Management of an older Marshall-Smith syndrome patient: a review of literature of MSS and craniosynostosis.

Marshall-Smith Syndrome (MSS) is a rare progressive developmental disorder that severely impairs a patient's intellectual development and physical health. The only known cause for MSS is a mutation in the nuclear factor 1 X (NFIX) gene. This mutation affects neuronal development and protein transcription.

Digenic inheritance involving a muscle-specific protein kinase and the giant titin protein causes a skeletal muscle myopathy.

In digenic inheritance, pathogenic variants in two genes must be inherited together to cause disease. Only very few examples of digenic inheritance have been described in the neuromuscular disease field. Here we show that predicted deleterious variants in SRPK3, encoding the X-linked serine/argenine protein kinase 3, lead to a progressive early onset skeletal muscle myopathy only when in combination with heterozygous variants in the TTN gene.

Long-term outcomes in ALG13-Congenital Disorder of Glycosylation.

ALG13-CDG is a rare X-linked disorder of N-linked glycosylation. Given the lack of long-term outcome data in ALG13-CDG, we collected natural history data and reviewed individuals surviving to young adulthood with confirmed pathogenic variants in ALG13 in our own cohort and in the literature. From the 14 ALG13-CDG patients enrolled into our Frontiers of Congenital Disorders of Glycosylation Consortium natural history study only two patients were older than 16 years; one of these two females is so far unreported.

Biallelic variants in ZNF142 lead to a syndromic neurodevelopmental disorder.

Biallelic variants of the gene encoding for the zinc-finger protein 142 (ZNF142) have recently been associated with intellectual disability (ID), speech impairment, seizures, and movement disorders in nine individuals from five families. In this study, we obtained phenotype and genotype information of 26 further individuals from 16 families. Among the 27 different ZNF142 variants identified in the total of 35 individuals only four were missense.

A Case of Growth Hormone Use in Dyggve-Melchior-Clausen Syndrome.

Short stature has many causes including genetic disease, skeletal dysplasias, endocrinopathies, familial short stature, and nutritional deficiencies. Recombinant growth hormone (rGH) therapy may be employed to improve stature based on the underlying etiology and growth velocity. Skeletal dysplasia in Dyggve-Melchior-Clausen (DMC) syndrome tends to be progressive, typically with hip involvement, and ultimately leads to bilateral dislocation of the hip joints.

Novel variants in KAT6B spectrum of disorders expand our knowledge of clinical manifestations and molecular mechanisms.

The phenotypic variability associated with pathogenic variants in Lysine Acetyltransferase 6B (KAT6B, a.k.a.

Wolf-Hirschhorn Syndrome with Hyperparathyroidism: A Case Report and a Narrative Review of the Literature.

Wolf-Hirschhorn syndrome (WHS) is a contiguous gene deletion condition. The WHS core phenotype includes developmental delays, intellectual disabilities, seizures, and distinctive facial features. Various other comorbidities have also been reported, such as hearing loss, heart defects, as well as eye problems and kidney problems.

A trauma-informed approach to the pediatric COVID-19 response.

To effectively care for children during COVID-19, pediatricians need to appreciate the stress and potential traumatic effect of the pandemic. By employing the "CARES" framework, pediatric providers can openly discuss the pandemic with patients and families, collaborate to build resiliency, and encourage engagement in activities and resources that are protective. This approach could potentially prevent both the short and long term health consequences resulting from the toxic stress and traumatic exposure of COVID-19.

Pulmonary Manifestations of Genetic Disorders in Children.

Congenital bronchopulmonary malformations are relatively common and arise during various periods of morphogenesis. Although some are isolated or sporadic occurrences, others may result from single gene mutations or cytogenetic imbalances. Single gene mutations have been identified, which are etiologically related to primary pulmonary hypoplasia, lung segmentation defects as well as pulmonary vascular and lymphatic lesions.

46,XY DSD and limb abnormalities in a female with a de novo LHX9 missense mutation.

Differences in sex development (DSD) are a group of rare conditions involving genes, hormones and reproductive organs, including genitals. Although these disorders are common, information about the molecular causes remain limited. Many genes have been identified in association with DSD but in many cases the causative gene could not be identified.

