Pigmentation abnormalities in Coffin-Siris syndrome.

Pigmentary abnormalities in Coffin-Siris Syndrome should be considered as part of the wide phenotypical spectrum of this patients.

Body composition in patients with congenital myotonic dystrophy.

INTRODUCTION: Congenital myotonic dystrophy (CDM) is a rare neuromuscular disorder characterized by severe hypotonia and muscle weakness at birth that tends to improve with age. Understanding lean body and bone mass in this population has important research and clinical implications. The main objective of this study was to determine whether older children with CDM had muscle mass similar to healthy controls. METHODS: Thirty-five patients with CDM (3-13 years old) were enrolled. We analyzed lean body mass (LBM) and bone mineral content using the mechanostat framework, which allows calculation of z-scores for sex, age, and height. RESULTS: All patients had low LBM z-scores (muscle mass); however, higher LBM z-score was positively correlated with age (r = 0.45, P = 0.006), showing that it is closer to normal in older patients. DISCUSSION: Unlike other neuromuscular diseases, older children with CDM have a muscle mass closer to age-matched controls, consistent with the clinical profile of increasing strength in childhood. Muscle Nerve 60: 176-179, 2019.

"Cancer in ARID1A-Coffin-Siris syndrome: Review and report of a child with hepatoblastoma".

Coffin-Siris syndrome (CSS) is a rare neurodevelopmental and multisystemic disorder with wide genetic heterogeneity and phenotypic variability caused by pathogenic variants in the BAF complex with 341 cases enrolled in the CSS/BAF-related disorders registry by 2021. Pathogenic variants of ARID1A account for 7-8% of cases with CSS phenotype. Malignancy has been previously reported in six individuals with CSS associated with BAF mutations. Two of these malignancies including one acute lymphoid leukemia and one hepatoblastoma were reported in ARID1A-associated CSS (ARID1A-CSS). Alterations in ARID1A are among the most common molecular aberrations in human cancer. Somatic deletion of 1p and specifically of 1p36.11 containing ARID1A is frequently seen in hepatoblastoma and has been associated with high-risk features. Here we report a child with CSS Phenotype and a novel de novo variant of ARID1A with hepatoblastoma. Because hepatoblastoma has an incidence of 1 per million children, the presence of hepatoblastoma in 2 of 30 known cases of ARID1A-CSS is significant. ARID1A-CSS should be included among the cancer predisposition syndromes associated with an increased risk of hepatoblastoma and tumour surveillance considered for these patients. The role of ARID1A in the pathogenesis and outcome of hepatoblastoma deserves further investigation.

A Phenotypic Description of Congenital Myotonic Dystrophy using PhenoStacks.

BACKGROUND: Congenital Myotonic Dystrophy (CDM1) is a rare neuromuscular condition caused by a triplet repeat expansion in the DMPK gene. Despite there being a well-recognized clinical syndrome, there has not been an effort to use a standardized ontology system to describe the disease characteristics in existing literature. Thus, comparing or contrasting different cohorts from the literature can be challenging, and coding disease features for clinical research or for registry data items is not uniform. PhenoStacks is a visualization analytics tool which helps graphically illustrate phenotypes of patients with genetic disorders using Human Phenotype Ontology (HPO) terms and can sort phenotypes by different disease characteristics. OBJECTIVE: To demonstrate the efficacy of PhenoStacks and the HPO system as clinical research tools when describing CDM1 cohorts. METHODS: Health Endpoints and Longitudinal progression in congenital myotonic dystrophy (HELP-CDM) is an ongoing study which longitudinally follows patients with CDM1. Items from the HELP-CDM data sheet were matched to corresponding HPO terms and analyzed using PhenoStacks. RESULTS: In total 40 subjects' phenotypes were visualized through PhenoStacks and 73 HPO terms were used for the analysis. Frequent phenotypic features included "high narrow palate", "facial palsy", "ptosis", "hyporeflexia", and "weak voice". Contractures were associated with higher repeat sizes. Hypoplastic muscles and infantile axial hypotonia were more frequently observed in infants. CONCLUSIONS: PhenoStacks is a valuable clinical and scientific tool as it identifies variability within cohorts and highlights significant phenotypic features.

Prenatal, Neonatal, and Early Childhood Features in Congenital Myotonic Dystrophy.

BACKGROUND: Congenital myotonic dystrophy (CDM) is the neonatal onset and most severe presentation of Myotonic Dystrophy type 1. Since it first description, perinatal complications have been detailed including prolonged hospital stay, respiratory and feeding therapy during the neonatal period, although long-term complications are less documented. OBJECTIVE: Present a prospective cohort of CDM and compare it to the literature of other CDM case series, to adequately describe and contrast the prenatal, neonatal and infancy features of CDM. METHODS: A 5-year cohort of CDM eligible cases was conducted via the Canadian Pediatric Surveillance Program. 38 patients met the inclusion criteria. Comparison to other CDM case series published in the literature between 1992 and 2016 about perinatal and infancy morbidity. RESULT: From a total of 118 cases, the most frequent features were Polyhydramnios (58%), feeding therapy (77%), intubation and ventilation (58%); neonatal death was reported in 16% of the cases; the most frequent long-term morbidity were respiratory tract infections. CONCLUSIONS: We performed a detailed description of the main perinatal features of CDM and precise documentation of the mortality and morbidity during the first five years of life. This is an essential step in the knowledge of the natural history of CDM.