ABSTRACT
Context: ROHHAD syndrome presents a significant resemblance to HIDEA syndrome. The latter is caused by biallelic loss-of-function variants in the P4HTM gene and encompasses hypotonia, intellectual disabilities, eye abnormalities, hypoventilation, and dysautonomia. We report the first patient identified with HIDEA syndrome from our ROHHAD cohort. Clinical case: Our patient was a 21-month-old girl who had a history of severe respiratory infections requiring intensive care, hypotonia, abnormal eye movements, and rapid weight gain. Polysomnography identified severe central hypoventilation. During her follow-up, a significant psychomotor delay and the absence of language were gradually observed. The prolactin levels were initially increased. Hypothermia was reported at 4 years. Exome sequencing identified a new homozygous truncating P4HTM variant. Discussion: Our patient met the diagnosis criteria for ROHHAD, which included rapid weight gain, central hypoventilation appearing after 1.5 years of age, hyperprolactinemia suggesting hypothalamic dysfunction, and autonomic dysfunction manifesting as strabismus and hypothermia. However, she also presented with severe neurodevelopmental delay, which is not a classic feature of ROHHAD syndrome. HIDEA syndrome presents similarities with ROHHAD, including hypoventilation, obesity, and dysautonomia. To date, only 14% of endocrinological disturbances have been reported in HIDEA patients. Better delineation of both syndromes is required to investigate the eventual involvement of P4HTM, a regulator of calcium dynamics and gliotransmission, in ROHHAD patients. Conclusion: In the case of clinical evidence of ROHHAD in a child with abnormal neurological development or eye abnormalities, we suggest that the P4HTM gene be systematically interrogated in addition to the analysis of the PHOX2B gene. A better delineation of the natural history of HIDEA is required to allow further comparisons between features of HIDEA and ROHHAD. The clinical similarities could potentially orient some molecular hypotheses in the field of ROHHAD research.
ABSTRACT
A personal or family history of cancer has now become the primary cause of genetic consultations. In recent years, various genes have been identified that are associated with a more or less marked genetic predisposition to the development of cancers. The syndrome associated with the hereditary risk of breast and ovarian cancer and the Lynch syndrome are the most frequent ones, but there are many other, much less common, situations associated with familial cancer risk. In most cases, there are clear recommendations regarding the indications for genetic testing and the follow-up of patients identified as having a predisposition to cancer. At the CHU of Liège, we currently perform more than 1.400 oncogenetic consultations per year and we maintain a positivity rate of genetic tests performed in this indication higher than 10%. In this way, we allow a multidisciplinary care of patients with a high oncological risk and participate in a prevention and surveillance activity. We also pay increasing attention to the hereditary risk associated with pediatric cancers and to patients with multiple cancers, especially when these develop at an early age. Finally, the oncogenetic consultation must consider the psychological, ethical and legal aspects of a diagnosis that involves the patient and his or her future, but also the whole family.
Une histoire personnelle ou familiale de cancer est aujourd'hui devenue la première cause de consultation en génétique. Au cours de ces dernières années, en effet, différents gènes associés à une prédisposition génétique plus ou moins marquée au développement de pathologies cancéreuses ont été identifiés. Le syndrome de prédisposition héréditaire au cancer du sein et de l'ovaire (HBOC : Hereditary Breast and/or Ovarian Cancer) et le syndrome de Lynch sont les plus fréquents. Mais il existe une multitude d'autres situations beaucoup moins fréquentes associées à un risque familial de cancer. Dans la plupart des cas, des recommandations claires existent quant à l'indication des tests génétiques et quant au suivi proposé au patient chez qui une prédisposition au cancer est identifiée. Au CHU de Liège, nous réalisons actuellement plus de 1.400 consultations d'oncogénétique par an et nous maintenons un taux de positivité des tests génétiques réalisés dans cette indication supérieur à 10 %. De cette façon, nous permettons une prise en charge multidisciplinaire des patients avec un haut risque oncologique et participons à une activité de prévention et de surveillance. Nous portons une attention croissante aux enfants et adolescents présentant un cancer, d'une part, et aux adultes ayant présenté de multiples cancers, d'autre part, particulièrement lorsque ceux-ci se développent à un âge précoce. Enfin, la consultation d'oncogénétique doit tenir compte des aspects psychologiques, éthiques et légaux, liés à un diagnostic qui implique le patient et son avenir, mais également l'ensemble de la famille.
Subject(s)
Colorectal Neoplasms, Hereditary Nonpolyposis , Heredity , Ovarian Neoplasms , Child , Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Female , Genetic Predisposition to Disease , Genetic Testing , HumansABSTRACT
The gynaecological issues encountered in children and teenagers lay at the intersection of paediatric endocrinology and gynaecology. More than ten years ago, an outpatient clinic in paediatric endocrinology and gynaecology has been created. Here, we review the last 6 years. 214 girls were included, considering only the first visit for each patient. Collected data are initial concern for this consultation, age at first consultation and confirmed or suspected diagnosis. A classification is done according to the initial concern of patients in six categories. Principal queries concern pubertal development, precocious pilosity or abnormalities in menstrual cycles. Vulvovaginitis and morphologic abnormalities are also frequently encountered. This consultation suggests a paediatric approach with a child feeling confident and a gynaecological examination with a specialist knowing the anatomy particularities and the development of the children. This article focuses on the importance of specific gynaecological examination in children and reviews the main diseases encountered.
