Persistent pain, usually defined as pain that has lasted longer than 3 to 6 months.

A benign tumor of the parathyroid gland that can cause hyperparathyroidism.

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).

Severe distention of the kidney with dilation of the renal pelvis and calices.

Nephrocalcinosis is the deposition of calcium salts in renal parenchyma.

A connection of the right and left kidney by an isthmus of functioning renal parenchyma or fibrous tissue that crosses the midline.

The presence of calculi (stones) in the kidneys.

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.

Lateral deviation of the great toe (i.e., in the direction of the little toe).

Broadening of the soft tissues (non-edematous swelling of soft tissues) of the digital tips in all dimensions associated with an increased longitudinal and lateral curvature of the nails.

Polydactyly refers to the occurrence of supernumerary digits and is the most frequent of congenital hand and foot deformities. Based on the location of the extra digits, polydactyly can be classified into preaxial, involving the thumb or great toe; postaxial, affecting the fifth digit; and central, involving the 3 central digits. Postaxial polydactyly (PAP) is further subclassified into 2 types: in type A, a well-formed extra digit articulates with the fifth or a sixth metacarpal, whereas in type B, a rudimentary, poorly developed extra digit is present (summary by Umm-e-Kalsoom et al., 2012). Genetic Heterogeneity of Postaxial Polydactyly Other forms of postaxial polydactyly type A include PAPA2 (602085) on chromosome 13q21; PAPA3 (607324) on chromosome 19p13; PAPA4 (608562) on chromosome 7q22; PAPA5 (263450) on chromosome 13q13; PAPA6 (615226), caused by mutation in the ZNF141 gene (194648) on chromosome 4p16; PAPA7 (617642), caused by mutation in the IQCE gene (617631) on chromosome 7p22; PAPA8 (618123), caused by mutation in the GLI1 gene (165220) on chromosome 12q13; PAPA9 (618219), caused by mutation in the CIBAR1 gene (617273) on chromosome 8q22; and PAPA10 (618498), caused by mutation in the KIAA0825 gene (617266) on chromosome 5q15.

Webbing or fusion of the fingers, involving soft parts only or including bone structure. Bony fusions are referred to as "bony" Syndactyly if the fusion occurs in a radio-ulnar axis. Fusions of bones of the fingers in a proximo-distal axis are referred to as "Symphalangism".

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.

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.

A toe that appears disproportionately short compared to the foot.

A measured foot length that is more than 2 SD below the mean for a newborn of 27 - 41 weeks gestation, or foot that is less than the 3rd centile for individuals from birth to 16 years of age (objective). Alternatively, a foot that appears disproportionately short (subjective).

Excessively deep creases of the palm.

Significant reduction in both length and girth of the toe compared to the contralateral toe, or alternatively, compared to a typical toe size for an age-matched individual.

The metatarsals are deviated medially (tibially), that is, the bones in the front half of the foot bend or turn in toward the body.

An angulation of a digit at an interphalangeal joint in the plane of the palm (finger) or sole (toe).

Coarctation of the aorta is a narrowing or constriction of a segment of the aorta.

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.

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.

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

Hemorrhage occurring between the dura mater and the arachnoid mater.

The presence of chronic increased pressure in the systemic arterial system.

Aortic valve disease-2 (AOVD2) is characterized by bicuspid aortic valve (BAV) and dilation of the ascending aorta. Calcification of the valve and the aorta has been observed, and some patients exhibit coarctation of the aorta (Tan et al., 2012; Luyckx et al., 2019; Park et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of aortic valve disease, see AOVD1 (109730).

Mesocardia is an abnormal location of the heart in which the heart is in a midline position and the longitudinal axis of the heart lies in the mid-sagittal plane.

An abnormal localized widening (dilatation) of the aortic root.

Increased dimensions of the Virchow-Robin spaces (also known as perivascular spaces), which surround the walls of vessels as they course from the subarachnoid space through the brain parenchyma. Perivascular spaces are commonly microscopic, and not visible on conventional neuroimaging. This term refers to an increase of size of these spaces such that they are visible on neuroimaging (usually magnetic resonance imaging). The dilatations are regular cavities that always contain a patent artery.

