Joint pain.

Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).

Urge incontinence is the strong, sudden need to urinate.

A developmental defect in which a kidney is located in an abnormal anatomic position within the pelvis.

A unilateral form of agenesis of the kidney.

A uterus that has a single horn, with a banana-like shape that may or may not have a secondary rudimentary uterine horn.

Abnormally small penis. At birth, the normal penis is about 3 cm (stretched length from pubic tubercle to tip of penis) with micropenis less than 2.0-2.5 cm.

A type of knee joint contracture in which the knee is in a fixed bent (flexed) configuration such that it cannot be straightened actively or passively.

The distal and proximal transverse palmar creases are merged into a single transverse palmar crease.

The gradual reduction in girth of the finger from proximal to distal.

A partial dislocation of the hip joint, whereby the head of the femur is partially displaced from the socket.

An outward deviation of the foot at the talocalcaneal or subtalar joint.

Hypoplastic/small middle phalanx of the fifth finger.

Clinodactyly refers to a bending or curvature of the fifth finger in the radial direction (i.e., towards the 4th finger).

Fingers that are disproportionately narrow (reduced girth) for the hand/foot size or build of the individual.

Weakness of the muscles responsible for dorsiflexion of the foot, that is, of the movement of the toes towards the shin. The foot dorsiflexors include the tibialis anterior, the extensor hallucis longus, the extensor digitorum longus, and the peroneus tertius muscles.

Double outlet right ventricle (DORV) is a type of ventriculoarterial connection in which both great vessels arise entirely or predominantly from the right ventricle.

A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum.

Increased pressure in the portal vein.

Critical congenital heart disease (CCHD) is a term that refers to a group of serious heart defects that are present from birth. These abnormalities result from problems with the formation of one or more parts of the heart during the early stages of embryonic development. CCHD prevents the heart from pumping blood effectively or reduces the amount of oxygen in the blood. As a result, organs and tissues throughout the body do not receive enough oxygen, which can lead to organ damage and life-threatening complications. Individuals with CCHD usually require surgery soon after birth.\n\nAlthough babies with CCHD may appear healthy for the first few hours or days of life, signs and symptoms soon become apparent. These can include an abnormal heart sound during a heartbeat (heart murmur), rapid breathing (tachypnea), low blood pressure (hypotension), low levels of oxygen in the blood (hypoxemia), and a blue or purple tint to the skin caused by a shortage of oxygen (cyanosis). If untreated, CCHD can lead to shock, coma, and death. However, most people with CCHD now survive past infancy due to improvements in early detection, diagnosis, and treatment.\n\nSome people with treated CCHD have few related health problems later in life. However, long-term effects of CCHD can include delayed development and reduced stamina during exercise. Adults with these heart defects have an increased risk of abnormal heart rhythms, heart failure, sudden cardiac arrest, stroke, and premature death.\n\nEach of the heart defects associated with CCHD affects the flow of blood into, out of, or through the heart. Some of the heart defects involve structures within the heart itself, such as the two lower chambers of the heart (the ventricles) or the valves that control blood flow through the heart. Others affect the structure of the large blood vessels leading into and out of the heart (including the aorta and pulmonary artery). Still others involve a combination of these structural abnormalities.\n\nPeople with CCHD have one or more specific heart defects. The heart defects classified as CCHD include coarctation of the aorta, double-outlet right ventricle, D-transposition of the great arteries, Ebstein anomaly, hypoplastic left heart syndrome, interrupted aortic arch, pulmonary atresia with intact septum, single ventricle, total anomalous pulmonary venous connection, tetralogy of Fallot, tricuspid atresia, and truncus arteriosus.

