ROHHAD syndrome without rapid-onset obesity: A diagnosis challenge

peer reviewedBackgroundROHHAD syndrome (Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation and Autonomic Dysregulation) is rare. Rapid-onset morbid obesity is usually the first recognizable sign of this syndrome, however a subset of patients develop ROHHAD syndrome without obesity. The prevalence of this entity is currently unknown. Alteration of respiratory control as well as dysautonomic disorders often have a fatal outcome, thus early recognition of this syndrome is essential.Material and methodsA retrospective, observational, multicenter study including all cases of ROHHAD without rapid-onset obesity diagnosed in France from 2000 to 2020.ResultsFour patients were identified. Median age at diagnosis was 8 years 10 months. Median body mass index was 17.4 kg/m2. Signs of autonomic dysfunction presented first, followed by hypothalamic disorders. All four patients had sleep apnea syndrome. Hypoventilation led to the diagnosis. Three of the four children received ventilatory support, all four received hormone replacement therapy, and two received psychotropic treatment. One child in our cohort died at 2 years 10 months old. For the three surviving patients, median duration of follow-up was 7.4 years.ConclusionROHHAD syndrome without rapid-onset obesity is a particular entity, appearing later than ROHHAD with obesity. This entity should be considered in the presence of dysautonomia disorders without brain damage. Likewise, the occurrence of a hypothalamic syndrome with no identified etiology requires a sleep study to search for apnea and hypoventilation. The identification of ROHHAD syndrome without rapid-onset obesity is a clinical challenge, with major implications for patient prognosis

Multi-Locus Phylogeographic and Population Genetic Analysis of Anolis carolinensis: Historical Demography of a Genomic Model Species

The green anole (Anolis carolinensis) has been widely used as an animal model in physiology and neurobiology but has recently emerged as an important genomic model. The recent sequencing of its genome has shed new light on the evolution of vertebrate genomes and on the process that govern species diversification. Surprisingly, the patterns of genetic diversity within natural populations of this widespread and abundant North American lizard remain relatively unknown. In the present study, we use 10 novel nuclear DNA sequence loci (N = 62 to 152) and one mitochondrial locus (N = 226) to delimit green anole populations and infer their historical demography. We uncovered four evolutionarily distinct and geographically restricted lineages of green anoles using phylogenetics, Bayesian clustering, and genetic distance methods. Molecular dating indicates that these lineages last shared a common ancestor ∼2 million years ago. Summary statistics and analysis of the frequency distributions of DNA polymorphisms strongly suggest range-wide expansions in population size. Using Bayesian Skyline Plots, we inferred the timing of population size expansions, which differ across lineages, and found evidence for a relatively recent and rapid westward expansion of green anoles across the Gulf Coastal Plain during the mid-Pleistocene. One surprising result is that the distribution of genetic diversity is not consistent with a latitudinal shift caused by climatic oscillations as is observed for many co-distributed taxa. This suggests that the most recent Pleistocene glacial cycles had a limited impact on the geographic distribution of the green anole at the northern limits of its range

Table_1_ROHHAD syndrome without rapid-onset obesity: A diagnosis challenge.docx

BackgroundROHHAD syndrome (Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation and Autonomic Dysregulation) is rare. Rapid-onset morbid obesity is usually the first recognizable sign of this syndrome, however a subset of patients develop ROHHAD syndrome without obesity. The prevalence of this entity is currently unknown. Alteration of respiratory control as well as dysautonomic disorders often have a fatal outcome, thus early recognition of this syndrome is essential.Material and methodsA retrospective, observational, multicenter study including all cases of ROHHAD without rapid-onset obesity diagnosed in France from 2000 to 2020.ResultsFour patients were identified. Median age at diagnosis was 8 years 10 months. Median body mass index was 17.4 kg/m2. Signs of autonomic dysfunction presented first, followed by hypothalamic disorders. All four patients had sleep apnea syndrome. Hypoventilation led to the diagnosis. Three of the four children received ventilatory support, all four received hormone replacement therapy, and two received psychotropic treatment. One child in our cohort died at 2 years 10 months old. For the three surviving patients, median duration of follow-up was 7.4 years.ConclusionROHHAD syndrome without rapid-onset obesity is a particular entity, appearing later than ROHHAD with obesity. This entity should be considered in the presence of dysautonomia disorders without brain damage. Likewise, the occurrence of a hypothalamic syndrome with no identified etiology requires a sleep study to search for apnea and hypoventilation. The identification of ROHHAD syndrome without rapid-onset obesity is a clinical challenge, with major implications for patient prognosis.</p