Hemorrhage into the parenchyma of the brain.

The term large for gestational age applies to babies whose birth weight lies above the 90th percentile for that gestational age.

Infrequent or difficult evacuation of feces.

Difficulty in swallowing.

Inflammation of the esophagus.

Protrusion of the rectal mucous membrane through the anus.

Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.

Decreased strength of the muscle layer of stomach, which leads to a decreased ability to empty the contents of the stomach despite the absence of obstruction.

A benign tumor of the liver of presumably epithelial origin.

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

Pyloric stenosis, also known as infantile hypertrophic pyloric stenosis, is an uncommon condition in infants characterized by abnormal thickening of the pylorus muscles in the stomach leading to gastric outlet obstruction. Clinically infants are well at birth. Then, at 3 to 6 weeks of age, the infants present with projectile vomiting, potentially leading to dehydration and weight loss.

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

An abnormality of vibrational conductance of sound to the inner ear leading to impairment of sensory perception of sound.

A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.

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.

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).

An asymmetriy, i.e., difference in size, shape or position between the left and right ear.

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.

Increased thickness of the helix of the ear.

Increased volume of the earlobe, that is, abnormally prominent ear lobules.

Laterally protruding ear that lacks antihelical folding (including absence of inferior and superior crura).

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).

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.

Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996; Risch et al., 1999). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (see ASPG1; 608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008). Genetic studies in autism often include family members with these less stringent diagnoses (Schellenberg et al., 2006). Levy et al. (2009) provided a general review of autism and autism spectrum disorder, including epidemiology, characteristics of the disorder, diagnosis, neurobiologic hypotheses for the etiology, genetics, and treatment options. Genetic Heterogeneity of Autism Autism is considered to be a complex multifactorial disorder involving many genes. Accordingly, several loci have been identified, some or all of which may contribute to the phenotype. Included in this entry is AUTS1, which has been mapped to chromosome 7q22. Other susceptibility loci include AUTS3 (608049), which maps to chromosome 13q14; AUTS4 (608636), which maps to chromosome 15q11; AUTS6 (609378), which maps to chromosome 17q11; AUTS7 (610676), which maps to chromosome 17q21; AUTS8 (607373), which maps to chromosome 3q25-q27; AUTS9 (611015), which maps to chromosome 7q31; AUTS10 (611016), which maps to chromosome 7q36; AUTS11 (610836), which maps to chromosome 1q41; AUTS12 (610838), which maps to chromosome 21p13-q11; AUTS13 (610908), which maps to chromosome 12q14; AUTS14A (611913), which has been found in patients with a deletion of a region of 16p11.2; AUTS14B (614671), which has been found in patients with a duplication of a region of 16p11.2; AUTS15 (612100), associated with mutation in the CNTNAP2 gene (604569) on chromosome 7q35-q36; AUTS16 (613410), associated with mutation in the SLC9A9 gene (608396) on chromosome 3q24; AUTS17 (613436), associated with mutation in the SHANK2 gene (603290) on chromosome 11q13; AUTS18 (615032), associated with mutation in the CHD8 gene (610528) on chromosome 14q11; AUTS19 (615091), associated with mutation in the EIF4E gene (133440) on chromosome 4q23; and AUTS20 (618830), associated with mutation in the NLGN1 gene (600568) on chromosome 3q26. (NOTE: the symbol 'AUTS2' has been used to refer to a gene on chromosome 7q11 (KIAA0442; 607270) and therefore is not used as a part of this autism locus series.) There are several X-linked forms of autism susceptibility: AUTSX1 (300425), associated with mutations in the NLGN3 gene (300336); AUTSX2 (300495), associated with mutations in NLGN4 (300427); AUTSX3 (300496), associated with mutations in MECP2 (300005); AUTSX4 (300830), associated with variation in the region on chromosome Xp22.11 containing the PTCHD1 gene (300828); AUTSX5 (300847), associated with mutations in the RPL10 gene (312173); and AUTSX6 (300872), associated with mutation in the TMLHE gene (300777). A locus on chromosome 2q (606053) associated with a phenotype including intellectual disability and speech deficits was formerly designated AUTS5. Folstein and Rosen-Sheidley (2001) reviewed the genetics of autism.

