Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD): a collaborative review of the current understanding.

Purpose: To provide an overview of the discovery, presentation, and management of Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD). To discuss a search for causative etiology spanning multiple disciplines and continents.

Methods: The literature (1965-2022) on the diagnosis, management, pathophysiology, and potential etiology of ROHHAD was methodically reviewed.

Kaposiform Lymphangiomatosis: Pathologic Aspects in 43 Patients.

Kaposiform lymphangiomatosis is an uncommon generalized lymphatic anomaly with distinctive clinical, radiologic, histopathologic, and molecular findings. Herein, we document the pathology in 43 patients evaluated by the Boston Children's Hospital Vascular Anomalies Center from 1999 to 2020. The most frequent presentations were respiratory difficulty, hemostatic abnormalities, and a soft tissue mass.

Evaluation of ɛ2/ɛ3/ɛ4 Alleles in a Cohort of Individuals Affected by Developmental Topographical Disorientation.

The three common alleles of the gene, ɛ2/ɛ3/ɛ4, have been linked to human spatial orientation. We investigated the genetic role of in developmental topographical disorientation (DTD), a lifelong condition that results in topographical disorientation. We genotyped the ɛ2/ɛ3/ɛ4 alleles in a cohort of 20 unrelated DTD probands, and found allele frequencies not statistically different from the those seen in the population as a whole.

A somatic activating NRAS variant associated with kaposiform lymphangiomatosis.

Purpose: Kaposiform lymphangiomatosis (KLA) is a rare, frequently aggressive, systemic disorder of the lymphatic vasculature, occurring primarily in children. Even with multimodal treatments, KLA has a poor prognosis and high mortality rate secondary to coagulopathy, effusions, and systemic involvement. We hypothesized that, as has recently been found for other vascular anomalies, KLA may be caused by somatic mosaic variants affecting vascular development.

ROHHAD and Prader-Willi syndrome (PWS): clinical and genetic comparison.

Background: Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a very rare and potentially fatal pediatric disorder, the cause of which is presently unknown. ROHHAD is often compared to Prader-Willi syndrome (PWS) because both share childhood obesity as one of their most prominent and recognizable signs, and because other symptoms such as hypoventilation and autonomic dysfunction are seen in both. These phenotypic similarities suggest they might be etiologically related conditions.

Familial aggregation in developmental topographical disorientation (DTD).

A variety of brain lesions may affect the ability to orient, resulting in what is termed "acquired topographical disorientation". In some individuals, however, topographical disorientation is present from childhood, with no apparent brain abnormalities and otherwise intact general cognitive abilities, a condition referred to as "developmental topographical disorientation" (DTD). Individuals affected by DTD often report relatives experiencing the same lifelong orientation difficulties.

Absence of mutations in HCRT, HCRTR1 and HCRTR2 in patients with ROHHAD.

Background And Objectives: Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare pediatric disease of unknown cause. Here, in response to a recent case report describing a ROHHAD patient who suffered from secondary narcolepsy confirmed by an absence of hypocretin-1 in the cerebrospinal fluid, we consider whether the ROHHAD phenotype is owing to one or more mutations in genes specific to hypocretin protein signalling.

Methods: DNA samples from 16 ROHHAD patients were analyzed using a combination of next-generation and Sanger sequencing to identify exonic sequence variations in three genes: HCRT, HCRTR1, and HCRTR2.

Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD): exome sequencing of trios, monozygotic twins and tumours.

Background: Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is thought to be a genetic disease caused by de novo mutations, though causative mutations have yet to be identified. We searched for de novo coding mutations among a carefully-diagnosed and clinically homogeneous cohort of 35 ROHHAD patients.

Methods: We sequenced the exomes of seven ROHHAD trios, plus tumours from four of these patients and the unaffected monozygotic (MZ) twin of one (discovery cohort), to identify constitutional and somatic de novo sequence variants.