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

Vesicoureteral reflux (VUR) is characterized by the reflux of urine from the bladder into the ureters and sometimes into the kidneys. It is a risk factor for urinary tract infections. Primary VUR results from a developmental defect of the ureterovesical junction (UVJ). In combination with intrarenal reflux, the resulting inflammatory reaction may result in renal injury or scarring, also called reflux nephropathy (RN). Extensive renal scarring impairs renal function and may predispose patients to hypertension, proteinuria, and renal insufficiency (summary by Lu et al., 2007). Genetic Heterogeneity of Vesicoureteral Reflux A locus designated VUR1 maps to chromosome 1p13. VUR2 (610878) is caused by mutation in the ROBO2 gene (602431) on chromosome 3p12; VUR3 (613674) is caused by mutation in the SOX17 gene (610928) on chromosome 8q11; VUR4 (614317) maps to chromosome 5; VUR5 (614318) maps to chromosome 13; VUR6 (614319) maps to chromosome 18; VUR7 (615390) maps to chromosome 12; and VUR8 (615963) is caused by mutation in the TNXB gene (600985) on chromosome 6p21. A possible X-linked form has been reported (VURX; 314550).

Hypertrophy of the clitoris.

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

The presence of a bicornuate uterus.

The presence of a vaginal septum, thereby creating a vaginal duplication. The septum is longitudinal in the majority of cases.

The distention of the ureter with urine.

A developmental anomaly in which the kidneys are fused and localized on the same side of the midline. This anomaly is thought to result from disruption of the normal embryologic migration of the kidneys.

Underdevelopment of the urinary bladder.

Webbing or fusion of the 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 toes 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.

Syndactyly with fusion of toes three and four.

Bilateral clubfoot deformity.

Syndactyly with fusion of toes four and five.

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

Syndactyly with fusion of toes three to five.

Failure of the foramen ovale to seal postnatally, leaving a potential conduit between the left and right cardiac atria.

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.

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).

Stenosis of a peripheral branch of the pulmonary artery.

A cardiovascular malformation associated with narrowing of the outflow tract of the right ventricle immediately at the level of the pulmonary valve.

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.

A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).

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

The presence of a fistula between the vagina and the rectum.

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.

Anterior and inferior folding of the upper portion of the ear that obliterates triangular fossa and scapha.

The closed form of spina bifida with incomplete closure of a vertebral body with intact overlying skin.

Craniosynostosis refers to the premature closure of the cranial sutures. Primary craniosynostosis refers to the closure of one or more sutures due to abnormalities in skull development, and secondary craniosynostosis results from failure of brain growth.

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

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

Interalar distance more than two standard deviations above the mean for age, i.e., an apparently increased width of the nasal base and alae.

Interalar distance more than 2 SD below the mean for age, or alternatively, an apparently decreased width of the nasal base and alae.

Increase in width of the nasal tip.

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 above the mean (objective); or apparently increased distance between the two sides of the forehead.

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).

Duane syndrome is a strabismus condition clinically characterized by congenital non-progressive limited horizontal eye movement accompanied by globe retraction which results in narrowing of the palpebral fissure. The lateral movement anomaly results from failure of the abducens nucleus and nerve (cranial nerve VI) to fully innervate the lateral rectus muscle; globe retraction occurs as a result of abnormal innervation of the lateral rectus muscle by the oculomotor nerve (cranial nerve III). At birth, affected infants have restricted ability to move the affected eye(s) outward (abduction) and/or inward (adduction), though the limitations may not be recognized in early infancy. In addition, the globe retracts into the orbit with attempted adduction, accompanied by narrowing of the palpebral fissure. Many individuals with Duane syndrome have strabismus in primary gaze but can use a compensatory head turn to align the eyes, and thus can preserve binocular vision and avoid diplopia. Individuals with Duane syndrome who lack binocular vision are at risk for amblyopia. The majority of affected individuals with Duane syndrome have isolated Duane syndrome (i.e., they do not have other detected congenital anomalies). Other individuals with Duane syndrome fall into well-defined syndromic diagnoses. However, many individuals with Duane syndrome have non-ocular findings that do not fit a known syndrome; these individuals are included as part of the discussion of nonsyndromic Duane syndrome.

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