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.

Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior.

Persistent or frequent inner feelings of anger, irritability, or resentment that may be in response to an action or statement by others that is perceived to be a slight or challenge to the person regardless of the nature. Anger may also occur or arise spontaneously in the absence of any provocation and can be directed to another person or social entity.

A neurological anomaly with gross overeating associated with an abnormally strong desire or need to eat.

Periventricular leukomalacia is characterized by diffuse injury of deep cerebral white matter, accompanied in its most severe form by focal necrosis. The neuropathologic hallmarks of PVL are microglial activation and focal and diffuse periventricular depletion of premyelinating oligodendroglia.

Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.

Moderate mental retardation is defined as an intelligence quotient (IQ) in the range of 35-49.

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.

Severe mental retardation is defined as an intelligence quotient (IQ) in the range of 20-34.

Deep, noisy breathing during sleep, accompanied by hoarse or harsh sounds, is caused by the vibration of respiratory structures, especially the soft palate. This vibration results in sound due to obstructed air movement during breathing while sleeping.

Hemorrhage occurring between the arachnoid mater and the pia mater.

An extra-parenchymal and intra-arachnoidal collection of fluid with a composition similar to that of cerebrospinal fluid.

A state of excessive motor activity that is associated with mental distress or a feeling of substantial unease or inner tension. Distinguished from restlessness by the increased level of emotional distress and negative intensity of the experience. Agitation has a significant level of physical activity that is typically threatening to the self or others.

Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.

A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months.

A cyst occurring within the choroid plexus within a cerebral ventricle.

Underdevelopment of the corpus callosum.

Involuntary contractions of muscle leading to involuntary movements of extremities, neck, trunk, or face.

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

Obstructive sleep apnea is a common, chronic, complex disease associated with serious cardiovascular and neuropsychologic sequelae and with substantial social and economic costs (Palmer et al., 2003).

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.

Accumulation of cerebral spinal fluid in the subdural space.

Attention-deficit/hyperactivity disorder (ADHD) is a behavioral disorder that typically begins in childhood and is characterized by a short attention span (inattention), an inability to be calm and stay still (hyperactivity), and poor impulse control (impulsivity). Some people with ADHD have problems with only inattention or with hyperactivity and impulsivity, but most have problems related to all three features.\n\nIn people with ADHD, the characteristic behaviors are frequent and severe enough to interfere with the activities of daily living such as school, work, and relationships with others. Because of an inability to stay focused on tasks, people with inattention may be easily distracted, forgetful, avoid tasks that require sustained attention, have difficulty organizing tasks, or frequently lose items.\n\nHyperactivity is usually shown by frequent movement. Individuals with this feature often fidget or tap their foot when seated, leave their seat when it is inappropriate to do so (such as in the classroom), or talk a lot and interrupt others.\n\nImpulsivity can result in hasty actions without thought for the consequences. Individuals with poor impulse control may have difficulty waiting for their turn, deferring to others, or considering their actions before acting.\n\nMore than two-thirds of all individuals with ADHD have additional conditions, including insomnia, mood or anxiety disorders, learning disorders, or substance use disorders. Affected individuals may also have autism spectrum disorder, which is characterized by impaired communication and social interaction, or Tourette syndrome, which is a disorder characterized by repetitive and involuntary movements or noises called tics.\n\nIn most affected individuals, ADHD continues throughout life, but in about one-third of individuals, signs and symptoms of ADHD go away by adulthood.

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.

Delayed myelination in the central nervous system.

An abnormally decreased size of the pituitary gland.

A type of motor delay characterized by a delay in acquiring the ability to control the fingers and hands.

