Phenotypes associated with the disease Noonan syndrome-like disorder with loose anagen hair 2 (OMIM:617506):
- 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: 1/4. (PMID:27264673)
- 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: 4/5. (PMID:27264673;PMID:27868344)
- Dermal translucency (HP:0010648): An abnormally increased ability of the skin to permit light to pass through (translucency) such that subcutaneous structures such as veins display an increased degree of visibility. Evidence: PCS. Frequency: 1/8. (PMID:27681385)
- 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: PCS. Frequency: 6/12. (PMID:27681385;PMID:27264673)
- Relative macrocephaly (HP:0004482): A relatively mild degree of macrocephaly in which the head circumference is not above two standard deviations from the mean, but appears dysproportionately large when other factors such as body stature are taken into account. Evidence: PCS. Frequency: 3/4. (PMID:27264673)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: PCS. Frequency: 2/4. (PMID:27264673)
- Hypoplastic aortic arch (HP:0012304): Underdevelopment of the arch of aorta. Evidence: PCS. Frequency: 1/8. (PMID:27681385)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: PCS. Frequency: 1/4. (PMID:27264673)
- Smooth philtrum (HP:0000319): Flat skin surface, with no ridge formation in the central region of the upper lip between the nasal base and upper vermilion border. Evidence: PCS. Frequency: 1/8. (PMID:27681385)
- 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: 1/4. (PMID:27264673)
- Prominent forehead (HP:0011220): Forward prominence of the entire forehead, due to protrusion of the frontal bone. Evidence: PCS. Frequency: 3/8. (PMID:27681385)
- Fetal onset (HP:0011461): Onset prior to birth but after 8 weeks of embryonic development (corresponding to a gestational age of 10 weeks). Evidence: PCS. Frequency: 1/1. (PMID:27868344)
- 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: 9/14. (PMID:27681385;PMID:28211982;PMID:27264673;PMID:27868344)
- Aortic root aneurysm (HP:0002616): An abnormal localized widening (dilatation) of the aortic root. Evidence: PCS. Frequency: 1/8. (PMID:27681385)
- 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: TAS. (OMIM:617506)
- Slow-growing hair (HP:0002217): Hair whose growth is slower than normal. Evidence: PCS. Frequency: 6/13. (PMID:27681385;PMID:27264673;PMID:27868344)
- 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: 1/3. (PMID:27264673)
- 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: 8/14. (PMID:27681385;PMID:28211982;PMID:27264673;PMID:27868344)
- 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: 1/8. (PMID:27681385)
- Downslanted palpebral fissures (HP:0000494): The palpebral fissure inclination is more than two standard deviations below the mean. Evidence: PCS. Frequency: 5/14. (PMID:27681385;PMID:28211982;PMID:27264673;PMID:27868344)
- Delayed skeletal maturation (HP:0002750): A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body. Evidence: PCS. Frequency: 3/6. (PMID:27681385)
- 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: 4/8. (PMID:27681385)
- Feeding difficulties (HP:0011968): Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it. Evidence: PCS. Frequency: 3/4. (PMID:27264673)
- 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: 18/18. (PMID:27681385;PMID:28211982;PMID:27264673;PMID:27868344)
- Tricuspid regurgitation (HP:0005180): Failure of the tricuspid valve to close sufficiently upon contraction of the right ventricle, causing blood to regurgitate (flow backward) into the right atrium. Evidence: PCS. Frequency: 1/8. (PMID:27681385)
- Optic nerve hypoplasia (HP:0000609): Underdevelopment of the optic nerve. Evidence: PCS. Frequency: 1/4. (PMID:27264673)
- High anterior hairline (HP:0009890): Distance between the hairline (trichion) and the glabella (the most prominent point on the frontal bone above the root of the nose), in the midline, more than two SD above the mean. Alternatively, an apparently increased distance between the hairline and the glabella. Evidence: PCS. Frequency: 1/8. (PMID:27681385)
