Rapid-Onset Obesity with Hypoventilation, Hypothalamic, Autonomic Dysregulation, and Neuroendocrine Tumors (ROHHADNET) Syndrome: A Systematic Review

Jiwon M. Lee, Jaewon Shin, Sol Kim, Heon Yung Gee, Joon Suk Lee, Do Hyeon Cha, John Hoon Rim, Se Jin Park, Ji Hong Kim, Ahmet Uçar, Andreas Kronbichler, Keum Hwa Lee, Jae Il Shin

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background and Aim. ROHHADNET (rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation, neuroendocrine tumor) syndrome is a rare disease with grave outcome. Although early recognition is essential, prompt diagnosis may be challenging due to its extreme rarity. This study aimed to systematically review its clinical manifestation and to identify genetic causes. Materials and Methods. We firstly conducted a systematic review on ROHHAD/NET. Electronic databases were searched using related terms. We secondly performed whole exome sequencing (WES) and examined copy number variation (CNV) in two patients to identify genetic causes. Results. In total, 46 eligible studies including 158 patients were included. There were 36 case reports available for individual patient data (IPD; 48 patients, 23 ROHHAD, and 25 ROHHADNET) and 10 case series available for aggregate patient data (APD; 110 patients, 71 ROHHAD, and 39 ROHHADNET). The median age at onset calculated from IPD was 4 years. Gender information was available in 100 patients (40 from IPD and 60 from APD) in which 65 females and 35 males were showing female preponderance. Earliest manifestation was rapid obesity, followed by hypothalamic symptoms. Most common types of neuroendocrine tumors were ganglioneuromas. Patients frequently had dysnatremia and hyperprolactinemia. Two patients were available for WES. Rare variants were identified in PIK3R3, SPTBN5, and PCF11 in one patient and SRMS, ZNF83, and KMT2B in another patient, respectively. However, there was no surviving variant shared by the two patients after filtering. Conclusions. This study systematically reviewed the phenotype of ROHHAD/NET aiming to help early recognition and reducing morbidity. The link of variants identified in the present WES requires further investigation.

Original languageEnglish
Article number1250721
JournalBioMed Research International
Volume2018
DOIs
Publication statusPublished - 2018 Jan 1

Fingerprint

Hypoventilation
pamidronate
Neuroendocrine Tumors
Tumors
Obesity
Exome
Ganglioneuroma
Hyperprolactinemia
Rare Diseases
Age of Onset

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Lee, Jiwon M. ; Shin, Jaewon ; Kim, Sol ; Gee, Heon Yung ; Lee, Joon Suk ; Cha, Do Hyeon ; Rim, John Hoon ; Park, Se Jin ; Kim, Ji Hong ; Uçar, Ahmet ; Kronbichler, Andreas ; Lee, Keum Hwa ; Shin, Jae Il. / Rapid-Onset Obesity with Hypoventilation, Hypothalamic, Autonomic Dysregulation, and Neuroendocrine Tumors (ROHHADNET) Syndrome : A Systematic Review. In: BioMed Research International. 2018 ; Vol. 2018.
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abstract = "Background and Aim. ROHHADNET (rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation, neuroendocrine tumor) syndrome is a rare disease with grave outcome. Although early recognition is essential, prompt diagnosis may be challenging due to its extreme rarity. This study aimed to systematically review its clinical manifestation and to identify genetic causes. Materials and Methods. We firstly conducted a systematic review on ROHHAD/NET. Electronic databases were searched using related terms. We secondly performed whole exome sequencing (WES) and examined copy number variation (CNV) in two patients to identify genetic causes. Results. In total, 46 eligible studies including 158 patients were included. There were 36 case reports available for individual patient data (IPD; 48 patients, 23 ROHHAD, and 25 ROHHADNET) and 10 case series available for aggregate patient data (APD; 110 patients, 71 ROHHAD, and 39 ROHHADNET). The median age at onset calculated from IPD was 4 years. Gender information was available in 100 patients (40 from IPD and 60 from APD) in which 65 females and 35 males were showing female preponderance. Earliest manifestation was rapid obesity, followed by hypothalamic symptoms. Most common types of neuroendocrine tumors were ganglioneuromas. Patients frequently had dysnatremia and hyperprolactinemia. Two patients were available for WES. Rare variants were identified in PIK3R3, SPTBN5, and PCF11 in one patient and SRMS, ZNF83, and KMT2B in another patient, respectively. However, there was no surviving variant shared by the two patients after filtering. Conclusions. This study systematically reviewed the phenotype of ROHHAD/NET aiming to help early recognition and reducing morbidity. The link of variants identified in the present WES requires further investigation.",
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Rapid-Onset Obesity with Hypoventilation, Hypothalamic, Autonomic Dysregulation, and Neuroendocrine Tumors (ROHHADNET) Syndrome : A Systematic Review. / Lee, Jiwon M.; Shin, Jaewon; Kim, Sol; Gee, Heon Yung; Lee, Joon Suk; Cha, Do Hyeon; Rim, John Hoon; Park, Se Jin; Kim, Ji Hong; Uçar, Ahmet; Kronbichler, Andreas; Lee, Keum Hwa; Shin, Jae Il.

