Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.

Abnormal protrusion of the scapula away from the surface of the back.

A soft tissue continuity in the A/P axis between two fingers that extends distally to at least the level of the proximal interphalangeal joints, or a soft tissue continuity in the A/P axis between two fingers that lies significantly distal to the flexion crease that overlies the metacarpophalangeal joint of the adjacent fingers.

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

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

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).

Spasticity and weakness of the leg and hip muscles.

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.

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

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

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

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

A fixed reduction in the vertical distance between the upper and lower eyelids with short palpebral fissures.

Abnormal prominence of the chin related to increased length of the mandible.

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

Increased breadth of the nasal bridge (and with it, the nasal root).

Anterior positioning of the nasal root in comparison to the usual positioning for age.

Development of gray hair at a younger than normal age.

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

Meeting of the medial eyebrows in the midline.

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.

A markedly blue coloration of the iris.