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).

A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced.

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

Coxa valga is a deformity of the hip in which the angle between the femoral shaft and the femoral neck is increased compared to age-adjusted values (about 150 degrees in newborns gradually reducing to 120-130 degrees in adults).

Spoon-shaped, broad thumbs.

A dislocation of the head of the radius from its socket in the elbow joint.

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

The legs angle inward, such that the knees are close together and the ankles far apart.

Diminished length of one or more metacarpal bones in relation to the others of the same hand or to the contralateral metacarpal.

Ossification of carpal bones at an abnormally early age.

Abnormally wide (broad) distal phalanx of finger.

A bending or abnormal curvature of the radius.

The presence of developmental dysplasia of the femoral head.

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

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.

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 severe degree of short stature, more than -4 SD from the mean corrected for age and sex.

Abnormally low body weight.

Severe or complete weakness of both lower extremities with sparing of the upper extremities.

External mechanical compression of the spinal cord.

A pathologic fracture occurs when a bone breaks in an area that is weakened secondarily to another disease process such as tumor, infection, and certain inherited bone disorders. A pathologic fracture can occur without a degree of trauma required to cause fracture in healthy bone.

Displacement of the femur from its normal location in the hip joint.

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.

Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD).

Partial dislocation of the head of the radius.

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

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.

Synostosis (bony fusion) involving one or more bones of the carpus (scaphoid, lunate, triquetrum, trapezium, trapezoid, capitate, hamate, pisiform).

An osteochondrodysplasia that results in abnormalities of bone growth in the vertebral column, epiphysis, and metaphysis.

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

Reduced diameter of a long bone.

An abnormally short femoral neck (which is the process of bone, connecting the femoral head with the femoral shaft).

Presence of only 11 pairs of ribs.

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

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.

Underdevelopment of the body of ilium.

Abnormal widening of the metaphyseal regions of long bones.

The presence of a splayed (i.e.,flared) metaphyseal segment of one or more long bones.

The presence of wide, concave anterior rib ends.

One or more abnormally short long bone.

Developmental delay of ossification of the proximal epiphysis of the femur.

When viewed in lateral radiographs, vertebral bodies have a roughly rectangular configuration. This term applies if the vertebral body appears rounded or oval.

Anterior tongue-like protrusions of the vertebral bodies.

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

Wide, concave rib end.

Widening of the ilium ala, that is of the wing of the ilium, combined with external rotation, leading to a flared appearance of the iliac wing.

Increased size of the ilium ala.

A morphological anomaly of the rib cage.

The capability that a large joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes. Large joints include shoulders, elbows, hips, knees, and ankles.

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).

Diminished length of the neck.

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

A face with a rounded and slightly elongated outline.

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

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

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

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.

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).

Increased width of the upper lip.

Wrinkled, redundant, inelastic and sagging skin.

A condition in which the skin can be stretched beyond normal, and then returns to its initial position.

Skin that splits easily with minimal injury.

Decreased length of nail.

A skin texture that is unusually soft (and may feel silky), and has a malleable consistency resembling that of dough.

Dislocation or malposition of the crystalline lens of the eye. A partial displacement (or dislocation) of the lens is described as a subluxation of the lens, while a complete displacement is termed luxation of the lens. A complete displacement occurs if the lens is completely outside the patellar fossa of the lens, either in the anterior chamber, in the vitreous, or directly on the retina. If the lens is partially displaced but still contained within the lens space, then it is termed subluxation.

An eye that is protruding anterior to the plane of the face to a greater extent than is typical.

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.

An abnormal bluish coloration of the sclera.