Phenotypes associated with the disease Noonan syndrome 13 (OMIM:619087):
- 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: 1/7. (PMID:32721402)
- Cavum septum pellucidum (HP:0002389): If the two laminae of the septum pellucidum are not fused then a fluid-filled space or cavum is present. The cavum septum pellucidum is present at birth but usually obliterates by the age of 3 to 6 months. It is up to 1cm in width and the walls are parallel. It is an enclosed space and is not part of the ventricular system or connected with the subarachnoid space. Evidence: PCS. Frequency: 1/7. (PMID:32721402)
- Limited elbow extension (HP:0001377): Limited ability to straighten the arm at the elbow joint. Evidence: PCS. Frequency: 1/7. (PMID:32721402)
- Gastroesophageal reflux (HP:0002020): A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter. Evidence: PCS. Frequency: 1/7. (PMID:32721402)
- U-Shaped upper lip vermilion (HP:0010806): Gentle upward curve of the upper lip vermilion such that the center is placed well superior to the commissures. Evidence: PCS. Frequency: 1/7. (PMID:32721402)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: PCS. Frequency: 4/7. (PMID:32721402)
- 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: PCS. Frequency: 1/7. (PMID:32721402)
- Duplicated collecting system (HP:0000081): A duplication of the collecting system of the kidney, defined as a kidney with two (instead of, normally, one) pyelocaliceal systems. The pyelocaliceal system is comprised of the renal pelvis and calices. The duplicated renal collecting system can be associated with a single ureter or with double ureters. In the latter case, the two ureters empty separately into the bladder or fuse to form a single ureteral orifice. Evidence: PCS. Frequency: 1/7. (PMID:32721402)
- Infantile spasms (HP:0012469): Infantile spasms represent a subset of "epileptic spasms". Infantile Spasms are epileptic spasms starting in the first year of life (infancy). Evidence: PCS. Frequency: 1/7. Onset: Infantile onset (HP:0003593). (PMID:32721402)
- Dry skin (HP:0000958): Skin characterized by the lack of natural or normal moisture. Evidence: PCS. Frequency: 2/7. (PMID:32721402)
- 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: 1/7. (PMID:32721402)
- Aggressive behavior (HP:0000718): Behavior or an act aimed at harming a person, animal, or physical property (e.g., acts of physical violence; shouting, swearing, and using harsh language; slashing someone's tires). Evidence: PCS. Frequency: 2/7. (PMID:32721402)
- Hoarse voice (HP:0001609): Hoarseness refers to a change in the pitch or quality of the voice, with the voice sounding weak, very breathy, scratchy, or husky. Evidence: PCS. Frequency: 1/7. (PMID:32721402)
- Blue irides (HP:0000635): A markedly blue coloration of the iris. Evidence: PCS. Frequency: 1/7. (PMID:32721402)
- 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: 5/7. (PMID:32721402)
- Hypertrichosis (HP:0000998): Hypertrichosis is increased hair growth that is abnormal in quantity or location. Evidence: PCS. Frequency: 2/7. (PMID:32721402)
- Overlapping toe (HP:0001845): Describes a foot digit resting on the dorsal surface of an adjacent digit when the foot is at rest. Initially clawing may be dynamic and only noticeable on walking. Over time the plantar plate tears, subluxation occurs at the metatarsophalangeal joint (MTPJ), and the deformity becomes permanent. Evidence: PCS. Frequency: 1/7. (PMID:32721402)
- Lymphedema (HP:0001004): Localized fluid retention and tissue swelling caused by a compromised lymphatic system. Evidence: PCS. Frequency: 1/7. (PMID:32721402)
- Metatarsus adductus (HP:0001840): The metatarsals are deviated medially (tibially), that is, the bones in the front half of the foot bend or turn in toward the body. Evidence: PCS. Frequency: 1/7. (PMID:32721402)
- Pes planus (HP:0001763): A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced. Evidence: PCS. Frequency: 3/7. (PMID:32721402)
- 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: 6/7. (PMID:32721402)
- Posteriorly rotated ears (HP:0000358): A type of abnormal location of the ears in which the position of the ears is characterized by posterior rotation (the superior part of the ears is rotated towards the back of the head, and the inferior part of the ears towards the front). Evidence: PCS. Frequency: 6/7. (PMID:32721402)
- Highly arched eyebrow (HP:0002553): Increased height of the central portion of the eyebrow, forming a crescent, semicircular, or inverted U shape. Evidence: PCS. Frequency: 1/7. (PMID:32721402)
- Downslanted palpebral fissures (HP:0000494): The palpebral fissure inclination is more than two standard deviations below the mean. Evidence: PCS. Frequency: 3/7. (PMID:32721402)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 1/7. (PMID:32721402)
- Generalized hirsutism (HP:0002230): Abnormally increased hair growth over much of the entire body. Evidence: PCS. Frequency: 1/7. (PMID:32721402)
- 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: 1/5. Onset: Childhood onset (HP:0011463). (PMID:32721402)
- 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: 1/7. (PMID:32721402)
- 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: PCS. Frequency: 7/7. (PMID:32721402)
- Microdontia (HP:0000691): Decreased size of the teeth, which can be defined as a mesiodistal tooth diameter (width) more than 2 SD below mean. Alternatively, an apparently decreased maximum width of tooth. Evidence: PCS. Frequency: 1/7. (PMID:32721402)
