79318)
- Angina pectoris (HP:0001681): Paroxysmal chest pain that occurs with exertion or stress and is related to myocardial ischemia. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:79318)
- Pericarditis (HP:0001701): Inflammation of the sac-like covering around the heart (pericardium). Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:79318)
- Intracranial hemorrhage (HP:0002170): Hemorrhage occurring within the skull. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:79318)
- Deep venous thrombosis (HP:0002625): Formation of a blot clot in a deep vein. The clot often blocks blood flow, causing swelling and pain. The deep veins of the leg are most often affected. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:79318)
- Anasarca (HP:0012050): An extreme form of generalized edema with widespread and massive edema due to effusion of fluid into the extracellular space. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:79318)
- Impaired antigen-specific response (HP:0031404): An impaired immune response mediated by cells expressing specific receptors for antigen produced through a somatic diversification process, and allowing for an enhanced secondary response to subsequent exposures to the same antigen (immunological memory). Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:79318)
- Impaired neutrophil chemotaxis (HP:0040238): An impairment of the migration of neutrophils towards chemoattractants as part of the innate immune response. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:79318)