- 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: 4/7. (PMID:27681385;PMID:27868344)
- Peripheral pulmonary artery stenosis (HP:0004969): Stenosis of a peripheral branch of the pulmonary artery. Evidence: PCS. Frequency: 1/7. (PMID:27681385)
- Facial hemangioma (HP:0000329): Hemangioma, a benign tumor of the vascular endothelial cells, occurring in the face. Evidence: PCS. Frequency: 1/4. (PMID:27264673)
- Triangular mouth (HP:0000207): The presence of a triangular form of the mouth. Evidence: PCS. Frequency: 2/8. (PMID:27681385)
- 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: 1/1. (PMID:28211982)
- 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: 1/8. (PMID:27681385)
- Lacrimal duct stenosis (HP:0007678): Narrowing of a tear duct (lacrimal duct). Evidence: PCS. Frequency: 1/4. (PMID:27264673)
- Thin skin (HP:0000963): Reduction in thickness of the skin, generally associated with a loss of suppleness and elasticity of the skin. Evidence: PCS. Frequency: 2/8. (PMID:27681385)
- 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: 6/12. (PMID:27681385;PMID:27264673)
- 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:27264673)
- Wide nose (HP:0000445): Interalar distance more than two standard deviations above the mean for age, i.e., an apparently increased width of the nasal base and alae. Evidence: PCS. Frequency: 2/8. (PMID:27681385)
- Widely spaced teeth (HP:0000687): Increased spaces (diastemata) between most of the teeth in the same dental arch. Evidence: PCS. Frequency: 1/8. (PMID:27681385)
- Sparse lateral eyebrow (HP:0005338): Decreased density/number and/or decreased diameter of lateral eyebrow hairs. Evidence: PCS. Frequency: 1/1. (PMID:28211982)
- 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: PCS. Frequency: 4/9. (PMID:27681385;PMID:28211982;PMID:27868344)
- 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: 1/1. (PMID:28211982)
- Upslanted palpebral fissure (HP:0000582): The palpebral fissure inclination is more than two standard deviations above the mean for age (objective); or, the inclination of the palpebral fissure is greater than typical for age. Evidence: PCS. Frequency: 1/8. (PMID:27681385)
- Preauricular pit (HP:0004467): Small indentation anterior to the insertion of the ear. Evidence: PCS. Frequency: 1/8. (PMID:27681385)
- Congenital onset (HP:0003577): A phenotypic abnormality that is present at birth. Evidence: PCS. (PMID:27681385)
- 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: 1/8. (PMID:27681385)
- Deep philtrum (HP:0002002): Accentuated, prominent philtral ridges giving rise to an exaggerated groove in the midline between the nasal base and upper vermillion border. Evidence: PCS. Frequency: 1/1. (PMID:28211982)
- Low posterior hairline (HP:0002162): Hair on the neck extends more inferiorly than usual. Evidence: PCS. Frequency: 1/8. (PMID:27681385)
- Complete right bundle branch block (HP:0011712): A conduction block of the right branch of the bundle of His. This manifests as a prolongation of the QRS complex (greater than 0.12 s) with delayed activation of the right ventricle and terminal delay on the EKG. Evidence: PCS. Frequency: 1/3. (PMID:27264673)
- Sparse hair (HP:0008070): Reduced density of hairs. Evidence: PCS. Frequency: 1/1. (PMID:28211982)
- 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: 1/1. Onset: Congenital onset (HP:0003577). (PMID:27868344)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. Frequency: 6/8. (PMID:27681385)
- Chronic constipation (HP:0012450): Constipation for longer than three months with fewer than 3 bowel movements per week, straining, lumpy or hard stools, and a sensation of anorectal obstruction or incomplete defecation. Evidence: PCS. Frequency: 2/8. (PMID:27681385)
- 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: 2/4. (PMID:27264673)
- 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: 3/4. (PMID:27264673)