- Tapered finger (HP:0001182): The gradual reduction in girth of the finger from proximal to distal. Evidence: PCS. Frequency: 2/7. (PMID:32721402)
- Recurrent otitis media (HP:0000403): Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media. Evidence: PCS. Frequency: 2/7. (PMID:32721402)
- Almond-shaped palpebral fissure (HP:0007874): A shape created by an acute downward arching of the upper eyelid and upward arching of the lower eyelid, toward the medial canthus, which gives the outline of the palpebral fissures the configuration of an almond. Thus, the maximum distance between the fissures is offset from, and medial to, the center point. Evidence: PCS. Frequency: 1/7. (PMID:32721402)
- 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: PCS. Frequency: 1/7. (PMID:32721402)
- 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:32721402)
- 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: 3/7. (PMID:32721402)
- Bilateral talipes equinovarus (HP:0001776): Bilateral clubfoot deformity. Evidence: PCS. Frequency: 1/7. (PMID:32721402)
- Widely spaced teeth (HP:0000687): Increased spaces (diastemata) between most of the teeth in the same dental arch. Evidence: PCS. Frequency: 2/7. (PMID:32721402)
- 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: PCS. Frequency: 2/7. (PMID:32721402)
- 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: PCS. Frequency: 1/7. (PMID:32721402)
- Anteverted nares (HP:0000463): Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip). Evidence: PCS. Frequency: 1/7. (PMID:32721402)
- Low posterior hairline (HP:0002162): Hair on the neck extends more inferiorly than usual. Evidence: PCS. Frequency: 4/7. (PMID:32721402)
- Anxiety (HP:0000739): Intense feelings of nervousness, tension, or panic often arise in response to interpersonal stresses. There is worry about the negative effects of past unpleasant experiences and future negative possibilities. Individuals may feel fearful, apprehensive, or threatened by uncertainty, and they may also have fears of falling apart or losing control. Evidence: PCS. Frequency: 1/7. (PMID:32721402)
- Enlarged thorax (HP:0100625). Evidence: PCS. Frequency: 1/7. (PMID:32721402)
- 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: 1/7. (PMID:32721402)
- Clinodactyly (HP:0030084): An angulation of a digit at an interphalangeal joint in the plane of the palm (finger) or sole (toe). Evidence: PCS. Frequency: 1/7. (PMID:32721402)
- 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: 1/7. (PMID:32721402)
- Wide mouth (HP:0000154): Distance between the oral commissures more than 2 SD above the mean. Alternatively, an apparently increased width of the oral aperture (subjective). Evidence: PCS. Frequency: 2/7. (PMID:32721402)
- Typically de novo (HP:0025352): Description of conditions that are exclusively or predominantly observed to display de novo variants. In some cases, this may be due to the limited reproductive fitness of affected individuals. Evidence: PCS. (PMID:32721402)
- 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: PCS. Frequency: 6/7. (PMID:32721402)
- Multiple lentigines (HP:0001003): Presence of an unusually high number of lentigines (singular: lentigo), which are flat, tan to brown oval spots. Evidence: PCS. Frequency: 1/7. (PMID:32721402)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 1/7. (PMID:32721402)
- Wide nasal bridge (HP:0000431): Increased breadth of the nasal bridge (and with it, the nasal root). Evidence: PCS. Frequency: 2/7. (PMID:32721402)
- Prominent metopic ridge (HP:0005487): Vertical bony ridge positioned in the midline of the forehead. Evidence: PCS. Frequency: 2/7. (PMID:32721402)
- Short neck (HP:0000470): Diminished length of the neck. Evidence: PCS. Frequency: 4/7. (PMID:32721402)
- Broad eyebrow (HP:0011229): Regional increase in the width (height) of the eyebrow. Evidence: PCS. Frequency: 1/7. (PMID:32721402)
- Head-banging (HP:0012168): Habitual striking of one's own head against a surface such as a mattress or wall of a crib. Evidence: PCS. Frequency: 1/7. (PMID:32721402)
- Lower limb asymmetry (HP:0100559): A difference in length or diameter between the left and right leg. Evidence: PCS. Frequency: 1/7. (PMID:32721402)
- 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: 6/7. (PMID:32721402)
- High forehead (HP:0000348): An abnormally increased height of the forehead. Evidence: PCS. Frequency: 1/7. (PMID:32721402)
- Pointed chin (HP:0000307): A marked tapering of the lower face to the chin. Evidence: PCS. Frequency: 1/7. (PMID:32721402)
- Cubitus valgus (HP:0002967): Abnormal positioning in which the elbows are turned out. Evidence: PCS. Frequency: 1/7. (PMID:32721402)
- Plagiocephaly (HP:0001357): Asymmetric head shape, which is usually a combination of unilateral occipital flattening with ipsilateral frontal prominence, leading to rhomboid cranial shape. Evidence: PCS. Frequency: 1/7. (PMID:32721402)
- 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: 2/7. (PMID:32721402)
- 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: PCS. Frequency: 3/7. (PMID:32721402)
- 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: 4/7. (PMID:32721402)
- 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: 2/6. (PMID:32721402)
- Micrognathia (HP:0000347): Developmental hypoplasia of the mandible. Evidence: PCS. Frequency: 1/7. (PMID:32721402)
- 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: PCS. Frequency: 2/7. (PMID:32721402)