A generalized non-motor (absence) seizure is a type of a type of dialeptic seizure that is of electrographically generalized onset. It is a generalized seizure characterized by an interruption of activities, a blank stare, and usually the person will be unresponsive when spoken to. Any ictal motor phenomena are minor in comparison to these non-motor features.

Displacement or malalignment of joints.

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

Protrusion of abdominal contents through a defect in the abdominal wall musculature around the umbilicus. Skin and subcutaneous tissue overlie the defect.

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.

Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5.

An abnormality in which the mandible is mislocalised posteriorly.

The presence of an abnormal lateral curvature of the spine.

Spondylolisthesis is defined as forward slipping of a vertebral body on the one below it. Spondylolysis is defined as a defect in the pars interarticularis without vertebral slipping (summary by Wiltse et al., 1975).

Spondylolysis is an osseous defect of the pars interarticularis, thought to be a developmental or acquired stress fracture secondary to chronic low-grade trauma.

A deformity of the chest caused by overgrowth of the ribs and characterized by protrusion of the sternum.

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

A developmental defect of the sacrum characterized by partial or disordered development of the sacrum in which portions of the sacrum, which normally is formed by fusion of five sacral vertebrae S1-S5, fail to form or fail to form normally.

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.

An irregular surface of the vertebral end plates, which are normally relatively smooth.

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

A flattened vertebral body shape with reduced distance between the vertebral endplates.

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

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.

Increase in size of the cisterna magna, one of three principal openings in the subarachnoid space between the arachnoid and pia mater, located between the cerebellum and the dorsal surface of the medulla oblongata.

Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.

An abnormal narrowing of the spinal canal.

Enlargement of the anterior fontanelle with respect to age-dependent norms.

A defect of the chest wall characterized by a depression of the sternum, giving the chest ("pectus") a caved-in ("excavatum") appearance.

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

A delay in closure (ossification) of the anterior fontanelle, which generally undergoes closure around the 18th month of life.

Congenital dysplasia of the hip (CDH) is an abnormality of the seating of the femoral head in the acetabulum. Its severity ranges from mild instability of the femoral head with slight capsular laxity, through moderate lateral displacement of the femoral head, without loss of contact of the head with the acetabulum, up to complete dislocation of the femoral head from the acetabulum. It is one of the most common skeletal congenital anomalies (summary by Sollazzo et al., 2000). Acetabular dysplasia is an idiopathic, localized developmental dysplasia of the hip that is characterized by a shallow hip socket and decreased coverage of the femoral head. Its radiologic criteria include the center-edge angle of Wiberg, the Sharp angle, and the acetabular roof obliquity. Most patients with acetabular dysplasia develop osteoarthritis (165720) after midlife, and even mild acetabular dysplasia can cause hip osteoarthritis (summary by Mabuchi et al., 2006). CDH occurs as an isolated anomaly or with more general disorders represented by several syndromes and with chromosomal abnormalities such as trisomy 18 (Wynne-Davies, 1970). Genetic Heterogeneity of Developmental Dysplasia of the Hip Developmental dysplasia of the hip-1 (DDH1) maps to chromosome 13q22; DDH2 (615612) maps to chromosome 3p21. DDH3 (620690) is caused by mutation in the LRP1 gene (107770) on chromosome 12q13.

Tall head relative to width and length.

Dryness of the eye related to deficiency of the tear film components (aqueous, mucin, or lipid), lid surface abnormalities, or epithelial abnormalities. Keratoconjunctivitis sicca often results in a scratchy or sandy sensation (foreign body sensation) in the eyes, and may also be associated with itching, inability to produce tears, photosensitivity, redness, pain, and difficulty in moving the eyelids.

An abnormally increased calcium concentration in the blood.

A fixed reduction in the vertical distance between the upper and lower eyelids with short palpebral fissures.

An outward turning (eversion) or rotation of the eyelid margin.

Increased length and width of the tongue.

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

Pierre Robin sequence is a craniofacial anomaly comprising mandibular hypoplasia, cleft secondary palate, and glossoptosis leading to life-threatening obstructive apnea and feeding difficulties during the neonatal period (summary by Tan et al., 2013).