Similarities and differences of interstitial lung disease associated with pathogenic variants in SFTPC and ABCA3 in adults

International audienceAbstract Background and Objective Variants in surfactant genes SFTPC or ABCA3 are responsible for interstitial lung disease (ILD) in children and adults, with few studies in adults. Methods We conducted a multicentre retrospective study of all consecutive adult patients diagnosed with ILD associated with variants in SFTPC or ABCA3 in the French rare pulmonary diseases network, OrphaLung. Variants and chest computed tomography (CT) features were centrally reviewed. Results We included 36 patients (median age: 34 years, 20 males), 22 in the SFTPC group and 14 in the ABCA3 group. Clinical characteristics were similar between groups. Baseline median FVC was 59% ([52–72]) and DLco was 44% ([35–50]). An unclassifiable pattern of fibrosing ILD was the most frequent on chest CT, found in 85% of patients, however with a distinct phenotype with ground‐glass opacities and/or cysts. Nonspecific interstitial pneumonia and usual interstitial pneumonia were the most common histological patterns in the ABCA3 group and in the SFTPC group, respectively. Annually, FVC and DL CO declined by 1.87% and 2.43% in the SFTPC group, respectively, and by 0.72% and 0.95% in the ABCA3 group, respectively (FVC, p = 0.014 and DL CO , p = 0.004 for comparison between groups). Median time to death or lung transplantation was 10 years in the SFTPC group and was not reached at the end of follow‐up in the ABCA3 group. Conclusion SFTPC and ABCA3 ‐associated ILD present with a distinct phenotype and prognosis. A radiologic pattern of fibrosing ILD with ground‐glass opacities and/or cysts is frequently found in these rare conditions

Phenotypic characterization of interstitial lung disease associated with mutations inSFTPC and ABCA3 in adults

International audienceIntroduction: Mutations in surfactant genes SFTPC or ABCA3 are responsible for interstitial lung disease (ILD) in children and adults. Despite numerous paediatric data, few studies described these entities in adults.Methods: We conducted a multicenter retrospective study of adult patients with ILD associated with mutations in SFTPC or ABCA3 in the French rare pulmonary diseases network OrphaLung.Results: We included 36 patients, 22 in the SFTPC group and 14 in the ABCA3 group. Clinical characteristics were similar between the two groups. Baseline pulmonary function tests reported a median FVC of 59% ([52 – 72]%), a median FEV1 of 63% ([48,3 – 73,3] %), a median TLC of 65 % ([59 – 76] %) and a median DLco of 44 % ([35,4 – 50] %). A pattern of unclassifiable fibrosing ILD was the most frequent on chest computed tomography, found in 85% of patients. Nonspecific interstitial pneumonia and usual interstitial pneumonia were the most common histological patterns in the ABCA3 group and in the SFTPC group, respectively. Median survival before death or lung transplantation was 10 years in the SFTPC group (4 deaths and 8 patients with lung transplantation) and was not reached at the end of follow-up in the ABCA3 group (1 death and 2 patients with lung transplantation).Conclusion: Patients with ILD and mutations in SFTPC or ABCA3 present a distinct phenotype of unclassifiable fibrosing ILD with cysts and ground glass opacities, and their prognosis is often severe. While our results highlight the phenotypical heterogeneity of these patients, they also expand our knowledge of these rare causes of ILD in adult

Phenotypic characterization of interstitial lung disease associated with mutations inSFTPC and ABCA3 in adults

