Phenotypes associated with the disease neurofibromatosis type 1 (OMIM:162200):
- Mild intellectual disability (HP:0001256): Mild intellectual disability (ID) is defined as a type of ID characterized by mildly sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) the range of 50-69. Evidence: IEA. (OMIM:162200)
- 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: PCS. Frequency: 50/385. (PMID:11106357)
- 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: PCS. Frequency: 19/437. (PMID:29566708)
- Sphenoid wing dysplasia (HP:6001124): Hypoplasia or aplasia of the greater or lesser wing of the sphenoid bone, typically resulting in widening of the superior orbital fissure, elevation of the [lesser sphenoid wing, and ipsilateral orbital enlargement. Evidence: TAS. (OMIM:162200)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. (PMID:20301288)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. (PMID:20301288)
- Lipoma (HP:0012032): Benign neoplasia derived from lipoblasts or lipocytes of white or brown fat. May be angiomatous or hibernomatous. Evidence: PCS. Frequency: 9/328. (PMID:7607663;PMID:26178382;PMID:36659944;PMID:9101303;PMID:8664912;PMID:29290338;PMID:17160901)
- 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: 3/15. (PMID:38596211)
- Meningioma (HP:0002858): The presence of a meningioma, i.e., a benign tumor originating from the dura mater or arachnoid mater. Evidence: IEA. (OMIM:162200)
- 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: PCS. Frequency: 186/300. (PMID:10204844)
- 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: PCS. Frequency: 435/546. (PMID:7607663;PMID:26178382;PMID:36659944;PMID:38596211;PMID:9101303;PMID:8664912;PMID:10204844;PMID:29290338)
- 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: IEA. (OMIM:162200)
- Rhabdomyosarcoma (HP:0002859). Evidence: IEA. (OMIM:162200)
- Multiple cafe-au-lait spots (HP:0007565): The presence of six or more cafe-au-lait spots. Evidence: PCS. Frequency: 677/781. (PMID:7607663;PMID:20513137;PMID:26178382;PMID:36659944;PMID:38596211;PMID:9101303;PMID:8664912;PMID:10204844;PMID:29290338)
- Genu valgum (HP:0002857): The legs angle inward, such that the knees are close together and the ankles far apart. Evidence: IEA. (OMIM:162200)
- Spina bifida (HP:0002414): Incomplete closure of the embryonic neural tube, whereby some vertebral arches remain unfused and open. The mildest form is spina bifida occulta, followed by meningocele and meningomyelocele. Evidence: IEA. Frequency: 151/357. (OMIM:162200)
- 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: PCS. Frequency: 18/267. (PMID:26178382;PMID:29290338;PMID:17160901)
- Renal artery stenosis (HP:0001920): The presence of stenosis of the renal artery. Evidence: PCS. Frequency: 4/641. (PMID:10204844;PMID:29290338)
- Parathyroid adenoma (HP:0002897): A benign tumor of the parathyroid gland that can cause hyperparathyroidism. Evidence: IEA. (OMIM:162200)
- Neurofibroma (HP:0001067): A benign peripheral nerve sheath tumor that generally appears as a soft, skin-colored papule or small subcutaneous nodule. Individuals with neurofibromatosis can have numerous neurofibromas. Evidence: PCS. Frequency: 297/457. (PMID:7607663;PMID:20513137;PMID:26178382;PMID:38596211;PMID:9101303;PMID:8664912;PMID:10204844;PMID:29290338)
- Downslanted palpebral fissures (HP:0000494): The palpebral fissure inclination is more than two standard deviations below the mean. Evidence: PCS. Frequency: 4/15. (PMID:38596211)
- Few cafe-au-lait spots (HP:0007429): The presence of two to five cafe-au-lait macules. Evidence: PCS. Frequency: 48/56. (PMID:20513137;PMID:26178382;PMID:38596211;PMID:29290338)
- Breast carcinoma (HP:0003002): The presence of a carcinoma of the breast. Evidence: PCS. Frequency: 1/148. (PMID:7607663;PMID:36659944;PMID:9101303;PMID:8664912;PMID:29290338)
