Phenotypes associated with the disease neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 2 (OMIM:619418):
- Constriction of peripheral visual field (HP:0001133): An absolute or relative decrease in retinal sensitivity extending from edge (periphery) of the visual field in a concentric pattern. The visual field is the area that is perceived simultaneously by a fixating eye. Evidence: PCS. Frequency: 1/1. (PMID:29232904)
- 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: PCS. Frequency: 1/2. (PMID:27633801)
- Failure to thrive in infancy (HP:0001531). Evidence: PCS. Frequency: 1/2. (PMID:27633801)
- 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: 3/3. (PMID:27633801;PMID:29232904)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: IEA. Frequency: 2/2. (PMID:27633801)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 7/8. (PMID:29232904;PMID:30304524)
- Sepsis (HP:0100806): Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Evidence: PCS. Frequency: 3/7. (PMID:30304524)
- Macular atrophy (HP:0007401): A nonspecific term denoting wasting, especially as a result of degeneration, of the retinal pigment epithelium (RPE) and neurosensory retinal cells in the macula. Evidence: PCS. Frequency: 1/1. (PMID:29232904)
- Cholestatic liver disease (HP:0002611). Evidence: PCS. Frequency: 7/7. (PMID:30304524)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 7/7. (PMID:30304524)
- Expressive language delay (HP:0002474): A delay in the acquisition of the ability to use language to communicate needs, wishes, or thoughts. Evidence: PCS. Frequency: 7/7. (PMID:30304524)
- Hypertriglyceridemia (HP:0002155): An abnormal increase in the level of triglycerides in the blood. Evidence: PCS. Frequency: 2/2. (PMID:27633801)
- Hypoplasia of the corpus callosum (HP:0002079): Underdevelopment of the corpus callosum. Evidence: PCS. Frequency: 2/2. (PMID:27633801)
- Full cheeks (HP:0000293): Increased prominence or roundness of soft tissues between zygomata and mandible. Evidence: PCS. Frequency: 2/2. (PMID:27633801)
- Generalized-onset seizure (HP:0002197): A generalized-onset seizure is a type of seizure originating at some point within, and rapidly engaging, bilaterally distributed networks. The networks may include cortical and subcortical structures but not necessarily the entire cortex. Evidence: PCS. Frequency: 1/1. (PMID:29232904)
- 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: PCS. Frequency: 1/2. (PMID:27633801)
- Deeply set eye (HP:0000490): An eye that is more deeply recessed into the plane of the face than is typical. Evidence: PCS. Frequency: 9/9. (PMID:27633801;PMID:30304524)
- Increased circulating lactate concentration (HP:0002151): Abnormally increased level of blood lactate (2-hydroxypropanoic acid). Lactate is produced from pyruvate by lactate dehydrogenase during normal metabolism. The terms lactate and lactic acid are often used interchangeably but lactate (the component measured in blood) is strictly a weak base whereas lactic acid is the corresponding acid. Lactic acidosis is often used clinically to describe elevated lactate but should be reserved for cases where there is a corresponding acidosis (pH below 7.35). Evidence: PCS. Frequency: 1/1. (PMID:29232904)
- Delayed gross motor development (HP:0002194): A type of motor delay characterized by a delay in acquiring the ability to control the large muscles of the body for walking, running, sitting, and crawling. Evidence: PCS. Frequency: 7/7. (PMID:30304524)
- Tube feeding (HP:0033454): Feeding problem necessitating food and nutrient delivery via a tube. Evidence: PCS. Frequency: 8/8. (PMID:29232904;PMID:30304524)
- Exocrine pancreatic insufficiency (HP:0001738): Impaired function of the exocrine pancreas associated with a reduced ability to digest foods because of lack of digestive enzymes. Evidence: PCS. Frequency: 7/7. (PMID:30304524)
- Autosomal recessive inheritance (HP:0000007): 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). Evidence: PCS. (PMID:27633801)
- Microvesicular hepatic steatosis (HP:0001414): A form of hepatic steatosis characterized by the presence of small, lipid-laden vesicles in the affected hepatocytes. Evidence: PCS. Frequency: 1/2. (PMID:27633801)
- Hepatic steatosis (HP:0001397): Steatosis is a term used to denote lipid accumulation within hepatocytes. Evidence: PCS. Frequency: 2/3. (PMID:27633801;PMID:29232904)
