Abstract Background In the last 20 years, substantial improvements have been made in the diagnosis, treatment and management of patients with Prader-Willi syndrome (PWS). Few data on causes of death are available since those improvements were made. Our study assessed the causes of death among French patients with PWS over the first 11 years of experience of the nationwide French Reference Center for PWS (FRC-PWS). Methods Our study relied on two sources of mortality information at national level between 2004 and 2014: The French Epidemiological Centre for the Medical Causes of Death (CépiDc) Registry and the FRC-PWS database. Causes of death were classified into seven categories: respiratory, cardiovascular, gastrointestinal, severe infection, sudden death, other causes, and unknown. Descriptive statistics were calculated separately for children (< 18 years-old) and adults (≥18 years-old). Results One hundred and four deaths were identified in France from 2004 to 2014. The median age at death was 30 years, ranging from less than 1 month to 58 years. Seventeen deaths occurred in patients under 18 years, with 70% of them in children under 2 years. Respiratory causes accounted for more than 50% of the deaths in patients with PWS in both children and adults. Both cause and age of death did not significantly differ according to gender or genetic subtype. Conclusions Patients with PWS die prematurely due to a respiratory cause in most cases at all ages. In those adult patients with data on obesity, 98% were reported to be obese.
Objetivo Realizar uma revisão sistemática da literatura acerca dos casos de endometriose que evoluem com obstrução intestinal dos últimos 5 anos, facilitando o reconhecimento dessa patologia na prática médica e o seu manejo adequado.
Abstract Upper airway obstruction is a common feature in pycnodysostosis and may cause obstructive sleep apnea (OSA). The aim of our study was to analyze sleep‐disordered breathing and respiratory management in children with pycnodysostosis. A retrospective review of the clinical charts and sleep studies of 10 consecutive children (three girls and seven boys) with pycnodysostosis seen over a time period of 10 years was performed. Six patients had severe OSA and/or nocturnal hypoventilation and were started on continuous positive airway pressure (CPAP) as a first treatment at a median age of 3.4 ± 2.6 years, because of the lack of indication of any surgical treatment. Three patients could be weaned after several years from CPAP after spontaneous improvement (two patients) or multiple upper airway surgeries (one patient). Three patients had upper airway surgery prior to their first sleep study with two patients still needing CPAP during their follow‐up. Only one patient never developed OSA. Patients with pycnodysostosis are at a high risk of severe OSA, underlying the importance of a systematic screening for sleep‐disordered breathing. Multidisciplinary care is mandatory because of the multilevel airway obstruction. CPAP is very effective and well accepted for treating OSA.
The detection of pituitary stalk interruption syndrome (PSIS) by magnetic resonance imaging is a diagnostic marker of permanent GH deficiency (GHD), but the pathogenesis of PSIS is unknown. Fifty-one patients (27 males) with GHD and PSIS were classified according to whether the GHD was isolated (group 1, 16 cases) or associated with other anterior pituitary abnormalities (group 2, 35 cases). The 2 groups had similar characteristics (frequencies of perinatal abnormalities, ages at occurrence of first signs and at diagnosis, height, GH peak response to stimuli other than GHRH), but associated malformations were less frequent in group 1 (12%) than in group 2 (54%; P < 0.01), hypoglycemia occurred in 25% of group 1 and 70% of group 2 (P < 0.01), and the GH peak response to GHRH was less than 10 μg/L in 0% of group 1 (4 cases evaluated) and 57% of group 2 (21 cases; P < 0.05). Thirty-one cases (61%; 25 from group 2) had features suggesting an antenatal origin: familial form (4 cases), microphallus (10 boys), and/or associated malformations (50%; 21 cases). Twenty-seven cases (53%, 22 from group 2) had features suggesting a hypothalamic origin. The three group 1 patients with a GH peak of 1 μg/L or less had no large GH-N gene deletion. One familial form had no linkage between the GHD phenotype and abnormal GH-N locus, and the only mutation described to date in the GHRH receptor gene was absent. The two patients with low plasma PRL levels had no Pit-1 gene abnormality. Thus, most of the patients with GHD associated with multiple anterior pituitary abnormalities and PSIS have features suggesting an antenatal origin. The GH-N, GHRH receptor, and Pit-1 genes do not seem to be implicated in PSIS.
Abstract Objective ACTH-independent Cushing’s syndrome (CS) in children is very rare but potentially fatal. In bilateral nodular hyperplasia, synchronous bilateral adrenalectomy (SBA) represents the definitive treatment to correct hypercortisolism. We aim to report the multidisciplinary management of this rare condition. Methods Presentation, management, and outcomes of all children with ACTH-independent CS who underwent SBA in a tertiary reference centre between 1992-2022 were retrospectively analysed. Results Ten children were included: six with McCune Albright syndrome, four with primary pigmented nodular adrenocortical disease (three with Carney complex). Presentation varied according to age at diagnosis. In infants (n=7), failure to thrive with anorexia (n=7), cushingoid facies (n=7), arterial hypertension (n=6), hypotonia (n=5), hyperglycaemia (n=4), liver dysfunction (n=4), and hypercalcemia with nephrocalcinosis (n=4) were the main reasons for urgent hospitalization. Prepubertal children (n=3) presented with linear growth arrest associated with obesity, cushingoid facies, and hirsutism. SBA was indicated in severe neonatal hypercortisolism, or in those that were non-responsive to medical treatment. SBA was performed by robot-assisted laparoscopy (n=6), laparoscopy (n=2) or laparotomy (n=2). One post-operative complication occurred (seroma in the adrenal bed). During follow-up (median: 4.8 years) no deaths or acute adrenal crisis occurred. Conclusion Paediatric CS must be referred to a paediatric centre with medical and surgical expertise. Shared-decision making regarding SBA must be prompt to allow rapid cure of CS, even if it implies lifelong steroid replacement. This avoids long-term complications of hypercortisolism, particularly cognitive decline. Robot-assisted SBA is feasible and safe, even in infants when performed by an experienced robotic team.