Critical congenital heart disease (CCHD) is a term that refers to a group of serious heart defects that are present from birth. These abnormalities result from problems with the formation of one or more parts of the heart during the early stages of embryonic development. CCHD prevents the heart from pumping blood effectively or reduces the amount of oxygen in the blood. As a result, organs and tissues throughout the body do not receive enough oxygen, which can lead to organ damage and life-threatening complications. Individuals with CCHD usually require surgery soon after birth.\n\nAlthough babies with CCHD may appear healthy for the first few hours or days of life, signs and symptoms soon become apparent. These can include an abnormal heart sound during a heartbeat (heart murmur), rapid breathing (tachypnea), low blood pressure (hypotension), low levels of oxygen in the blood (hypoxemia), and a blue or purple tint to the skin caused by a shortage of oxygen (cyanosis). If untreated, CCHD can lead to shock, coma, and death. However, most people with CCHD now survive past infancy due to improvements in early detection, diagnosis, and treatment.\n\nSome people with treated CCHD have few related health problems later in life. However, long-term effects of CCHD can include delayed development and reduced stamina during exercise. Adults with these heart defects have an increased risk of abnormal heart rhythms, heart failure, sudden cardiac arrest, stroke, and premature death.\n\nEach of the heart defects associated with CCHD affects the flow of blood into, out of, or through the heart. Some of the heart defects involve structures within the heart itself, such as the two lower chambers of the heart (the ventricles) or the valves that control blood flow through the heart. Others affect the structure of the large blood vessels leading into and out of the heart (including the aorta and pulmonary artery). Still others involve a combination of these structural abnormalities.\n\nPeople with CCHD have one or more specific heart defects. The heart defects classified as CCHD include coarctation of the aorta, double-outlet right ventricle, D-transposition of the great arteries, Ebstein anomaly, hypoplastic left heart syndrome, interrupted aortic arch, pulmonary atresia with intact septum, single ventricle, total anomalous pulmonary venous connection, tetralogy of Fallot, tricuspid atresia, and truncus arteriosus.

Underdevelopment of the arch of aorta.

Significant luminal narrowing of a long segment of or the entire ascending aorta.

A rare congenital vascular anomaly that results when the left superior cardinal vein caudal to the innominate vein fails to regress.

A fixed form of obstruction to blood flow across the left-ventricular outflow tract related to stenosis (narrowing) below the level of the aortic valve.

A congenital defect with failure to open of the mitral valve orifice.

The trabecular septum is the largest part of the interventricular septum. It extends from the membranous septum to the apex and superiorly to the infundibular septum. A defect in the trabecular septum is called muscular VSD if the defect is completely rimmed by muscle.

Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.

Impairment of bile flow due to obstruction in bile ducts.

Difficulty in swallowing.

Extreme dilation of the submucusoal veins in the lower portion of the esophagus.

Simultaneous enlargement of the liver and spleen.

Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.

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.

An inadequate sucking reflex, resulting in the difficult of newborns to be breast-fed.

Steatosis is a term used to denote lipid accumulation within hepatocytes.

The condition of inability to eat normally treated by placement of a thin tube through the nose into the stomach that is then used to carry food.

Median longitudinal ear length greater than two standard deviations above the mean and median ear width greater than two standard deviations above the mean (objective); or, apparent increase in length and width of the pinna (subjective).

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.

Bruxism is characterized by the grinding of the teeth including the clenching of the jaw and typically occur during sleep, but also can occur while the affected individual is awake.

Cephalgia, or pain sensed in various parts of the head, not confined to the area of distribution of any nerve.

Acting on the spur of the moment in response to immediate stimuli; acting on a momentary basis without a plan or consideration of outcomes; having difficulty establishing or following plans; experiencing a sense of urgency and engaging in self-harming behavior when under emotional distress.

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.

A sudden movement downward, usually resulting in injury.

Abnormality observed by electroencephalogram (EEG), which is used to record of the brain's spontaneous electrical activity from multiple electrodes placed on the scalp.

Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.

Focal impaired awareness seizure (or focal seizure with impaired or lost awareness) is a type of focal-onset seizure characterized by some degree (which may be partial) of impairment of the person's awareness of themselves or their surroundings at any point during the seizure.

Atonic seizure is a type of motor seizure characterized by a sudden loss or diminution of muscle tone without apparent preceding myoclonic or tonic event lasting about 1 to 2 seconds, involving head, trunk, jaw, or limb musculature.

An abnormal gait pattern characterized by the failure of the heel to contact the floor at the onset of stance during gait.

A degree of language development that is significantly below the norm for a child of a specified age.

The feeling of frustration can be defined as an emotional reaction that occurs when a desired goal is not achieved. Frustration intolerance is defined as an age-inappropriate response to frustration, characterized by crying or temper tantrums in children, or aggressive or other undesirable behaviors.

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.

An abnormal gait pattern in which persons stand and walk with their feet spaced widely apart. This is often a component of cerebellar ataxia.

Persistent deficits in social interaction and communication and interaction as well as a markedly restricted repertoire of activity and interest as well as repetitive patterns of behavior.