Beyond circles and squares: A commentary on updating pedigree nomenclature to better represent patient diversity.

With changes in our understanding of gender identity and disorders of sex differentiation (DSDs), as well as a need to promote medical care that appropriately reflects the intersectional personal identities of patients with respect to sex and gender, we explored possible modifications of pedigree nomenclature to better represent such patient diversity. There are currently no widely accepted standard symbols to simultaneously represent both gender identity and assigned sex at birth within a pedigree. Previous studies assessing perspectives from members of the transgender and gender non-binary (TGNB) community have highlighted the need for a unique symbol to represent non-binary individuals and better ways to represent core gender identities for gender minorities such as transgender individuals.

Adverse Childhood Experiences: A Case-Based Workshop Introducing Medical Students to Trauma-Informed Care.

Introduction: A large body of evidence implicates adverse childhood experiences (ACEs) as significant factors in shaping adult health outcomes. Despite their wide-ranging impact on health, training on ACEs is lacking in most medical school curricula. As part of a required health equity course for first-year medical students, we developed a novel workshop on ACEs with an introduction to protective effects of resilience and trauma-informed care.

A Case of Brown-Vialetto-Van Laere Syndrome Due To a Novel Mutation in Gene: Clinical Course and Response to Riboflavin.

Brown-Vialetto-Van Laere syndrome is a rare disorder characterized by motor, sensory, and cranial neuronopathies, associated with mutations in and genes that code for human riboflavin transporters RFVT2 and RFVT3, respectively. The authors describe the clinical course of a 6-year-old girl with Brown-Vialetto-Van Laere syndrome and a novel homozygous mutation c.1156T>C in the gene, who presented at the age of 2.

A Quality Improvement Collaborative to Improve Pediatric Primary Care Genetic Services.

Objective: To investigate if a national pediatric primary care quality improvement collaborative (QIC) could improve and sustain adherence with process measures related to diagnosis and management of children with genetic disorders.

Methods: Thirteen practices in 11 states from the American Academy of Pediatrics' Quality Improvement Innovation Networks participated in a 6-month QIC that included regular educational opportunities, access to genetic professionals, and performance feedback. The QIC identified 11 aims related to improving diagnosis and management of children with genetic disorders.

Pediatric resident debt and career intentions.

Objective: To examine current levels of educational debt among pediatric residents and the relationship between educational debt and career intentions.

Methods: Annual national random samples of 1000 graduating pediatric residents from 2006 through 2010 were surveyed. Responses were combined.

Tetrasomy 15q26: a distinct syndrome or Shprintzen-Goldberg syndrome phenocopy?

Purpose: The aim of this study was to characterize the clinical phenotype of patients with tetrasomy of the distal 15q chromosome in the form of a neocentric marker chromosome and to evaluate whether the phenotype represents a new clinical syndrome or is a phenocopy of Shprintzen-Goldberg syndrome.

Methods: We carried out comprehensive clinical evaluation of four patients who were identified with a supernumerary marker chromosome. The marker chromosome was characterized by G-banding, fluorescence in situ hybridization, single nucleotide polymorphism oligonucleotide microarray analysis, and immunofluorescence with antibodies to centromere protein C.

Diffuse peritoneal chlamydial infection presenting as possible ovarian peritoneal carcinomatosis in an adolescent female.

A 17-year-old girl presented with significant abdominal ascites associated with periumbilical pain. On examination, her abdomen was found to be soft and moderately distended with left lower quadrant tenderness. Abdominal computed tomographic scan demonstrated not only ascites but also diffuse peritoneal enhancement, a left-sided enhancing adnexal mass displacing the uterus to the right, as well as omental caking.

Pulmonary complications of genetic disorders.

Many different pulmonary manifestations are seen in conjunction with genetic disorders. Pulmonary findings have been noted with some cytogenetic conditions, many single gene or mendelian disorders, as well as with a number of inborn errors of metabolism. In addition, congenital lung anomalies are relatively common, occurring as isolated anomalies and as part of multiple anomaly syndromes.