- Multiple cafe-au-lait spots (HP:0007565): The presence of six or more cafe-au-lait spots. Evidence: TAS. Frequency: Very frequent (HP:0040281). (ORPHA:137605)
- Atypical behavior (HP:0000708): Atypical behavior is an abnormality in a person's actions that can be controlled or modulated by the will of the individual. While abnormal behaviors can be difficult to control, they are distinct from other abnormal actions that cannot be affected by the individual's will. Evidence: TAS. Frequency: Frequent (HP:0040282). (ORPHA:137605)
- 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:137605)
- 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:137605)
- 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:137605)
- 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: Occasional (HP:0040283). (ORPHA:137605)
- Short attention span (HP:0000736): Reduced attention span characterized by distractibility and impulsivity. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:137605)
- Hyperactivity (HP:0000752): Hyperactivity is a condition characterized by constant and unusually high levels of activity, even in situations where it is deemed inappropriate. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:137605)
- Abnormal sternum morphology (HP:0000766): An anomaly of the sternum, also known as the breastbone. Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:137605)
- Multiple lipomas (HP:0001012): The presence of multiple lipomas (a type of benign tissue made of fatty tissue). Evidence: TAS. Frequency: Occasional (HP:0040283). (ORPHA:137605)
- 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:137605)
- Hearing impairment (HP:0000365): A decreased magnitude of the sensory perception of sound. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137605)
- 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: Very rare (HP:0040284). (ORPHA:137605)
- 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: Very rare (HP:0040284). (ORPHA:137605)
- Kidney stone (HP:0000787): Kidney stones (calculi) are mineral concretions in the renal calyces and pelvis that are found free or attached to the renal papillae. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137605)
- Xanthelasma (HP:0001114): The presence of xanthomata in the skin of the eyelid. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137605)
- 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: Very rare (HP:0040284). (ORPHA:137605)
- 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: Very rare (HP:0040284). (ORPHA:137605)
- Motor delay (HP:0001270): A type of Developmental delay characterized by a delay in acquiring motor skills. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137605)
- Dystonia (HP:0001332): An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137605)
- 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:137605)
- 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:137605)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137605)
- Nephroblastoma (HP:0002667): The presence of a nephroblastoma, which is a neoplasm of the kidney that primarily affects children. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137605)
- Clinodactyly of the 5th finger (HP:0004209): Clinodactyly refers to a bending or curvature of the fifth finger in the radial direction (i.e., towards the 4th finger). Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137605)
- Acute monocytic leukemia (HP:0004845): The accumulation of transformed primitive hematopoietic blast cells, which lose their ability of normal differentiation and proliferation. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137605)
- Paroxysmal atrial tachycardia (HP:0006671). Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137605)
- 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: Very rare (HP:0040284). (ORPHA:137605)
- Chiari type I malformation (HP:0007099): Arnold-Chiari type I malformation refers to a relatively mild degree of herniation of the posteroinferior region of the cerebellum (the cerebellar tonsils) into the cervical canal with little or no displacement of the fourth ventricle. It is characterized by one or both pointed (not rounded) cerebellar tonsils that project 5 mm below the foramen magnum, measured by a line drawn from the basion to the opisthion (McRae Line). Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137605)
- Vestibular schwannoma (HP:0009588): A vestibular schwannoma (also known as acoustic neuroma, acoustic neurinoma, or acoustic neurilemoma) is a benign, usually slow-growing tumor that develops from the VIIIth cranial nerve supplying the inner ear. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137605)
- Polydactyly (HP:0010442): A congenital anomaly characterized by the presence of supernumerary fingers or toes. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137605)
- Non-small cell lung carcinoma (HP:0030358). Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137605)
- Male urethral meatus stenosis (HP:0032077): An abnormal narrowing of the urethral opening (meatus) of the penis. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137605)
- Gastrointestinal desmoid tumor (HP:0100245): Benign, slow-growing tumors without any metastatic potential. Despite their benign nature, they can damage nearby structures causing organ dysfunction. Histologically they resemble low-grade fibrosarcomas, but they are very locally aggressive and tend to recur even after complete resection. There is a tendency for recurrence in the setting of prior surgery and the most common localisation of these tumors is intraabdominal from smooth muscle cells of the instestine. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137605)
- Cognitive impairment (HP:0100543): Abnormal cognition is characterized by deficits in thinking, reasoning, or remembering. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137605)
- Ovarian neoplasm (HP:0100615): A tumor (abnormal growth of tissue) of the ovary. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137605)
- Brain imaging abnormality (HP:0410263): An anomaly of metabolism or structure of the brain identified by imaging. Evidence: TAS. Frequency: Very rare (HP:0040284). (ORPHA:137605)
These phenotypes are associated with the disease Legius syndrome (ORPHA:137605).
The following phenotypes are NOT associated with this disease:
- 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: TAS. (ORPHA:137605)
- Optic nerve glioma (HP:0009734): A glioma originating in the optic nerve or optic chiasm. Evidence: TAS. (ORPHA:137605)
- Lisch nodules (HP:0009737): The presence of pigmented, oval and dome-shaped raised hamartomatous nevi of the iris.. Evidence: TAS. (ORPHA:137605)
- Neoplasm of the central nervous system (HP:0100006): A neoplasm of the central nervous system. Evidence: TAS. (ORPHA:137605)
- Diaphyseal dysplasia (HP:0100252). Evidence: TAS. (ORPHA:137605)