- Colon cancer (HP:0003003). Evidence: PCS. Frequency: 1/148. (PMID:7607663;PMID:36659944;PMID:9101303;PMID:8664912;PMID:29290338)
- Cerebellar glioma (HP:0010795): A glioma affecting the cerebellum. Evidence: PCS. Frequency: 2/163. (PMID:7607663;PMID:38596211;PMID:36659944;PMID:9101303;PMID:8664912;PMID:29290338)
- 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: PCS. (OMIM:162200)
- 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: 24/439. (PMID:7607663;PMID:26178382;PMID:36659944;PMID:38596211;PMID:9101303;PMID:8664912;PMID:29618358;PMID:29290338;PMID:17160901)
- Glioma (HP:0009733): The presence of a glioma, which is a neoplasm of the central nervous system originating from a glial cell (astrocytes or oligodendrocytes). Evidence: PCS. Frequency: 2/2. (PMID:26178382;PMID:38596211)
- 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: 13/274. (PMID:26178382;PMID:38596211;PMID:29290338)
- Plexiform neurofibroma (HP:0009732): A neurofibroma in which Schwann cells proliferate inside the nerve sheath, producing an irregularly thickened, distorted, tortuous structure. Evidence: PCS. Frequency: 139/554. (PMID:7607663;PMID:20513137;PMID:23035791;PMID:26178382;PMID:36659944;PMID:38596211;PMID:9101303;PMID:8664912;PMID:29290338;PMID:17160901)
- Medullary thyroid carcinoma (HP:0002865): The presence of a medullary carcinoma of the thyroid gland. Evidence: PCS. Frequency: 1/148. (PMID:7607663;PMID:36659944;PMID:9101303;PMID:8664912;PMID:29290338)
- Spinal neurofibroma (HP:0009735): A neurofibroma (benign peripheral nerve sheath tumor) localized in the spine. Evidence: PCS. Frequency: 34/354. (PMID:10204844;PMID:29290338)
- Embryonal rhabdomyosarcoma (HP:0006743). Evidence: PCS. Frequency: 3/148. (PMID:7607663;PMID:36659944;PMID:9101303;PMID:8664912;PMID:29290338)
- Optic nerve glioma (HP:0009734): A glioma originating in the optic nerve or optic chiasm. Evidence: PCS. Frequency: 64/476. (PMID:20513137;PMID:26178382;PMID:38596211;PMID:8664912;PMID:10204844;PMID:29290338)
- 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:10204844)
- Lisch nodules (HP:0009737): The presence of pigmented, oval and dome-shaped raised hamartomatous nevi of the iris.. Evidence: PCS. Frequency: 240/533. (PMID:7607663;PMID:20513137;PMID:26178382;PMID:38596211;PMID:36659944;PMID:8664912;PMID:10204844;PMID:29290338;PMID:17160901)
- 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: 2/15. (PMID:38596211)
- Pheochromocytoma (HP:0002666): Pheochromocytomas (also known as chromaffin tumors) produce, store, and secrete catecholamines. Pheochromocytomas usually originate from the adrenal medulla but may also develop from chromaffin cells in or about sympathetic ganglia. A common symptom of pheochromocytoma is hypertension owing to release of catecholamines. Evidence: PCS. Frequency: 3/3. (PMID:25130111)
- Tibial pseudarthrosis (HP:0009736): Pseudarthrosis, or "false joint" of the tibia is the result of a developmental failure in the tibia progressing to spontaneous fracture and subsequent fibrous nonunion. The fracture is rarely present at birth but commonly develops during the first 18 months of life. Evidence: PCS. Frequency: 10/300. (PMID:10204844)
- Hypsarrhythmia (HP:0002521): Hypsarrhythmia is abnormal interictal high amplitude waves and a background of irregular spikes. There is continuous (during wakefulness), high-amplitude (>200 Hz), generalized polymorphic slowing with no organized background and multifocal spikes demonstrated by electroencephalography (EEG). Evidence: PCS. (PMID:18802710)
- Hypopigmented macule (HP:0020073): A white or lighter patch of skin that may appear anywhere on the body and are caused by decreased skin pigmentation. Evidence: PCS. (PMID:17105749)
- 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: 2/223. (PMID:26178382;PMID:29290338)