International audienceIntroduction: Mutations in surfactant genes SFTPC or ABCA3 are responsible for interstitial lung disease (ILD) in children and adults. Despite numerous paediatric data, few studies described these entities in adults.Methods: We conducted a multicenter retrospective study of adult patients with ILD associated with mutations in SFTPC or ABCA3 in the French rare pulmonary diseases network OrphaLung.Results: We included 36 patients, 22 in the SFTPC group and 14 in the ABCA3 group. Clinical characteristics were similar between the two groups. Baseline pulmonary function tests reported a median FVC of 59% ([52 – 72]%), a median FEV1 of 63% ([48,3 – 73,3] %), a median TLC of 65 % ([59 – 76] %) and a median DLco of 44 % ([35,4 – 50] %). A pattern of unclassifiable fibrosing ILD was the most frequent on chest computed tomography, found in 85% of patients. Nonspecific interstitial pneumonia and usual interstitial pneumonia were the most common histological patterns in the ABCA3 group and in the SFTPC group, respectively. Median survival before death or lung transplantation was 10 years in the SFTPC group (4 deaths and 8 patients with lung transplantation) and was not reached at the end of follow-up in the ABCA3 group (1 death and 2 patients with lung transplantation).Conclusion: Patients with ILD and mutations in SFTPC or ABCA3 present a distinct phenotype of unclassifiable fibrosing ILD with cysts and ground glass opacities, and their prognosis is often severe. While our results highlight the phenotypical heterogeneity of these patients, they also expand our knowledge of these rare causes of ILD in adult

Phenotypic characterization of interstitial lung disease associated with mutations inSFTPC and ABCA3 in adults

International audienceIntroduction: Mutations in surfactant genes SFTPC or ABCA3 are responsible for interstitial lung disease (ILD) in children and adults. Despite numerous paediatric data, few studies described these entities in adults.Methods: We conducted a multicenter retrospective study of adult patients with ILD associated with mutations in SFTPC or ABCA3 in the French rare pulmonary diseases network OrphaLung.Results: We included 36 patients, 22 in the SFTPC group and 14 in the ABCA3 group. Clinical characteristics were similar between the two groups. Baseline pulmonary function tests reported a median FVC of 59% ([52 – 72]%), a median FEV1 of 63% ([48,3 – 73,3] %), a median TLC of 65 % ([59 – 76] %) and a median DLco of 44 % ([35,4 – 50] %). A pattern of unclassifiable fibrosing ILD was the most frequent on chest computed tomography, found in 85% of patients. Nonspecific interstitial pneumonia and usual interstitial pneumonia were the most common histological patterns in the ABCA3 group and in the SFTPC group, respectively. Median survival before death or lung transplantation was 10 years in the SFTPC group (4 deaths and 8 patients with lung transplantation) and was not reached at the end of follow-up in the ABCA3 group (1 death and 2 patients with lung transplantation).Conclusion: Patients with ILD and mutations in SFTPC or ABCA3 present a distinct phenotype of unclassifiable fibrosing ILD with cysts and ground glass opacities, and their prognosis is often severe. While our results highlight the phenotypical heterogeneity of these patients, they also expand our knowledge of these rare causes of ILD in adult

Phenotypic characterization of interstitial lung disease associated with mutations inSFTPC and ABCA3 in adults

International audienceIntroduction: Mutations in surfactant genes SFTPC or ABCA3 are responsible for interstitial lung disease (ILD) in children and adults. Despite numerous paediatric data, few studies described these entities in adults.Methods: We conducted a multicenter retrospective study of adult patients with ILD associated with mutations in SFTPC or ABCA3 in the French rare pulmonary diseases network OrphaLung.Results: We included 36 patients, 22 in the SFTPC group and 14 in the ABCA3 group. Clinical characteristics were similar between the two groups. Baseline pulmonary function tests reported a median FVC of 59% ([52 – 72]%), a median FEV1 of 63% ([48,3 – 73,3] %), a median TLC of 65 % ([59 – 76] %) and a median DLco of 44 % ([35,4 – 50] %). A pattern of unclassifiable fibrosing ILD was the most frequent on chest computed tomography, found in 85% of patients. Nonspecific interstitial pneumonia and usual interstitial pneumonia were the most common histological patterns in the ABCA3 group and in the SFTPC group, respectively. Median survival before death or lung transplantation was 10 years in the SFTPC group (4 deaths and 8 patients with lung transplantation) and was not reached at the end of follow-up in the ABCA3 group (1 death and 2 patients with lung transplantation).Conclusion: Patients with ILD and mutations in SFTPC or ABCA3 present a distinct phenotype of unclassifiable fibrosing ILD with cysts and ground glass opacities, and their prognosis is often severe. While our results highlight the phenotypical heterogeneity of these patients, they also expand our knowledge of these rare causes of ILD in adult