- Nyctalopia (HP:0000662): Inability to see well at night or in poor light. Evidence: PCS. Frequency: 1/1. (PMID:29232904)
- Agenesis of corpus callosum (HP:0001274): Absence of the corpus callosum as a result of the failure of the corpus callosum to develop, which can be the result of a failure in any one of the multiple steps of callosal development including cellular proliferation and migration, axonal growth or glial patterning at the midline. Evidence: PCS. Frequency: 1/1. (PMID:29232904)
- Cirrhosis (HP:0001394): A chronic disorder of the liver in which liver tissue becomes scarred and is partially replaced by regenerative nodules and fibrotic tissue resulting in loss of liver function. Evidence: PCS. Frequency: 1/2. (PMID:27633801)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: PCS. Frequency: 1/2. (PMID:27633801)
- Weakness of facial musculature (HP:0030319): Reduced strength of one or more muscles innervated by the facial nerve (the seventh cranial nerve). Evidence: PCS. Frequency: 1/2. (PMID:27633801)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 2/3. (PMID:27633801;PMID:29232904)
- 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: 1/7. (PMID:30304524)
- Anemia (HP:0001903): A reduction in erythrocytes volume or hemoglobin concentration. Evidence: PCS. Frequency: 3/7. (PMID:30304524)
- Hypoglycemia (HP:0001943): A decreased concentration of glucose in the blood. Evidence: PCS. Frequency: 5/7. (PMID:30304524)
- Lymphadenopathy (HP:0002716): Enlargement (swelling) of a lymph node. Evidence: PCS. Frequency: 1/2. (PMID:27633801)
- Multiple pulmonary cysts (HP:0005948): The presence of multiple lung cysts. Evidence: PCS. Frequency: 1/2. (PMID:27633801)
- Polysplenia (HP:0001748): Polysplenia is a congenital disease manifested by multiple small accessory spleens. Evidence: PCS. Frequency: 1/2. (PMID:27633801)
- Ventriculomegaly (HP:0002119): An increase in size of the ventricular system of the brain. Evidence: PCS. Frequency: 1/2. (PMID:27633801)
- Accessory spleen (HP:0001747): An accessory spleen is a round, iso-echogenic, homogenic and smooth structure and is seen as a normal variant mostly on the medial contour of the spleen, near the hilus or around the lower pole. This has no pathogenic relevance. Evidence: PCS. Frequency: 1/2. (PMID:27633801)
- 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: PCS. Frequency: 1/2. (PMID:27633801)
- Macronodular cirrhosis (HP:0006577): A type of cirrhosis characterized by the presence of large regenerative nodules. Evidence: PCS. Frequency: 1/2. (PMID:27633801)
- 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:29232904)
- Splenomegaly (HP:0001744): Abnormal increased size of the spleen. Evidence: PCS. Frequency: 1/2. (PMID:27633801)
- Premature birth (HP:0001622): The birth of a baby of less than 37 weeks of gestational age. Evidence: IEA. Frequency: 3/7. Onset: Congenital onset (HP:0003577). (PMID:30304524)
- Bilateral sensorineural hearing impairment (HP:0008619): A form of sensorineural hearing impairment that affects both ears. Evidence: PCS. Frequency: 7/7. (PMID:30304524)
- Wide nasal bridge (HP:0000431): Increased breadth of the nasal bridge (and with it, the nasal root). Evidence: PCS. Frequency: 1/2. (PMID:27633801)
- 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: 2/2. (PMID:27633801)
- Profound hearing impairment (HP:0012715): A profound (essentially complete) form of hearing impairment. Evidence: PCS. Frequency: 1/1. (PMID:29232904)
- Depressed nasal bridge (HP:0005280): Posterior positioning of the nasal root in relation to the overall facial profile for age. Evidence: PCS. Frequency: 1/2. (PMID:27633801)
- Infra-orbital fold (HP:0011232): Elevated ridge(s) of skin starting well below the medial aspect of the lower lid that curves gradually upward toward and/or across the nasal bridge. Evidence: PCS. Frequency: 1/2. (PMID:27633801)
- Microretrognathia (HP:0000308): A form of developmental hypoplasia of the mandible in which the mandible is mislocalised posteriorly. Evidence: PCS. Frequency: 1/2. (PMID:27633801)
- Neonatal hypoglycemia (HP:0001998). Evidence: PCS. Frequency: 1/1. (PMID:29232904)
- Growth delay (HP:0001510): A deficiency or slowing down of growth pre- and postnatally. Evidence: PCS. Frequency: 7/7. (PMID:30304524)
- Primary amenorrhea (HP:0000786). Evidence: PCS. Frequency: 1/1. (PMID:29232904)