MedGen

Congenital central hypoventilation syndrome (CCHS) represents the extreme manifestation of autonomic nervous system dysregulation (ANSD) with the hallmark of disordered respiratory control. The age of initial recognition of CCHS ranges from neonatal onset (i.e., in the first 30 days of life) to (less commonly) later onset (from 1 month to adulthood). Neonatal-onset CCHS is characterized by apparent hypoventilation with monotonous respiratory rates and shallow breathing either during sleep only or while awake as well as asleep; ANSD including decreased heart rate beat-to-beat variability and sinus pauses; altered temperature regulation; and altered pupillary response to light. Some children have altered development of neural crest-derived structures (i.e., Hirschsprung disease, altered esophageal motility/dysphagia, and severe constipation even in the absence of Hirschsprung disease) and/or tumors of neural crest origin (neuroblastoma, ganglioneuroma, and ganglioneuroblastoma). Neurocognitive delay is variable, and possibly influenced by cyanotic breath holding, prolonged sinus pauses, need for 24-hour/day artificial ventilation, and seizures. Later-onset CCHS is characterized by alveolar hypoventilation during sleep and attenuated manifestations of ANSD. [from GeneReviews]

Stuve-Wiedemann syndrome is an autosomal recessive disorder characterized by bowing of the long bones and other skeletal anomalies, episodic hyperthermia, respiratory distress, and feeding difficulties usually resulting in early death (Dagoneau et al., 2004). See also 'classic' Schwartz-Jampel syndrome type 1 (SJS1; 255800), a phenotypically similar but genetically distinct disorder caused by mutation in the HSPG2 gene (142461) on chromosome 1p36. Genetic Heterogeneity of Stuve-Wiedemann Syndrome Stuve-Wiedemann syndrome-2 (STWS2; 619751) is caused by mutation in the IL6ST gene (600694) on chromosome 5q11. [from OMIM]

Joubert syndrome-35 (JBTS35) is an autosomal recessive disorder characterized by brain malformations that result in developmental delay, oculomotor apraxia, and hypotonia. Some patients have renal and retinal involvement (Alkanderi et al., 2018). For a discussion of genetic heterogeneity of Joubert syndrome, see JBTS1 (213300). [from OMIM]

Hypotonia, hypoventilation, impaired intellectual development, dysautonomia, epilepsy, and eye abnormalities (HIDEA) is an autosomal recessive neurodevelopmental syndrome characterized by global developmental delay, poor or absent speech, hypotonia, variable ocular movement and visual abnormalities, and respiratory difficulties, including hypoventilation, and sleep apnea. Patients may have significant breathing problems during respiratory infections that may lead to early death (summary by Rahikkala et al., 2019). [from OMIM]

DEEAH syndrome is an autosomal recessive multisystemic disorder with onset in early infancy. Affected individuals usually present in the perinatal period with respiratory insufficiency, apneic episodes, and generalized hypotonia. The patients have failure to thrive and severely impaired global development with poor acquisition of motor, cognitive, and language skills. Other common features include endocrine, pancreatic exocrine, and autonomic dysfunction, as well as hematologic disturbances, mainly low hemoglobin. Patients also have dysmorphic and myopathic facial features. Additional more variable features include seizures, undescended testes, and distal skeletal anomalies. Death in early childhood may occur (summary by Schneeberger et al., 2020). [from OMIM]

Childhood-onset neurodegeneration with hypotonia, respiratory insufficiency, and brain imaging abnormalities (CONRIBA) is characterized by severe global developmental delay apparent in infancy or early childhood. Affected individuals have hypotonia with impaired motor development, respiratory insufficiency, and feeding difficulties requiring intervention. Intellectual and speech development is also delayed, and most have visual defects, including cortical visual blindness, nystagmus, and esotropia. The disorder is progressive, as manifest by developmental regression consistent with neurodegeneration. Although overt seizures are not observed, some patients may have episodic hypertonia or apnea, and EEG may show nonspecific abnormalities. Brain imaging shows unique diffusion restriction signal abnormalities affecting the brainstem, cerebellum, and corticospinal tracts. Early death may occur (summary by Polovitskaya et al., 2020). [from OMIM]

An abnormality of temperature homeostasis. [from HPO]