Congenital central hypoventilation syndrome (CCHS) represents the extreme manifestation of autonomic nervous system dysregulation (ANSD), with a hallmark of disordered respiratory control. It is caused by mutations in the Paired-like homeobox gene, PHOX2B. CCHS is characterized by adequate ventilation when awake but apparent hypoventilation with shallow breathing asleep. More severely affected individuals hypoventilate awake and asleep. Most patients present in the neonatal period, but a small subset present over one month of age and into adulthood. Patients with CCHS rely on artificial ventilation as life support.
Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is comprised of a unique constellation of symptoms with onset between 1.5-7 years of age in otherwise healthy children. The herald is the rapid gain of 20-30 pounds over 3-12 months, typically followed by other features of hypothalamic dysfunction, then hypoventilation, followed by autonomic dysregulation. The symptoms typically "unfold" over time, and with optimized care, a subset of patients will have an improvement in awake hypoventilation. Patients with ROHHAD require artificial ventilation as life-support during sleep, and when most severe awake and asleep.
Prader-Willi Syndrome
Prader-Willi syndrome (PWS) is a multifaceted neurodevelopmental disorder characterized by hypotonia, hyperphagia, and developmental delay. PWS is caused by a loss of expression for one or more paternally expressed genes in the 15q11.2-q13.1 region (the PWS/AS critical region). Significant hallmarks of PWS include poor postnatal feeding in infancy followed by rapid obesity later in childhood caused by hyperphagia. Short stature is a common feature, requiring growth hormone treatment. Sleep disturbances are also common. Other significant features can include neuropsychiatric phenotypes including intellectual disability, autism and cycloid psychosis. Many individual aspects of the syndrome are treatable, but behavior management and restricted calorie intake are critical.
Common and disparate themes among these disorders.
Though a genetic basis has been identified for CCHS and Prader-Willi Syndrome, the basis for ROHHAD remains elusive despite extensive inquiry. The overlapping phenotypes include abnormalities in the control of breathing and autonomic regulation among all 3 syndromes; obesity among ROHHAD and PWS; and varying severity of hypothalamic abnormalities among the 3 syndromes, though rarely in CCHS.
The goals of the Research Topic are to:
• Raise awareness of hypoventilation and autonomic disorders and how to identify them with the aim to decrease the risk of morbidity and mortality.
• Differentiate syndromic types of obesity.
• Educate clinicians and researchers of the critical need to identify patients as young as possible, perform appropriate physiologic, autonomic, genetic and endocrine testing to confirm diagnoses, and implement life-saving management acutely and longitudinally.
• Identify molecular or behavioral commonalities among these disorders.
• Expand the spectrum of cases that may share more features across these syndromes.
We are seeking Clinical and Basic Science studies that will address the basis of these 3 conditions (CCHS, ROHHAD, PWS), address how to distinguish among the overlapping phenotypes, and how to provide optimal care and follow-up. Studies involving patient-derived cells lines or tissues are encouraged in addition to clinical series directly comparing these disorders.
Congenital central hypoventilation syndrome (CCHS) represents the extreme manifestation of autonomic nervous system dysregulation (ANSD), with a hallmark of disordered respiratory control. It is caused by mutations in the Paired-like homeobox gene, PHOX2B. CCHS is characterized by adequate ventilation when awake but apparent hypoventilation with shallow breathing asleep. More severely affected individuals hypoventilate awake and asleep. Most patients present in the neonatal period, but a small subset present over one month of age and into adulthood. Patients with CCHS rely on artificial ventilation as life support.
Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is comprised of a unique constellation of symptoms with onset between 1.5-7 years of age in otherwise healthy children. The herald is the rapid gain of 20-30 pounds over 3-12 months, typically followed by other features of hypothalamic dysfunction, then hypoventilation, followed by autonomic dysregulation. The symptoms typically "unfold" over time, and with optimized care, a subset of patients will have an improvement in awake hypoventilation. Patients with ROHHAD require artificial ventilation as life-support during sleep, and when most severe awake and asleep.
Prader-Willi Syndrome
Prader-Willi syndrome (PWS) is a multifaceted neurodevelopmental disorder characterized by hypotonia, hyperphagia, and developmental delay. PWS is caused by a loss of expression for one or more paternally expressed genes in the 15q11.2-q13.1 region (the PWS/AS critical region). Significant hallmarks of PWS include poor postnatal feeding in infancy followed by rapid obesity later in childhood caused by hyperphagia. Short stature is a common feature, requiring growth hormone treatment. Sleep disturbances are also common. Other significant features can include neuropsychiatric phenotypes including intellectual disability, autism and cycloid psychosis. Many individual aspects of the syndrome are treatable, but behavior management and restricted calorie intake are critical.
Common and disparate themes among these disorders.
Though a genetic basis has been identified for CCHS and Prader-Willi Syndrome, the basis for ROHHAD remains elusive despite extensive inquiry. The overlapping phenotypes include abnormalities in the control of breathing and autonomic regulation among all 3 syndromes; obesity among ROHHAD and PWS; and varying severity of hypothalamic abnormalities among the 3 syndromes, though rarely in CCHS.
The goals of the Research Topic are to:
• Raise awareness of hypoventilation and autonomic disorders and how to identify them with the aim to decrease the risk of morbidity and mortality.
• Differentiate syndromic types of obesity.
• Educate clinicians and researchers of the critical need to identify patients as young as possible, perform appropriate physiologic, autonomic, genetic and endocrine testing to confirm diagnoses, and implement life-saving management acutely and longitudinally.
• Identify molecular or behavioral commonalities among these disorders.
• Expand the spectrum of cases that may share more features across these syndromes.
We are seeking Clinical and Basic Science studies that will address the basis of these 3 conditions (CCHS, ROHHAD, PWS), address how to distinguish among the overlapping phenotypes, and how to provide optimal care and follow-up. Studies involving patient-derived cells lines or tissues are encouraged in addition to clinical series directly comparing these disorders.