Phenotypes associated with the disease Noonan syndrome 1 (OMIM:163950):
- Abnormal bleeding (HP:0001892): An abnormal susceptibility to bleeding, often referred to as a bleeding diathesis. A bleeding diathesis may be related to vascular, platelet and coagulation defects. Evidence: PCS. Frequency: 3/18. (PMID:15240615)
- 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: 15/28. (PMID:12634870)
- Reduced factor XII activity (HP:0004841): Decreased activity of coagulation factor XII. Factor XII (fXII) is part of the intrinsic coagulation pathway and binds to exposed collagen at site of vessel wall injury, activated by high-MW kininogen and kallikrein, thereby initiating the coagulation cascade. Evidence: IEA. (OMIM:163950)
- Woolly hair (HP:0002224): The term wooly hair refers to an abnormal variant of hair that is fine, with tightly coiled curls, and often hypopigmented. Optical microscopy may reveal the presence of tight spirals and a clear diameter reduction as compared with normal hair. Electron microscopy may show flat, oval hair shafts with reduced transversal diameter. Evidence: PCS. Frequency: 9/107. (PMID:32164556)
- Failure to thrive in infancy (HP:0001531). Evidence: IEA. (OMIM:163950)
- Hearing impairment (HP:0000365): A decreased magnitude of the sensory perception of sound. Evidence: PCS. Frequency: 2/17. (PMID:15240615)
- 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: 41/56. Onset: Infantile onset (HP:0003593). (PMID:15723289)
- 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: 43/107. (PMID:32164556)
- Superior pectus carinatum (HP:0000917): Pectus carinatum affecting primarily the superior part of the sternum. Evidence: IEA. (OMIM:163950)
- Dry skin (HP:0000958): Skin characterized by the lack of natural or normal moisture. Evidence: PCS. Frequency: 5/107. (PMID:32164556)
- Shield chest (HP:0000914): A broad chest. Evidence: IEA. (OMIM:163950)
- Synovitis (HP:0100769). Evidence: TAS. (OMIM:163950)
- 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: PCS. Frequency: 10/107. (PMID:32164556)
- Pectus excavatum of inferior sternum (HP:0000915): Pectus excavatum (defect of the chest wall characterized by depression of the sternum) affecting primarily the inferior region of the sternum. Evidence: IEA. (OMIM:163950)
- 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: 68/135. (PMID:12634870;PMID:32164556)
- Radial deviation of finger (HP:0009466): Bending or curvature of a finger toward the radial side (i.e., towards the thumb). The deviation is at the metacarpal-phalangeal joint, and this finding is distinct from clinodactyly. Evidence: PCS. (OMIM:163950)
- Postnatal growth retardation (HP:0008897): Slow or limited growth after birth. Evidence: PCS. (OMIM:163950)
- Patent ductus arteriosus (HP:0001643): In utero, the ductus arteriosus (DA) serves to divert ventricular output away from the lungs and toward the placenta by connecting the main pulmonary artery to the descending aorta. A patent ductus arteriosus (PDA) in the first 3 days of life is a physiologic shunt in healthy term and preterm newborn infants, and normally is substantially closed within about 24 hours after bith and completely closed after about three weeks. Failure of physiologcal closure is referred to a persistent or patent ductus arteriosus (PDA). Depending on the degree of left-to-right shunting, PDA can have clinical consequences. Evidence: IEA. (OMIM:163950)
- Cystic hygroma (HP:0000476): A cystic lymphatic lesion of the neck. Evidence: IEA. (OMIM:163950)
- Lymphedema (HP:0001004): Localized fluid retention and tissue swelling caused by a compromised lymphatic system. Evidence: IEA. (OMIM:163950)
- 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: 92/181. (PMID:15723289;PMID:32164556;PMID:15240615)
- 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: PCS. Frequency: 4/17. (PMID:15240615)
- Kyphoscoliosis (HP:0002751): An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane. Evidence: TAS. (OMIM:163950)
- Cleft palate (HP:0000175): Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate). Evidence: PCS. Frequency: 1/18. (PMID:15240615)
- Downslanted palpebral fissures (HP:0000494): The palpebral fissure inclination is more than two standard deviations below the mean. Evidence: PCS. Frequency: 19/28. (PMID:12634870)
- Chylothorax (HP:0010310): Accumulation of excessive amounts of lymphatic fluid (chyle) in the pleural cavity. Evidence: PCS. Frequency: 1/18. (PMID:15240615)
- 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. (OMIM:163950)
- Sensorineural hearing impairment (HP:0000407): A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve. Evidence: PCS. (OMIM:163950)
- Abnormal sternum morphology (HP:0000766): An anomaly of the sternum, also known as the breastbone. Evidence: PCS. Frequency: 3/18. (PMID:15240615)
- Dental malocclusion (HP:0000689): Dental malocclusion refers to an abnormality of the occlusion, or alignment, of the teeth and the way the upper and lower teeth fit together, resulting in overcrowding of teeth or in abnormal bite patterns. Evidence: IEA. (OMIM:163950)
- High, narrow palate (HP:0002705): The presence of a high and narrow palate. Evidence: TAS. (OMIM:163950)
