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).

The presence of multiple cysts in both kidneys.

Hypertrophy of the clitoris.

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.

Cysts of microscopic size confined to the cortex of the kidney.

A fluid filled sac in the kidney.

Clubfoot is a congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities (Cardy et al., 2007). Clubfoot may occur in isolation or as part of a syndrome (e.g., diastrophic dysplasia, 222600). Clubfoot has been reported with deficiency of long bones and mirror-image polydactyly (Gurnett et al., 2008; Klopocki et al., 2012).

Abnormal positioning in which the elbows are turned out.

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

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 insufficiency of the aortic valve, leading to regurgitation (backward flow) of blood from the aorta into the left ventricle.

An extra or unusual sound heard during a heartbeat caused vibrations resulting from the flow of blood through the heart.

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.

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.

Failure of the tricuspid valve to close sufficiently upon contraction of the right ventricle, causing blood to regurgitate (flow backward) into the right atrium.

An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.

Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age.

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.

Abnormally increased size of the liver.

Simultaneous enlargement of the liver and spleen.

Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream.

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

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.

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

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 decreased magnitude of the sensory perception of sound.

An abnormality of the helix. The helix is the outer rim of the ear that extends from the insertion of the ear on the scalp (root) to the termination of the cartilage at the earlobe.

A slow, continuous, involuntary writhing movement that prevents maintenance of a stable posture. Athetosis involves continuous smooth movements that appear random and are not composed of recognizable sub-movements or movement fragments. In contrast to chorea, in athetosis, the same regions of the body are repeatedly involved. Athetosis may worsen with attempts at movement of posture, but athetosis can also occur at rest.

A state of fatigue, either physical or mental slowness and sluggishness, with difficulties in initiating or performing simple tasks. Distinguished from apathy which implies indifference and a lack of desire or interest in the task. A person with lethargy may have the desire, but not the energy to engage in personal or socially relevant tasks.

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.

The corpus callosum is the largest fiber tract in the central nervous system and the major interhemispheric fiber bundle in the brain. Formation of the corpus callosum begins as early as 6 weeks' gestation, with the first fibers crossing the midline at 11 to 12 weeks' gestation, and completion of the basic shape by age 18 to 20 weeks (Schell-Apacik et al., 2008). Agenesis of the corpus callosum (ACC) is one of the most frequent malformations in brain with a reported incidence ranging between 0.5 and 70 in 10,000 births. ACC is a clinically and genetically heterogeneous condition, which can be observed either as an isolated condition or as a manifestation in the context of a congenital syndrome (see MOLECULAR GENETICS and Dobyns, 1996). Also see mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; 157600). Schell-Apacik et al. (2008) noted that there is confusion in the literature regarding radiologic terminology concerning partial absence of the corpus callosum, where various designations have been used, including hypogenesis, hypoplasia, partial agenesis, or dysgenesis.

Absence of neurologic reflexes such as the knee-jerk reaction.

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.

Polymicrogyria is a congenital malformation of the cerebral cortex characterized by abnormal cortical layering (lamination) and an excessive number of small gyri (folds).

Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.

Pachygyria is a malformation of cortical development with abnormally wide gyri with sulci 1,5-3 cm apart and abnormally thick cortex measuring more than 5 mm (radiological definition). See also neuropathological definitions for 2-, 3-, and 4-layered lissencephaly.

Colpocephaly is an anatomic finding in the brain manifested by occipital horns that are disproportionately enlarged in comparison with other parts of the lateral ventricles.

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.

Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.

Wasting (atrophy) of the vermis of cerebellum.

The absence of wakefulness and consciousness, but in contrast to a coma, there is involuntary opening of the eyes and movements such as teeth grinding, yawning, or thrashing of the extremities.

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.

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.

In newborns, the two frontal bones, two parietal bones, and one occipital bone are joined by fibrous sutures, which form a small posterior fontanelle, and a larger, diamond-shaped anterior fontanelle. These regions allow for the skull to pass the birth canal and for later growth. The fontanelles gradually ossify, whereby the posterior fontanelle usually closes by eight weeks and the anterior fontanelle by the 9th to 16th month of age. Large fontanelles are diagnosed if the fontanelles are larger than age-dependent norms.

The distal interphalangeal joint and/or the proximal interphalangeal joint of the fingers or toes cannot be extended to 180 degrees by either active or passive extension.

The anterior fontanelle generally ossifies by around the 18th month of life. A persistent open anterior fontanelle is diagnosed if closure is delayed beyond this age.

The presence of abnormal punctate (speckled, dot-like) calcifications in one or more epiphyses.

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

Punctate (speckled, dot-like) deposition of calcium of calcium salts in the articular cartilage (cartilage located in joints).

Abnormal increased size of the spleen.

The concentration of aspartate aminotransferase (AST) in the blood circulation is above the upper limit of normal.

An abnormally high concentration in the circulation of alanine aminotransferase (ALT).

Abnormally high level of conjugated bilirubin in the blood.

Abnormally increased serum levels of alkaline phosphatase activity.

An abnormal elevation of phytanic acid.

Increased level of the enzyme gamma-glutamyltransferase (GGT). GGT is mainly present in kidney, liver, and pancreatic cells, but small amounts are present in other tissues.

An elevated level of the enzyme lactate dehydrogenase in the blood circulation.

Increased concentration of very long-chain fatty acids in the blood circulation. Very long-chain fatty acids are fatty acids (FAs) with a chain-length of 22 or more carbons.

Edema in the region of the eyelids.

The facial appearance is more circular than usual as viewed from the front.

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).

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).

Absence of concavity or convexity of the face when viewed in profile.

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).

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

An intrauterine state characterized by suboptimal values in the fetal heart rate, oxygenation of fetal blood, or other parameters indicative of compromise of the fetus. Signs of fetal distress include repetitive variable decelerations, fetal tachycardia or bradycardia, late decelerations, or low biophysical profile.

Underdevelopment of the nipple.

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).

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.

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

Rhythmic, involuntary sinusoidal oscillations of one or both eyes. The waveform of pendular nystagmus may occur in any direction.

Reduced transparency of the stroma of cornea.

The presence of whitish spots in a ring-like arrangement at the periphery of the iris.

The presence of developmental dysplasia of the optic nerve.

An inherited retinal disease subtype in which the rod photoreceptors appear to be more severely affected than the cone photoreceptors. Typical presentation is with nyctalopia (due to rod dysfunction) followed by loss of mid-peripheral field of vision, which gradually extends and leaves many patients with a small central island of vision due to the preservation of macular cones.

An abnormality of the retina characterized by pigment deposition. It is typically associated with migration and proliferation of macrophages or retinal pigment epithelial cells into the retina; melanin from these cells causes the pigmentary changes. Pigmentary retinopathy is a common final pathway of many retinal conditions and is often associated with visual loss.