- Overgrowth (HP:0001548): Excessive postnatal growth which may comprise increased weight, increased length, and/or increased head circumference. Evidence: IEA. (OMIM:162200)
- Pericarditis (HP:0001701): Inflammation of the sac-like covering around the heart (pericardium). Evidence: PCS. Frequency: 1/118. (PMID:29290338)
- 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: PCS. Frequency: 48/128. (PMID:31326214)
- Aqueductal stenosis (HP:0002410): Stenosis of the cerebral aqueduct (also known as the mesencephalic duct, aqueductus mesencephali, or aqueduct of Sylvius), which connects the third cerebral ventricle in the diencephalon to the fourth ventricle, which is between the pons and cerebellum. Evidence: IEA. (OMIM:162200)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 56/365. (PMID:7607663;PMID:20513137;PMID:26178382;PMID:36659944;PMID:38596211;PMID:9101303;PMID:8664912;PMID:29290338;PMID:17160901)
- Freckling (HP:0001480): The presence 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: PCS. Frequency: 146/224. (PMID:20513137;PMID:26178382;PMID:29290338;PMID:17160901)
- Coarctation of aorta (HP:0001680): Coarctation of the aorta is a narrowing or constriction of a segment of the aorta. Evidence: PCS. Frequency: 1/118. (PMID:29290338)
- Pilocytic astrocytoma (HP:0033680): The most common form of astrocytoma (WHO Grade I) in childhood. These typically have MAPK signaling pathway abnormalities. Evidence: PCS. Frequency: 1/148. (PMID:7607663;PMID:36659944;PMID:9101303;PMID:8664912;PMID:29290338)
- Astrocytoma (HP:0009592): Astrocytoma is a neoplasm of the central nervous system derived from astrocytes. Astrocytes are a type of glial cell, and thus astrocytoma is a subtype of glioma. Evidence: PCS. Frequency: 2/137. (PMID:26178382;PMID:29290338)
- 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: PCS. Frequency: 1/118. (PMID:29290338)
- Kyphosis (HP:0002808): Exaggerated anterior convexity of the thoracic vertebral column. Evidence: PCS. Frequency: 2/145. (PMID:7607663;PMID:26178382;PMID:38596211;PMID:36659944;PMID:9101303;PMID:8664912)
- Mitral stenosis (HP:0001718): An abnormal narrowing of the orifice of the mitral valve. Evidence: PCS. Frequency: 1/118. (PMID:29290338)
- Hypertension (HP:0000822): The presence of chronic increased pressure in the systemic arterial system. Evidence: PCS. Frequency: 10/238. (OMIM:162200;PMID:26178382;PMID:29290338)
- 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: PCS. Frequency: 151/357. Onset: Childhood onset (HP:0011463). (PMID:10204844)
- 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: PCS. Frequency: 11/15. (PMID:38596211)
- 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: PCS. Frequency: 1/1. (PMID:9101303)
- 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: PCS. Frequency: 8/22. (PMID:26178382)
- 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: PCS. Frequency: 1/1. (PMID:36659944)
- 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: PCS. Frequency: 2/2. (PMID:8664912)
- 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: PCS. Frequency: 69/130. (PMID:29290338)
- 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: PCS. Frequency: 3/267. (PMID:26178382;PMID:29290338;PMID:17160901)
- Webbed neck (HP:0000465): Pterygium colli is a congenital skin fold that runs along the sides of the neck down to the shoulders. It involves an ectopic fibrotic facial band superficial to the trapezius muscle. Excess hair-bearing skin is also present and extends down the cervical region well beyond the normal hairline. Evidence: PCS. Frequency: 1/15. (PMID:38596211)
- Glaucoma (HP:0000501): Glaucoma refers loss of retinal ganglion cells in a characteristic pattern of optic neuropathy usually associated with increased intraocular pressure. Evidence: PCS. (PMID:22138687)