Siblings With Congenital Hyperinsulinism From Possible Parental Gonadal Mosaicism.

Congenital hyperinsulinism is the most common cause of persistent hypoglycemia in early infancy. Mutations in the gene for heterozygous hepatocyte nuclear transcription factor 4-alpha () account for approximately 5% of cases and are inherited in an autosomal dominant fashion or arise as de novo mutations. This case describes a unique presentation of parental gonadal, or germline, mosaicism as the suspected inheritance pattern for siblings with congenital hyperinsulinism caused by mutations.

Multiple Fractures in an Infant With Hepatoblastoma and Beckwith-Wiedemann Syndrome.

Children with hepatoblastoma have an increased incidence of fractures, but data are limited. Previous reports document an average of 4 fractures per child with hepatoblastoma. We present a severe case of a premature 4-month-old with multiple fractures in the setting of Beckwith-Wiedemann syndrome and hepatoblastoma.

Nutritional rickets masquerading as spinal muscular atrophy type III.

Muscle atrophy, weakness, and loss of ambulation in the pediatric population are signs of progressive neuromuscular diseases. Rapid identification of such diseases is important to prevent further progression. In pediatric neurology, it is well understood to include neuromuscular disorders in the differential for such presentations.

Predictors of Psychosocial Distress in Parents of Young Children with Disorders of Sex Development.

Purpose: We evaluated demographic, financial and support predictors of distress for parents of young children with disorders of sex development including atypical genital development, and characterized early parental experiences. This work extends our previous findings to identify those parents at risk for distress.

Materials And Methods: Participants included mothers (76) and fathers (63) of a child (78) diagnosed with disorders of sex development characterized by moderate to severe genital atypia.

TESTICULAR REGRESSION SYNDROME: PRACTICE VARIATION IN DIAGNOSIS AND MANAGEMENT.

The purpose of this study was to assess clinical practice patterns with regard to diagnosis and management of testicular regression syndrome (TRS), a condition in 46,XY males with male phenotypic genitalia and bilateral absence of testes. A retrospective review was conducted at two large pediatric academic centers to examine diagnostic and management approaches for TRS. Records of 57 patients were reviewed.

Management of pediatric patients with DSD and ambiguous genitalia: Balancing the child's moral claims to self-determination with parental values and preferences.

Introduction: A central ethical dilemma in management of the patient with a disorder of sex development (DSD) is the potential conflict between respect for the fundamental right of the child for physical and emotional integrity and self-determination, and the right of parents to serve as surrogate decision-makers and act in their child's best interest.

Methods: Over the past 2 years we have encountered three complex DSD cases on the spectrum of mixed gonadal dysgenesis to ovotesticular DSD in which gender assignment and therefore optimal surgical management was uncertain. All patients had mosaic karyotypes with Y chromosome, dysgenetic ovary and dysgenetic testis, a urogenital sinus, and prominent phallus.

Clinical Characterization of Patients With Autosomal Dominant Short Stature due to Aggrecan Mutations.

Context: Heterozygous mutations in the aggrecan gene (ACAN) cause autosomal dominant short stature with accelerated skeletal maturation.

Objective: We sought to characterize the phenotypic spectrum and response to growth-promoting therapies.

Patients And Methods: One hundred three individuals (57 females, 46 males) from 20 families with autosomal dominant short stature and heterozygous ACAN mutations were identified and confirmed using whole-exome sequencing, targeted next-generation sequencing, and/or Sanger sequencing.

A 46,XX Ovotesticular Disorder of Sex Development Likely Caused by a Steroidogenic Factor-1 (NR5A1) Variant.

Background: A variant in steroidogenic factor-1 (SF-1, encoded by the gene NR5A1), p.Arg92Trp, has recently been reported in multiple families with 46,XX ovotesticular or testicular disorders of sex development (DSD). This amino acid change impacts the DNA-binding domain and perturbs gonadal differentiation pathways.

Recent findings on the genetics of disorders of sex development.

Purpose Of Review: Disorders of sex development (DSD) are a diverse group of conditions affecting gonadal development, sexual differentiation, or chromosomal sex. In this review, we will discuss recent literature on the genetic causes of DSD, with a focus on novel genetic sequencing technologies, new phenotypes associated with known DSD genes, and increasing recognition of the role of genetic regulatory elements in DSD.