Changes in alignment of teeth in the dental arch

The presence of one or more teeth additional to the normal number.

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

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.

Increased volume and globular shape of the anteroinferior aspect of the nose.

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).

Tongue extending beyond the alveolar ridges or teeth at rest.

Persistence of the primary teeth beyond the age by which they normally are shed and replaced by the permanent teeth.

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.

The palpebral fissure inclination is more than two standard deviations below the mean.

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.

Increase in width of the nasal tip.

Increased aperture of the nostril.

Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).

Flat skin surface, with no ridge formation in the central region of the upper lip between the nasal base and upper vermilion border.

Width of the palate more than 2 SD below the mean (objective) or apparently decreased palatal width (subjective).

Facial height (length) is more than 2 standard deviations above the mean (objective); or, an apparent increase in the height (length) of the face (subjective).

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

Forward prominence of the entire forehead, due to protrusion of the frontal bone.

Bizygomatic (upper face) and bigonial (lower face) width are both more than 2 standard deviations below the mean (objective); or, an apparent reduction in the width of the upper and lower face (subjective).

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).

Distance from nasion to subnasale more than two standard deviations above the mean, or alternatively, an apparently increased length from the nasal root to the nasal base.

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 below the mean. Alternatively, an apparently decreased distance between the hairline and the glabella.

A marked tapering of the lower face to the chin.

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.

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.

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.

Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle.

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

Increased side-to-side width of the neck.

Hair on the neck extends more inferiorly than usual.

Columella extending inferior to the level of the nasal base, when viewed from the side.

Regional increase in the width (height) of the eyebrow.

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.

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).

Increased height of the central portion of the eyebrow, forming a crescent, semicircular, or inverted U shape.

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).

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.

Increase in periorbital soft tissue.

Hypertrichosis is increased hair growth that is abnormal in quantity or location.

A nail that is diminished in length and width, i.e., underdeveloped nail.

Aplasia cutis congenita (ACC) is defined as congenital localized absence of skin. The skin appears as a thin, transparent membrane through which the underlying structures are visible. The location is usually on the scalp (Evers et al., 1995). Approximately 20 to 30% of cases have underlying osseous involvement (Elliott and Teebi, 1997). Autosomal dominant inheritance is most common, but recessive inheritance has also been reported. Cutaneous aplasia of the scalp vertex also occurs in Johanson-Blizzard syndrome (243800) and Adams-Oliver syndrome (AOS; 100300). A defect in the scalp is sometimes found in cases of trisomy 13 and in about 15% of cases of deletion of the short arm of chromosome 4, the Wolf-Hirschhorn syndrome (WHS; 194190) (Hirschhorn et al., 1965; Fryns et al., 1973). Evers et al. (1995) provided a list of disorders associated with aplasia cutis congenita, classified according to etiology. They also tabulated points of particular significance in history taking and examination of patients with ACC.

Hair that is fine or thin to the touch.

Meeting of the medial eyebrows in the midline.

Hair whose growth is slower than normal.

A lesser degree of hair pigmentation than would otherwise be expected.

A rudimentary tag of skin often containing ear tissue including a core of cartilage and located just anterior to the auricle (outer part of the ear).

Deeply placed nails.

Eyelashes that draw the attention of the viewer due to increased density and/or length and/or curl without meeting the criteria of trichomegaly.

Increased density of hairs, i.e., and elevated number of hairs per unit area.

Absence of melanin pigment in various areas, which is found at birth and is permanent. The lesions are known as leucoderma and are often found on the face, trunk, or limbs.

Delivery of a fetus through surgical incisions made through the abdominal wall (laparotomy) and the uterine wall (hysterotomy).

The presence of excess amniotic fluid in the uterus during pregnancy.

Diminished amniotic fluid volume in pregnancy.

The birth of a baby of less than 37 weeks of gestational age.

Excessive production of parathyroid hormone (PTH) by the parathyroid glands.

Deficiency of thyroid hormone.

Passing the age when puberty normally occurs with no physical or hormonal signs of the onset of puberty.