- Dandy-Walker malformation (HP:0001305): A congenital brain malformation typically characterized by incomplete formation of the cerebellar vermis, dilation of the fourth ventricle, and enlargement of the posterior fossa. In layman's terms, Dandy Walker malformation is a cyst in the cerebellum (typically symmetrical) that is involved with the fourth ventricle. This may interfere with the ability to drain cerebrospinal fluid from the brain, resulting in hydrocephalus. Dandy Walker cysts are formed during early embryonic development, while the brain forms. The cyst in the cerebellum typically has several blood vessels running through it connecting to the brain, thereby prohibiting surgical removal. Evidence: PCS. Frequency: 1/3. (PMID:27264673)
- Thin upper lip vermilion (HP:0000219): Height of the vermilion of the upper lip in the midline more than 2 SD below the mean. Alternatively, an apparently reduced height of the vermilion of the upper lip in the frontal view (subjective). Evidence: PCS. Frequency: 3/8. (PMID:27681385)
- 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: 3/8. (PMID:27681385)
- Wide intermamillary distance (HP:0006610): A larger than usual distance between the left and right nipple. Evidence: PCS. Frequency: 1/1. (PMID:27868344)
- 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: 4/4. (PMID:27264673)
- Overfolded helix (HP:0000396): A condition in which the helix is folded over to a greater degree than normal. That is, excessive curling of the helix edge, whereby the free edge is parallel to the plane of the ear. Evidence: PCS. Frequency: 1/8. (PMID:27681385)
- Curly hair (HP:0002212). Evidence: PCS. Frequency: 1/4. (PMID:27264673)
- Polyhydramnios (HP:0001561): The presence of excess amniotic fluid in the uterus during pregnancy. Evidence: PCS. Frequency: 1/1. (PMID:27868344)
- Craniosynostosis (HP:0001363): Craniosynostosis refers to the premature closure of the cranial sutures. Primary craniosynostosis refers to the closure of one or more sutures due to abnormalities in skull development, and secondary craniosynostosis results from failure of brain growth. Evidence: PCS. Frequency: 1/1. (PMID:28211982)
- Scoliosis (HP:0002650): The presence of an abnormal lateral curvature of the spine. Evidence: PCS. Frequency: 1/1. (PMID:28211982)
- 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: 8/8. (PMID:27681385)
- Broad neck (HP:0000475): Increased side-to-side width of the neck. Evidence: PCS. Frequency: 2/9. (PMID:27681385;PMID:27868344)
- Underdeveloped nasal alae (HP:0000430): Thinned, deficient, or excessively arched ala nasi. Evidence: PCS. Frequency: 1/8. (PMID:27681385)
- Thickened helices (HP:0000391): Increased thickness of the helix of the ear. Evidence: PCS. Frequency: 1/8. (PMID:27681385)
- 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: 1/4. (PMID:27264673)
- Bifid uvula (HP:0000193): Uvula separated into two parts most easily seen at the tip. Evidence: PCS. Frequency: 1/8. (PMID:27681385)
- Short neck (HP:0000470): Diminished length of the neck. Evidence: PCS. Frequency: 2/5. (PMID:27264673;PMID:27868344)
- Coarctation of aorta (HP:0001680): Coarctation of the aorta is a narrowing or constriction of a segment of the aorta. Evidence: PCS. Frequency: 4/16. (PMID:27681385)
- 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: 0/3. (PMID:27264673)
- 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: PCS. Frequency: 1/4. (PMID:27264673)
- 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: 2/9. (PMID:27681385;PMID:27868344)
- High forehead (HP:0000348): An abnormally increased height of the forehead. Evidence: PCS. Frequency: 1/1. (PMID:28211982)
- Coarse hair (HP:0002208): Hair shafts are rough in texture. Evidence: PCS. Frequency: 1/1. (PMID:27868344)
- Frontal bossing (HP:0002007): Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline. Evidence: PCS. Frequency: 1/8. (PMID:27681385)
- 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: 2/9. (PMID:27681385;PMID:28211982)
- 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: 1/7. (PMID:27681385)
- 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: 1/2. (PMID:27264673)