Phenotypes associated with the disease Neurofibromatosis type 1 due to NF1 mutation or intragenic deletion (ORPHA:363700):
- 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: Very frequent (HP:0040281). (ORPHA:363700)
- Cafe-au-lait spot (HP:0000957): Cafe-au-lait spots are hyperpigmented lesions that can vary in color from light brown to dark brown with smooth borders and having a size of 1.5 cm or more in adults and 0.5 cm or more in children. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:363700)
- Macrocephaly (HP:0000256): Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:363700)
- Coarse facial features (HP:0000280): Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:363700)
- Broad neck (HP:0000475): Increased side-to-side width of the neck. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:363700)
- Abnormality of the skeletal system (HP:0000924): An abnormality of the skeletal system. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:363700)
- Axillary freckling (HP:0000997): The presence in the axillary region (armpit) of an increased number of freckles, small circular spots on the skin that are darker than the surrounding skin because of deposits of melanin. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:363700)
- Large hands (HP:0001176). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:363700)
- 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: TAS. Frequency: Frequent (HP:0040282). (ORPHA:363700)
- Specific learning disability (HP:0001328): Impairment of certain skills such as reading or writing, coordination, self-control, or attention that interfere with the ability to learn. The impairment is not related to a global deficiency of intelligence. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:363700)
- 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:363700)
- Abnormal heart morphology (HP:0001627): Any structural anomaly of the heart. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:363700)
- Long foot (HP:0001833): Increased back to front length of the foot. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:363700)
- Abnormal facial shape (HP:0001999): An abnormal morphology (form) of the face or its components. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:363700)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:363700)
- Attention deficit hyperactivity disorder (HP:0007018): Attention deficit hyperactivity disorder (ADHD) manifests at age 2-3 years or by first grade at the latest. The main symptoms are distractibility, impulsivity, hyperactivity, and often trouble organizing tasks and projects, difficulty going to sleep, and social problems from being aggressive, loud, or impatient. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:363700)
- Speech articulation difficulties (HP:0009088): Impairment in the physical production of speech sounds. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:363700)
- Lisch nodules (HP:0009737): The presence of pigmented, oval and dome-shaped raised hamartomatous nevi of the iris.. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:363700)
- Proportionate tall stature (HP:0011407). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:363700)
- Bone cyst (HP:0012062): A fluid filled cavity that develops with a bone. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:363700)
- Neurodevelopmental delay (HP:0012758): Neurodevelopmental delay (NDD) refers to delays in the maturation of the brain and central nervous system; infants and young children with NDD may experience delays in the development of one or more skills including gross motor abilities, fine-motor coordination, language abilities and ability to solve increasingly complex problems. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:363700)
- Inguinal freckling (HP:0030052): The presence in the inguinal region (groin) of an increased number of freckles, small circular spots on the skin that are darker than the surrounding skin because of deposits of melanin. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:363700)
- Subcutaneous neurofibroma (HP:0100698): A neurofibroma (benign peripheral nerve sheath tumor) localized in the subcutis (subcutaneous region). Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:363700)
- Brain imaging abnormality (HP:0410263): An anomaly of metabolism or structure of the brain identified by imaging. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:363700)
- 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: Occasional (HP:0040283). (ORPHA:363700)
- 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: Occasional (HP:0040283). (ORPHA:363700)
- 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: Occasional (HP:0040283). (ORPHA:363700)
- Facial asymmetry (HP:0000324): An abnormal difference between the left and right sides of the face. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:363700)
- Narrow forehead (HP:0000341): Width of the forehead or distance between the frontotemporales is more than two standard deviations below the mean (objective); or apparently narrow intertemporal region (subjective). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:363700)
- 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: Occasional (HP:0040283). (ORPHA:363700)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:363700)
- Protruding ear (HP:0000411): Angle formed by the plane of the ear and the mastoid bone greater than the 97th centile for age (objective); or, outer edge of the helix more than 2 cm from the mastoid at the point of maximum distance (objective). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:363700)
- Hypotelorism (HP:0000601): Interpupillary distance less than 2 SD below the mean (alternatively, the appearance of an decreased interpupillary distance or closely spaced eyes). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:363700)
- 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: TAS. Frequency: Occasional (HP:0040283). (ORPHA:363700)
- 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:363700)
- 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: Occasional (HP:0040283). (ORPHA:363700)
- 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: Occasional (HP:0040283). (ORPHA:363700)
- Pes cavus (HP:0001761): An increase in height of the medial longitudinal arch of the foot that does not flatten on weight bearing (i.e., a distinctly hollow form of the sole of the foot when it is bearing weight). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:363700)