In: BioMed Research International, Vol. 2018, 1250721, 01.01.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Rapid-Onset Obesity with Hypoventilation, Hypothalamic, Autonomic Dysregulation, and Neuroendocrine Tumors (ROHHADNET) Syndrome

T2 - A Systematic Review

AU - Lee, Jiwon M.

AU - Shin, Jaewon

AU - Kim, Sol

AU - Gee, Heon Yung

AU - Lee, Joon Suk

AU - Cha, Do Hyeon

AU - Rim, John Hoon

AU - Park, Se Jin

AU - Kim, Ji Hong

AU - Uçar, Ahmet

AU - Kronbichler, Andreas

AU - Lee, Keum Hwa

AU - Shin, Jae Il

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background and Aim. ROHHADNET (rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation, neuroendocrine tumor) syndrome is a rare disease with grave outcome. Although early recognition is essential, prompt diagnosis may be challenging due to its extreme rarity. This study aimed to systematically review its clinical manifestation and to identify genetic causes. Materials and Methods. We firstly conducted a systematic review on ROHHAD/NET. Electronic databases were searched using related terms. We secondly performed whole exome sequencing (WES) and examined copy number variation (CNV) in two patients to identify genetic causes. Results. In total, 46 eligible studies including 158 patients were included. There were 36 case reports available for individual patient data (IPD; 48 patients, 23 ROHHAD, and 25 ROHHADNET) and 10 case series available for aggregate patient data (APD; 110 patients, 71 ROHHAD, and 39 ROHHADNET). The median age at onset calculated from IPD was 4 years. Gender information was available in 100 patients (40 from IPD and 60 from APD) in which 65 females and 35 males were showing female preponderance. Earliest manifestation was rapid obesity, followed by hypothalamic symptoms. Most common types of neuroendocrine tumors were ganglioneuromas. Patients frequently had dysnatremia and hyperprolactinemia. Two patients were available for WES. Rare variants were identified in PIK3R3, SPTBN5, and PCF11 in one patient and SRMS, ZNF83, and KMT2B in another patient, respectively. However, there was no surviving variant shared by the two patients after filtering. Conclusions. This study systematically reviewed the phenotype of ROHHAD/NET aiming to help early recognition and reducing morbidity. The link of variants identified in the present WES requires further investigation.

AB - Background and Aim. ROHHADNET (rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation, neuroendocrine tumor) syndrome is a rare disease with grave outcome. Although early recognition is essential, prompt diagnosis may be challenging due to its extreme rarity. This study aimed to systematically review its clinical manifestation and to identify genetic causes. Materials and Methods. We firstly conducted a systematic review on ROHHAD/NET. Electronic databases were searched using related terms. We secondly performed whole exome sequencing (WES) and examined copy number variation (CNV) in two patients to identify genetic causes. Results. In total, 46 eligible studies including 158 patients were included. There were 36 case reports available for individual patient data (IPD; 48 patients, 23 ROHHAD, and 25 ROHHADNET) and 10 case series available for aggregate patient data (APD; 110 patients, 71 ROHHAD, and 39 ROHHADNET). The median age at onset calculated from IPD was 4 years. Gender information was available in 100 patients (40 from IPD and 60 from APD) in which 65 females and 35 males were showing female preponderance. Earliest manifestation was rapid obesity, followed by hypothalamic symptoms. Most common types of neuroendocrine tumors were ganglioneuromas. Patients frequently had dysnatremia and hyperprolactinemia. Two patients were available for WES. Rare variants were identified in PIK3R3, SPTBN5, and PCF11 in one patient and SRMS, ZNF83, and KMT2B in another patient, respectively. However, there was no surviving variant shared by the two patients after filtering. Conclusions. This study systematically reviewed the phenotype of ROHHAD/NET aiming to help early recognition and reducing morbidity. The link of variants identified in the present WES requires further investigation.

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