ALK-related neuroblastic tumor susceptibility is characterized by increased risk for neuroblastic tumors including neuroblastoma, ganglioneuroblastoma, and ganglioneuroma. Neuroblastoma is a more malignant tumor and ganglioneuroma a more benign tumor. Depending on the histologic findings, ganglioneuroblastoma can behave in a more aggressive fashion, like neuroblastoma, or in a benign fashion, like ganglioneuroma. Preliminary data from the ten reported families with ALK-related neuroblastic tumor susceptibility suggest an overall penetrance of approximately 57% with the risk for neuroblastic tumor development highest in infancy and decreasing by late childhood.

Ganglioneuroblastoma is a rare type of primitive neuroectodermal tumor (PNET; see this term), affecting almost exclusively infants and young children under the age of 10, usually occurring in the posterior mediastinum, adrenal medulla and extra-adrenal retroperitoneum (but sometimes in the neck and pelvis), with metastasis most often presenting in the bones, and characterized clinically by pain, stridor, shortness of breath, peripheral neurological signs, superior vena cava syndrome and congenital Horner syndrome (see this term), depending on the location of the tumor.

Reduced variation of beat-to-beat intervals of the heart that occurs in conjunction with the respiratory cycle.

Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.

Constipation for longer than three months with fewer than 3 bowel movements per week, straining, lumpy or hard stools, and a sensation of anorectal obstruction or incomplete defecation.

Reduced or inadequate esophageal peristalsis, with resultant slow passage of contents through the esophagus.

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.

A type of abnormal location of the ears in which the position of the ears is characterized by posterior rotation (the superior part of the ears is rotated towards the back of the head, and the inferior part of the ears towards the front).

A functional abnormality of the autonomic nervous system.

A benign neoplasm that usually arises from the sympathetic trunk in the mediastinum, representing a tumor of the sympathetic nerve fibers arising from neural crest cells.

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).

Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event.

Abnormally elevated blood carbon dioxide (CO2) level.

An abnormally low level of blood oxygen.

An abnormal reduction in alveolar ventilation occuring during sleep. This is characterized by a rise in arterial carbon dioxide.

A reduction in the amount of air transported into the pulmonary alveoli by breathing, leading to hypercapnia (increase in the partial pressure of carbon dioxide).

An abnormality of temperature homeostasis.

The palpebral fissure inclination is more than two standard deviations below the mean.

Abnormal excessive perspiration (sweating) despite the lack of appropriate stimuli like hot and humid weather.