Hypogonadotropic hypogonadism is characterized by reduced function of the gonads (testes in males or ovaries in females) and results from the absence of the gonadal stimulating pituitary hormones

Reduced visual acuity that is uncorrectable by lenses in the absence of detectable anatomic defects in the eye or visual pathways.

Astigmatism (from the Greek 'a' meaning absence and 'stigma' meaning point) is a condition in which the parallel rays of light entering the eye through the refractive media are not focused on a single point. Both corneal and noncorneal factors contribute to refractive astigmatism. Corneal astigmatism is mainly the result of an aspheric anterior surface of the cornea, which can be measured readily by means of a keratometer; in a small fraction of cases (approximately 1 in 10) the effect is neutralized by the back surface. The curvature of the back surface of the cornea is not considered in most studies, because it is more difficult to measure; moreover, in the case of severe corneal astigmatism, there is evidence that both surfaces have the same configuration. Noncorneal factors are errors in the curvature of the 2 surfaces of the crystalline lens, irregularity in the refractive index of the lens, and an eccentric lens position. Since the cornea is the dominant component of the eye's refracting system, a highly astigmatic cornea is likely to result in a similarly astigmatic ocular refraction (summary by Clementi et al., 1998).

Glaucoma refers loss of retinal ganglion cells in a characteristic pattern of optic neuropathy usually associated with increased intraocular pressure.

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

Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).

Nearsightedness, also known as myopia, is an eye condition that causes blurry distance vision. People who are nearsighted have more trouble seeing things that are far away (such as when driving) than things that are close up (such as when reading or using a computer). If it is not treated with corrective lenses or surgery, nearsightedness can lead to squinting, eyestrain, headaches, and significant visual impairment.\n\nNearsightedness usually begins in childhood or adolescence. It tends to worsen with age until adulthood, when it may stop getting worse (stabilize). In some people, nearsightedness improves in later adulthood.\n\nFor normal vision, light passes through the clear cornea at the front of the eye and is focused by the lens onto the surface of the retina, which is the lining of the back of the eye that contains light-sensing cells. People who are nearsighted typically have eyeballs that are too long from front to back. As a result, light entering the eye is focused too far forward, in front of the retina instead of on its surface. It is this change that causes distant objects to appear blurry. The longer the eyeball is, the farther forward light rays will be focused and the more severely nearsighted a person will be.\n\nNearsightedness is measured by how powerful a lens must be to correct it. The standard unit of lens power is called a diopter. Negative (minus) powered lenses are used to correct nearsightedness. The more severe a person's nearsightedness, the larger the number of diopters required for correction. In an individual with nearsightedness, one eye may be more nearsighted than the other.\n\nEye doctors often refer to nearsightedness less than -5 or -6 diopters as "common myopia." Nearsightedness of -6 diopters or more is commonly called "high myopia." This distinction is important because high myopia increases a person's risk of developing other eye problems that can lead to permanent vision loss or blindness. These problems include tearing and detachment of the retina, clouding of the lens (cataract), and an eye disease called glaucoma that is usually related to increased pressure within the eye. The risk of these other eye problems increases with the severity of the nearsightedness. The term "pathological myopia" is used to describe cases in which high myopia leads to tissue damage within the eye.

Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.

Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.

Primary or spontaneous detachment of the retina occurs due to underlying ocular disease and often involves the vitreous as well as the retina. The precipitating event is formation of a retinal tear or hole, which permits fluid to accumulate under the sensory layers of the retina and creates an intraretinal cleavage that destroys the neurosensory process of visual reception. Vitreoretinal degeneration and tear formation are painless phenomena, and in most cases, significant vitreoretinal pathology is found only after detachment of the retina starts to cause loss of vision or visual field. Without surgical intervention, retinal detachment will almost inevitably lead to total blindness (summary by McNiel and McPherson, 1971).

A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.

A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.

A severe form of myopia with greater than -6.00 diopters.

Underdevelopment of the optic nerve.

Nystagmus dating from or present at birth.

Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.

Decreased strength of the superior oblique muscle.