- Prominent glabella (HP:0002057): Forward protrusion of the glabella. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:363700)
- Hypoplasia of the corpus callosum (HP:0002079): Underdevelopment of the corpus callosum. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:363700)
- Genu valgum (HP:0002857): The legs angle inward, such that the knees are close together and the ankles far apart. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:363700)
- Short stature (HP:0004322): A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:363700)
- Abnormal dental pulp morphology (HP:0006479): An abnormality of the dental pulp. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:363700)
- Optic nerve glioma (HP:0009734): A glioma originating in the optic nerve or optic chiasm. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:363700)
- Spinal neurofibroma (HP:0009735): A neurofibroma (benign peripheral nerve sheath tumor) localized in the spine. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:363700)
- Impaired visuospatial constructive cognition (HP:0010794): Reduced ability affecting mainly visuospatial cognition which may be tested using pattern construction (for example by Differential Ability Scales, which test a person's strengths and weaknesses across a range of intellectual abilities). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:363700)
- Abnormal renal morphology (HP:0012210): Any structural anomaly of the kidney. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:363700)
- Thick vermilion border (HP:0012471): Increased width of the skin of vermilion border region of upper lip. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:363700)
- Malignant peripheral nerve sheath tumor (HP:0100697): Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas (STS) with nerve sheath differentiation and a tendency to metastasize. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:363700)
- Abnormality of the sphenoid sinus (HP:0430022): An abnormality of the sphenoid sinus, one of the mucosa-lined, normally air-filled paranasal sinuses of the bones of the skull. The sphenoid sinus is located within the sphenoid bone. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:363700)
- Hydronephrosis (HP:0000126): Severe distention of the kidney with dilation of the renal pelvis and calices. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:363700)
- Hydrocephalus (HP:0000238): Hydrocephalus is an active distension of the ventricular system of the brain resulting from inadequate passage of CSF from its point of production within the cerebral ventricles to its point of absorption into the systemic circulation. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:363700)
- Sinusitis (HP:0000246): Inflammation of the paranasal sinuses owing to a viral, bacterial, or fungal infection, allergy, or an autoimmune reaction. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:363700)
- Hemangioma (HP:0001028): A hemangioma is a benign tumor characterized by blood-filled spaces lined by benign endothelial cells. A hemangioma characterized by large endothelial spaces (caverns) is called a cavernous hemangioma (in contrast to a hemangioma with small endothelial spaces, which is called capillary hemangioma). Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:363700)
- 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: TAS. Frequency: Very rare (HP:0040284). (ORPHA:363700)
- Atrial septal defect (HP:0001631): Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:363700)
- Mitral valve prolapse (HP:0001634): One or both of the leaflets (cusps) of the mitral valve bulges back into the left atrium upon contraction of the left ventricle. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:363700)
- 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:363700)
- Pulmonic stenosis (HP:0001642): A narrowing of the right ventricular outflow tract that can occur at the pulmonary valve (valvular stenosis), below the pulmonary valve (infundibular stenosis), or above the pulmonary valve (supravalvar stenosis). Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:363700)
- Mitral regurgitation (HP:0001653): An abnormality of the mitral valve characterized by insufficiency or incompetence of the mitral valve resulting in retrograde leaking of blood through the mitral valve upon ventricular contraction. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:363700)
- Patent foramen ovale (HP:0001655): Failure of the foramen ovale to seal postnatally, leaving a potential conduit between the left and right cardiac atria. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:363700)
- Headache (HP:0002315): Cephalgia, or pain sensed in various parts of the head, not confined to the area of distribution of any nerve. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:363700)
- Kyphoscoliosis (HP:0002751): An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:363700)
- Abnormal tibia morphology (HP:0002992): Abnormality of the tibia (shinbone). Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:363700)
- Hyperlordosis (HP:0003307): Abnormally increased curvature (anterior concavity) of the lumbar or cervical spine. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:363700)
- Renal hypoplasia/aplasia (HP:0008678): Absence or underdevelopment of the kidney. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:363700)
- Macule (HP:0012733): A flat, distinct, discolored area of skin less than 1 cm wide that does not involve any change in the thickness or texture of the skin. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:363700)
- Lower limb dysmetria (HP:0020035): A lack of coordination of leg movement manifested by undershoot or overshoot of the intended position of the leg. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:363700)
- Ossifying fibroma (HP:0030426): A benign central bone tumor composed of fibrous connective tissue within which bone is formed. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:363700)
- Granuloma (HP:0032252): A compact, organized collection of mature mononuclear phagocytes, which may be but is not necessarily accompanied by accessory features such as necrosis. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:363700)
- Schwannoma (HP:0100008): A benign nerve sheath tumor composed of Schwann cells. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:363700)