- Hypospadias (HP:0000047): Abnormal position of urethral meatus on the ventral penile shaft (underside) characterized by displacement of the urethral meatus from the tip of the glans penis to the ventral surface of the penis, scrotum, or perineum. Evidence: PCS. Frequency: 1/8. (PMID:15240615)
- 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:11704759)
- 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: 96/137. (PMID:12634870;PMID:32164556)
- Triangular face (HP:0000325): Facial contour, as viewed from the front, triangular in shape, with breadth at the temples and tapering to a narrow chin. Evidence: PCS. (OMIM:163950)
- Brachydactyly (HP:0001156): Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here. Evidence: IEA. (OMIM:163950)
- Low posterior hairline (HP:0002162): Hair on the neck extends more inferiorly than usual. Evidence: PCS. Frequency: 86/138. (PMID:12634870;PMID:32164556)
- Male infertility (HP:0003251). Evidence: TAS. (OMIM:163950)
- Juvenile myelomonocytic leukemia (HP:0012209): Juvenile myelomonocytic leukemia (JMML) is a lethal myeloproliferative disease of young childhood characterized clinically by overproduction of myelomonocytic cells and by the in vitro phenotype of hematopoietic progenitor hypersensitivity to granulocyte-macrophage colony-stimulating factor. Evidence: PCS. Frequency: 2/18. (PMID:15240615)
- 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: 5/107. Onset: Congenital onset (HP:0003577). (PMID:32164556)
- Broad forehead (HP:0000337): Width of the forehead or distance between the frontotemporales is more than two standard deviations above the mean (objective); or apparently increased distance between the two sides of the forehead. Evidence: PCS. Frequency: 34/107. (PMID:32164556)
- Feeding difficulties in infancy (HP:0008872): Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention. Evidence: PCS. Frequency: 35/56. Onset: Infantile onset (HP:0003593). (PMID:15723289)
- Amegakaryocytic thrombocytopenia (HP:0004859): Thrombocytopenia related to lack of or severe reduction in the count of megakaryocytes. Evidence: IEA. (OMIM:163950)
- Bruising susceptibility (HP:0000978): An ecchymosis (bruise) refers to the skin discoloration caused by the escape of blood into the tissues from ruptured blood vessels. This term refers to an abnormally increased susceptibility to bruising. The corresponding phenotypic abnormality is generally elicited on medical history as a report of frequent ecchymoses or bruising without adequate trauma. Evidence: PCS. Frequency: 32/56. (PMID:15723289)
- Clinodactyly (HP:0030084): An angulation of a digit at an interphalangeal joint in the plane of the palm (finger) or sole (toe). Evidence: TAS. (OMIM:163950)
- 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: IEA. (OMIM:163950)
- Reduced factor XIII activity (HP:0008357): Decreased activity of coagulation factor XIII (also known as fibrin stabilizing factor). Activated Factor XIII cross-links fibrin polymers solidifying the clot. Evidence: TAS. (OMIM:163950)
- Wide intermamillary distance (HP:0006610): A larger than usual distance between the left and right nipple. Evidence: PCS. Frequency: 37/107. (PMID:32164556)
- Hypogonadism (HP:0000135): A decreased functionality of the gonad. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:163950)
- Coarctation of aorta (HP:0001680): Coarctation of the aorta is a narrowing or constriction of a segment of the aorta. Evidence: TAS. (OMIM:163950)
- Short neck (HP:0000470): Diminished length of the neck. Evidence: PCS. Frequency: 15/29. (PMID:12634870)
- 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: 13/181. (PMID:15723289;PMID:32164556;PMID:15240615)
- Ptosis (HP:0000508): The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective). Evidence: PCS. Frequency: 77/136. (PMID:12634870;PMID:32164556)
- Cubitus valgus (HP:0002967): Abnormal positioning in which the elbows are turned out. Evidence: PCS. Frequency: 13/107. (PMID:32164556)
- 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: 70/181. Onset: Congenital onset (HP:0003577). (PMID:15723289;PMID:32164556;PMID:15240615)
- 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: 13/32. (PMID:12634870)
- 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: 10/56. Onset: Congenital onset (HP:0003577). (PMID:12634870)
- 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: 65/107. (PMID:32164556)
- Cryptorchidism (HP:0000028): Testis in inguinal canal. That is, absence of one or both testes from the scrotum owing to failure of the testis or testes to descend through the inguinal canal to the scrotum. Evidence: PCS. Frequency: 5/8. (PMID:15240615)
- Cryptorchidism (HP:0000028): Testis in inguinal canal. That is, absence of one or both testes from the scrotum owing to failure of the testis or testes to descend through the inguinal canal to the scrotum. Evidence: PCS. Frequency: 27/32. (PMID:15723289)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: PCS. (OMIM:163950)
- Myopia (HP:0000545): An abnormality of refraction characterized by the ability to see objects nearby clearly, while objects in the distance appear blurry. Evidence: IEA. (OMIM:163950)