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).

Hypoplasia of the kidney.

The distention of the ureter with urine.

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.

Absence or underdevelopment of the kidney.

Webbing or fusion of the fingers or toes, 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 or toes in a proximo-distal axis are referred to as "symphalangism".

Bending or curvature of a finger toward the radial side (i.e., towards the thumb). The deviation is at the metacarpal-phalangeal joint, and this finding is distinct from clinodactyly.

An abnormality of the dermatoglyphs, i.e., an abnormality of the patterns of ridges of the skin of palm of hand.

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

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).

A deficiency or slowing down of growth pre- and postnatally.

Congenital absence of the anus, i.e., the opening at the bottom end of the intestinal tract.

The disorder described by Hirschsprung (1888) and known as Hirschsprung disease or aganglionic megacolon is characterized by congenital absence of intrinsic ganglion cells in the myenteric (Auerbach) and submucosal (Meissner) plexuses of the gastrointestinal tract. Patients are diagnosed with the short-segment form (S-HSCR, approximately 80% of cases) when the aganglionic segment does not extend beyond the upper sigmoid, and with the long-segment form (L-HSCR) when aganglionosis extends proximal to the sigmoid (Amiel et al., 2008). Total colonic aganglionosis and total intestinal HSCR also occur. Genetic Heterogeneity of Hirschsprung Disease Several additional loci for isolated Hirschsprung disease have been mapped. HSCR2 (600155) is associated with variation in the EDNRB gene (131244) on 13q22; HSCR3 (613711) is associated with variation in the GDNF gene (600837) on 5p13; HSCR4 (613712) is associated with variation in the EDN3 gene (131242) on 20q13; HSCR5 (600156) maps to 9q31; HSCR6 (606874) maps to 3p21; HSCR7 (606875) maps to 19q12; HSCR8 (608462) maps to 16q23; and HSCR9 (611644) maps to 4q31-q32. HSCR also occurs as a feature of several syndromes including the Waardenburg-Shah syndrome (277580), Mowat-Wilson syndrome (235730), Goldberg-Shprintzen syndrome (609460), and congenital central hypoventilation syndrome (CCHS; 209880). Whereas mendelian modes of inheritance have been described for syndromic HSCR, isolated HSCR stands as a model for genetic disorders with complex patterns of inheritance. Isolated HSCR appears to be of complex nonmendelian inheritance with low sex-dependent penetrance and variable expression according to the length of the aganglionic segment, suggestive of the involvement of one or more genes with low penetrance. The development of surgical procedures decreased mortality and morbidity, which allowed the emergence of familial cases. HSCR occurs as an isolated trait in 70% of patients, is associated with chromosomal anomaly in 12% of cases, and occurs with additional congenital anomalies in 18% of cases (summary by Amiel et al., 2008).

Protrusion of the rectal mucous membrane through the anus.

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.

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.

An abnormality of the pinna, which is also referred to as the auricle or external ear.

A decreased magnitude of the sensory perception of sound.

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.

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).

Spasticity (neuromuscular hypertonia) primarily in the muscles of the legs, hips, and pelvis.

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.

Deliberate harm to one's body resulting in tissue damage, without a conscious intent to die.

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 type of Developmental delay characterized by a delay in acquiring motor skills.

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.

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 an abnormal lateral curvature of the spine.

Contractures of one ore more joints of the hands meaning chronic loss of joint motion due to structural changes in non-bony tissue.

Reduced width of the chest from side to side, associated with a reduced distance from the sternal notch to the tip of the shoulder.

Reduced length of the clavicles.

An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane.

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.

An abnormal accentuation of the inward curvature of the spine in the lumbar region.

Low set, steeply sloping shoulders.

Generalized muscular hypotonia (abnormally low muscle tone).

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

Head circumference below 2 standard deviations below the mean for age and gender.

A congenital abnormality in which the lung parenchyma is not fully developed. It may be associated with other congenital abnormalities.

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

A gap or groove in the upper lip. This is a congenital defect resulting from nonfusion of tissues of the lip during embryonal development.

Changes in alignment of teeth in the dental arch

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.

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).

The presence of a high and narrow palate.

Agenesis of one or more maxillary lateral incisor, comprising the maxillary lateral primary incisor and maxillary lateral secondary incisor.

Abnormal alignment, positioning, or spacing of the teeth, i.e., misaligned teeth.

The presence of a cleft (gap, opening, or groove) in the oral cavity, including cleft of the upper lip and/or cleft of the palate. Cleft of the upper lip is visible as a groove or fissure in the lip, most frequently due to a congenital failure of the maxillary and median nasal processes to fuse. Cleft palate is characterized by a grooved depression or fissure in the roof of the mouth, most often resulting from a congenital failure of the palate to fuse properly. Clefts of the lip and palate can occur individually or together. It is preferable to code each defect separately.

A soft tissue prominence of the ventral aspects of the fingertips. The term "persistent fetal fingertip pads" is often used as a synonym, but should better not be used because it implies knowledge of history of the patient which often does not exist.

Absence of the globe or eyeball.

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).

Microphthalmia is an eye abnormality that arises before birth. In this condition, one or both eyeballs are abnormally small. In some affected individuals, the eyeball may appear to be completely missing; however, even in these cases some remaining eye tissue is generally present. Such severe microphthalmia should be distinguished from another condition called anophthalmia, in which no eyeball forms at all. However, the terms anophthalmia and severe microphthalmia are often used interchangeably. Microphthalmia may or may not result in significant vision loss.\n\nPeople with microphthalmia may also have a condition called coloboma. Colobomas are missing pieces of tissue in structures that form the eye. They may appear as notches or gaps in the colored part of the eye called the iris; the retina, which is the specialized light-sensitive tissue that lines the back of the eye; the blood vessel layer under the retina called the choroid; or in the optic nerves, which carry information from the eyes to the brain. Colobomas may be present in one or both eyes and, depending on their size and location, can affect a person's vision.\n\nPeople with microphthalmia may also have other eye abnormalities, including clouding of the lens of the eye (cataract) and a narrowed opening of the eye (narrowed palpebral fissure). Additionally, affected individuals may have an abnormality called microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved.\n\nBetween one-third and one-half of affected individuals have microphthalmia as part of a syndrome that affects other organs and tissues in the body. These forms of the condition are described as syndromic. When microphthalmia occurs by itself, it is described as nonsyndromic or isolated.

A cleft of the optic nerve that extends inferiorly.

A coloboma of the iris.

Absence of a region of the retina, retinal pigment epithelium, and choroid.

A congenital abnormality of the cornea in which the cornea and the anterior segment of the eye are smaller than normal. The horizontal diameter of the cornea does not reach 10 mm even in adulthood.

Blindness is the condition of lacking visual perception defined as a profound reduction in visual perception. On the 6m visual acuity scale, blindness is defined as less than 3/60. On the 20ft visual acuity scale, blindness is defined as less than 20/400. On the decimal visual acuity scale, blindness is defined as less than 0.05. Blindness is typically characterized by a visual field of no greater than 10 degrees in radius around central fixation.

A coloboma of the ciliary body.