An organ or organ-system abnormality that consists of uncontrolled autonomous cell-proliferation which can occur in any part of the body as a benign or malignant neoplasm (tumor).

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).

An abnormality of the ear.

Piebaldism is a rare autosomal dominant trait characterized by the congenital absence of melanocytes in affected areas of the skin and hair. A white forelock of hair, often triangular in shape, may be the only manifestation, or both the hair and the underlying forehead may be involved. The eyebrows and eyelashes may be affected. Irregularly shaped white patches may be observed on the face, trunk, and extremities, usually in a symmetrical distribution. Typically, islands of hyperpigmentation are present within and at the border of depigmented areas (summary by Thomas et al., 2004).

A triangular depigmented region of white hairs located in the anterior midline of the scalp.

Lack of skin pigmentation (coloring) of the anterior chest.

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.

Heterochromia iridis is a difference in the color of the iris in the two eyes.

Piebaldism is a rare autosomal dominant trait characterized by the congenital absence of melanocytes in affected areas of the skin and hair. A white forelock of hair, often triangular in shape, may be the only manifestation, or both the hair and the underlying forehead may be involved. The eyebrows and eyelashes may be affected. Irregularly shaped white patches may be observed on the face, trunk, and extremities, usually in a symmetrical distribution. Typically, islands of hyperpigmentation are present within and at the border of depigmented areas (summary by Thomas et al., 2004).

Syndrome with characteristics of congenital nerve deafness and piebaldness without ocular albinism. Transmission is X-linked with affected males presenting with profound sensorineural deafness and severe pigmentary abnormalities of the skin and carrier females presenting with variable hearing impairment without any pigmentary changes. The causative gene has been mapped to Xq26.3-q27.1.