A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. It is said to be the third leading cause of death in the United States. Gunel and Lifton (1996) noted that about 20% of strokes are hemorrhagic, resulting in bleeding into the brain. Ischemic strokes, resulting from vascular occlusion, account for the majority of strokes. Bersano et al. (2008) reviewed genetic polymorphisms that have been implicated in the development of stroke. Candidate genes include those involved in hemostasis (see, e.g., F5; 612309), the renin-angiotensin-aldosterone system (see, e.g., ACE; 106180), homocysteine (see, e.g., MTHFR; 607093), and lipoprotein metabolism (see, e.g., APOE; 107741). See also hemorrhagic stroke, or intracerebral hemorrhage (ICH; 614519).

An abnormality characterized by disruption of the normal functioning of peripheral axons.

Horner syndrome, resulting from unilateral paralysis of the cervical sympathetics, comprises the classic triad of unilateral ptosis, unilateral miosis with anisocoria, and ipsilateral facial anhidrosis. Iris heterochromia may also be present (Takanashi et al., 2003).

An increase in size of the ventricular system of the brain.

Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.

A mild delay in the achievement of motor or mental milestones in the domains of development of a child.

Delayed myelination in the central nervous system.

An abnormally decreased size of the pituitary gland.

Habitual repetitive movement of the entire body, front to back or side to side.

Areas of brighter than expected signal on magnetic resonance imaging emanating from the cerebral white matter that surrounds the cerebral ventricles.

A type of anemia caused by premature destruction of red blood cells (hemolysis).

A congenital failure of muscular development of part or all of one or both hemidiaphragms, resulting in superior displacement of abdominal viscera and altered lung development.

Protrusion of the contents of the abdominal cavity through the inguinal canal.

Abnormally increased curvature (anterior concavity) of the lumbar or cervical spine.

Developmental hypoplasia of the mandible.

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.

The presence of swelling in a joint.

Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.

An abnormality of skull shape characterized by a decreased anterior-posterior diameter. That is, a cephalic index greater than 81%. Alternatively, an apparently shortened anteroposterior dimension (length) of the head compared to width.

An abnormality of skull shape characterized by a increased anterior-posterior diameter, i.e., an increased antero-posterior dimension of the skull. Cephalic index less than 76%. Alternatively, an apparently increased antero-posterior length of the head compared to width. Often due to premature closure of the sagittal suture.

Dislocation of many joints.

A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.

An elbow contracture that limits the ability of the elbow joint to be extended (straightened), meaning that the elbow is fixed in an flexed (bent) position.

Lack of full passive range of motion (restrictions in flexion, extension, or other movements) of the hip joint resulting from structural changes of non-bony tissues, such as muscles, tendons, ligaments, joint capsules and/or skin.

The ability of the finger joints to move beyond their normal range of motion.

The capability that a joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes.

A reduced amount of fat tissue in the lowest layer of the integument. This feature can be appreciated by a reduced skinfold thickness.

Generalized muscular hypotonia (abnormally low muscle tone).

Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.

Multiple congenital contractures in different body areas.

Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event.

Inspiration of a foreign object into the airway.

Respiratory difficulty as newborn.

Asthma is characterized by increased responsiveness of the tracheobronchial tree to multiple stimuli, leading to narrowing of the air passages with resultant dyspnea, cough, and wheezing.

Atopic dermatitis (ATOD), also known as eczema, is a common chronic pruritic inflammatory skin disease with a strong genetic component. Onset typically occurs during the first 2 years of life (review by Soderhall et al., 2007). Genetic Heterogeneity of Atopic Dermatitis Many inflammatory diseases, such as atopic eczema, are genetically complex, with multiple alleles at several loci thought to be involved in their pathogenesis. Several susceptibility loci for atopic dermatitis have been identified: ATOD1 on chromosome 3q21, ATOD2 (605803) on chromosome 1q21, ATOD3 (605804) on chromosome 20p, ATOD4 (605805) on chromosome 17q25.3, ATOD5 (603165) on chromosome 13q12-q14, ATOD6 (605845) on chromosome 5q31-q33, ATOD7 (613064) on chromosome 11q13.5, ATOD8 (613518) on chromosome 4q22.1, and ATOD9 (613519) on chromosome 3p24.

Chronic otitis media refers to fluid, swelling, or infection of the middle ear that does not heal and may cause permanent damage to the ear.

Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media.

An abnormally decreased calcium concentration in the blood.

An abnormally decreased magnesium concentration in the blood.

Developmental hypoplasia of the dental enamel.

Distance between the oral commissures more than 2 SD above the mean. Alternatively, an apparently increased width of the oral aperture (subjective).

