CCHS Related Conditions

Congenital Myopathy is a term for any muscle disorder present at birth. By this definition the congenital myopathies could include hundreds of distinct neuromuscular syndromes and disorders. In general, congenital myopathies cause loss of muscle tone and muscle weakness in infancy and delayed motor milestones, such as walking, later in childhood. Three distinct disorders are definitively classified as congenital myopathies: central core disease, nemaline rod myopathy, and centronuclear (myotubular) yopathy.

Congenital Myasthenia usually occurs in infants but may become evident in adulthood. Associated features may vary in severity from case to case. Such abnormalities may include feeding difficulties, periods with absence of spontaneous breathing (apnea), failure to grow and gain weight at the expected rate, muscle weakness and fatigue, weakness or paralysis of eye muscles (ophthalmoplegia), and/or other abnormalities.

Moebius Syndrome is a rare developmental disorder that may have a number of different causes and is characterized by facial paralysis present at birth (congenital). Facial nerve development is absent or diminished causing abnormalities of the facial muscles and jaw. Additional symptoms may include numerous abnormalities of the mouth and face (orofacial region) and potentially malformations of limbs. Intellectual disability occurs in approximately 10 percent of patients. (For more information on this disorder, choose “Moebius” as your search term in the Rare Disease Database.)

When CCHS occurs in adults it may be confused with other more common respiratory diseases such as obstructive sleep apnea unresponsive to traditional management. Notably individuals with CCHS, regardless of age at presentation/diagnosis, will not have shortness of breath as they do not perceive low oxygen or elevated carbon dioxide. After the airway obstruction has been treated, the hypoventilation becomes more apparent. Among adults in whom a diagnosis of CCHS is considered, a careful family tree asking about offspring with CCHS should be obtained.

Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is a related but separate disorder. Children with ROHHAD typically present between the ages of 1.5 and 7 years of age with a rapid weight gain of 20 or more pounds over a 6 month period. They are then noted to have symptoms of hypothalamic dysfunction such as water imbalance, growth insufficiency, hypothyroidism, cortisol abnormalities, and more. A subset of the cases of ROHHAD will experience a respiratory arrest early in their course but subsequent to another illness. Many of the children with ROHHAD will have obstructive sleep apnea and once this is treated, the children will be noted to have hypoventilation, even among those who did not endure a cardiorespiratory arrest. Children with ROHHAD do not have CCHS-related mutations in the PHOX2B gene. The genetic basis for ROHHAD is not yet known.
 
For more information on this disorder, visit the ROHHAD page at rarediseases.org.

Central Hypoventilation and apnea are a diverse collection of medical abnormalities associated with faults in breathing. CCHS is known to be caused by a PHOX2B mutation. Not all central hypoventilation and apnea causes are known. Some genes known to be related to Central Hypoventilation and Apnea are:

  • CHAT: Myasthenic syndrome, congenital
  • CHRNA1: Myasthenic syndrome, congenital
  • CHRNB1: Myasthenic syndrome
  • CHRND: Myasthenic syndrome
  • CHRNE: Myasthenic syndrome
  • COLQ: Myasthenic syndrome, congenital
  • EDN3: Hirschsprung disease, Central hypoventilation syndrome, congenital, Waardenburg syndrome
  • GLRA1: Hyperekplexia AD/AR
  • MECP2: Angelman-like syndrome, Autism, Rett syndrome, Encephalopathy, Mental retardation
  • PHOX2B: Central hypoventilation syndrome, congenital, Neuroblastoma, susceptiblity to, Neuroblastoma with Hirschsprung disease
  • RAPSN: Myasthenic syndrome, congenital
  • RET: Hirschsprung disease, Central hypoventilation syndrome, congenital, Pheochromocytoma, Medullary thyroid carcinoma, Multiple endocrine neoplasia
  • SCN4A: Hyperkalemic periodic paralysis, Myotonia, potassium-aggravated, Paramyotonia congenita, Myasthenic syndrome, congenital, Normokalemic potassium-sensitive periodic paralysis
  • SLC6A5: Hyperekplexia
  • ZEB2: Mowat-Wilson syndrome