Distance between the commissures of the mouth more than 2 SD below the mean. Alternatively, an apparently decreased width of the oral aperture (subjective).

Changes in alignment of teeth in the dental arch

Delayed tooth eruption, which can be defined as tooth eruption more than 2 SD beyond the mean eruption age.

An abnormally increased height of the forehead.

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).

Abnormal prominence of the chin related to increased length of the mandible.

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.

Distance between the inner canthi more than two standard deviations above the mean (objective); or, apparently increased distance between the inner canthi.

Distance between subnasale and pronasale more than two standard deviations above the mean, or alternatively, an apparently increased anterior protrusion of the nasal tip.

Cleft of the soft palate (also known as the velum, or muscular palate) as a result of a developmental defect occurring between the 7th and 12th week of pregnancy. Cleft soft palate can cause functional abnormalities of the Eustachian tube with resulting middle ear anomalies and hearing difficulties, as well as speech problems associated with hypernasal speech due to velopharyngeal insufficiency.

A congenital defect characterized by the absence of one or more permanent teeth, including oligodontia, hypodontia, and adontia of the of permanent teeth.

Posterior positioning of the nasal root in relation to the overall facial profile for age.

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).

Accentuated, prominent philtral ridges giving rise to an exaggerated groove in the midline between the nasal base and upper vermillion border.

An abnormal distribution of eyebrow hair growth in the medial direction.

Distance between medial and lateral canthi is more than two standard deviations above the mean for age (objective); or, apparently increased length of the palpebral fissures.

Increased density/number and/or increased diameter of eyebrow hairs.

Distance from nasion to subnasale more than two standard deviations below the mean, or alternatively, an apparently decreased length from the nasal root to the nasal tip.

Decreased number of hairs per unit area of skin of the scalp.

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).

A morphological abnormality of the mouth in which the angle of the mouth is downturned. The oral commissures are positioned inferior to the midline labial fissure.

Increased prominence or roundness of soft tissues between zygomata and mandible.

Exaggerated bulkiness of the crease or fold of skin running from the lateral margin of the nose, where nasal base meets the skin of the face, to a point just lateral to the corner of the mouth (cheilion, or commissure).

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.

An eyebrow that extends straight across the brow, without curve.

Wrinkled, redundant, inelastic and sagging skin.

Abnormally increased hair growth referring to a male pattern of body hair (androgenic hair).

An abnormality of the skin characterized the presence of excessive amounts of dry surface scales on the skin resulting from an abnormality of keratinization.

Redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin.

Raised, well-circumscribed areas of erythema and edema involving the dermis and epidermis. Urticaria is intensely pruritic, and blanches completely with pressure.

Skin characterized by the lack of natural or normal moisture.

Refers to the loss of the outer layer of the epidermis in large, scale-like flakes.

Redness of the skin of the face, caused by hyperemia of the capillaries in the lower layers of the skin.

An anomaly of the hair follicles of the skin that typically presents as small, rough, brown folliculocentric papules distributed over characteristic areas of the skin, particularly the outer-upper arms and thighs.

A cutaneous indentation resulting from tethering of the skin to underlying structures (bone) of the intergluteal cleft.

Meeting of the medial eyebrows in the midline.

Mid upper eyelash length >10 mm or increased length of the eyelashes (subjective).

Excessive, increased hair growth located in the thoracic region.

The presence of two to five cafe-au-lait macules.

Diminished amniotic fluid volume in pregnancy.

An abnormal reduction in quantity or strength of fetal movements.

Accumulation of fluid in the peritoneal cavity during the fetal period.

Single umbilical artery (SUA) is the absence of one of the two umbilical arteries surrounding the fetal bladder and in the fetal umbilical cord.

Echogenic bowel is defined as fetal bowel with homogenous areas of echogenicity that are equal to or greater than that of surrounding bone.

Developmental hypoplasia of the thyroid gland.

Insufficient responses to growth hormone (GH) provocation tests. GH deficiency is defined as a serum peak GH concentration less than 10 ng/mL on provocation with a combination of at least two separate stimulation tests.

A larger than usual distance between the left and right nipple.

A form of strabismus with one or both eyes deviated outward.

An abnormality of refraction characterized by the ability to see objects in the distance clearly, while objects nearby appear blurry.

An eye that is more deeply recessed into the plane of the face than is typical.

Interpupillary distance less than 2 SD below the mean (alternatively, the appearance of an decreased interpupillary distance or closely spaced eyes).

An abnormal bluish coloration of the sclera.