Recent Findings: We performed a comprehensive search of PubMed through August 2016 to identify important peer-reviewed publications from 2015 to 2016 on the topic of DSD genetics.

Two Unrelated Undervirilized 46,XY Males with Inherited NR5A1 Variants Identified by Whole-Exome Sequencing.

Background: Undervirilized 46,XY males with bifid scrotum often pose a diagnostic challenge, and the majority of cases typically do not receive a genetic diagnosis. NR5A1 mutations can be seen in 10-20% of the cases and are a relatively common cause of undervirilization.

Methods: Whole-exome sequencing was utilized to study 10 undervirilized 46,XY subjects with bifid scrotum.

Initial Management of Disorders of Sex Development in Newborns.

Disorders of sex development are challenging to evaluate and diagnose in the newborn. As pediatric urologists, our goals are to (1) identify patients who should be evaluated; (2) rule out life-threatening syndromes; and (3) involve a multidisciplinary team for evaluation, diagnosis, and gender assignment. This review briefly goes over the newborn differential diagnosis in disorders of sex development, highlights the important laboratory and imaging data needed, and discusses the multidisciplinary approach to gender assignment and care of these patients.

Ten Sites, 10 Years, 10 Lessons: Scale-up of Routine HIV Testing at Community Health Centers in the Bronx, New York.

Objective: In response to the current CDC recommendations for routine HIV testing in clinical settings, the Adolescent AIDS Program at Montefiore Medical Center in the Bronx, New York, developed the Advise, Consent, Test, Support routine HIV testing model (ACTS) in 2003. ACTS was piloted in 10 community health centers operated by Montefiore because they serve populations most at risk for HIV/AIDS.

Methods: ACTS streamlined and codified the counseling and testing process, provided a routine HIV testing practice change plan, and provided training and communication materials that promoted routine HIV testing.

A novel ERCC6 splicing variant associated with a mild Cockayne syndrome phenotype.

Background: Cockayne syndrome is an autosomal recessive, heterogeneous syndrome with classical features, including short stature, microcephaly, developmental delay, neuropathy, and photosensitivity. New genomic approaches offer improved molecular diagnostic potential.

Methods: Whole-exome sequencing was employed to study a consanguineous extended family with severe short stature and variable presentations of peripheral neuropathy, lipoatrophy, photosensitivity, webbed neck, and hirsutism.

Eosinophils from lineage-ablated Delta dblGATA bone marrow progenitors: the dblGATA enhancer in the promoter of GATA-1 is not essential for differentiation ex vivo.

A critical role for eosinophils in remodeling of allergic airways was observed in vivo upon disruption of the dblGATA enhancer that regulates expression of GATA-1, which resulted in an eosinophil-deficient phenotype in the DeltadblGATA mouse. We demonstrate here that bone marrow progenitors isolated from DeltadblGATA mice can differentiate into mature eosinophils when subjected to cytokine stimulation ex vivo. Cultured DeltadblGATA eosinophils contain cytoplasmic granules with immunoreactive major basic protein and they express surface Siglec F and transcripts encoding major basic protein, eosinophil peroxidase, and GATA-1, -2, and -3 to an extent indistinguishable from cultured wild-type eosinophils.

Schistosoma mansoni infection in eosinophil lineage-ablated mice.

We explore the controversial issue of the role of eosinophils in host defense against helminthic parasites using the established Schistosoma mansoni infection model in 2 novel mouse models of eosinophil lineage ablation (DeltadblGATA and TgPHIL). No eosinophils were detected in bone marrow of infected DeltadblGATA or TgPHIL mice, despite the fact that serum IL-5 levels in these infected mice exceeded those in infected wild type by approximately 4-fold. Liver granulomata from infected DeltadblGATA and TgPHIL mice were likewise depleted of eosinophils compared with those from their respective wild types.

Plasminogen activator inhibitor-2 (PAI-2) in eosinophilic leukocytes.

Plasminogen activator inhibitor-2 (PAI-2) as a potential eosinophil protein was inferred from our gene microarray study of mouse eosinophilopoiesis. Here, we detect 47 kDa intracellular and approximately 60 kDa secretory forms of PAI-2 in purified human eosinophil extracts. PAI-2 is present at variable concentrations in eosinophil lysates, ranging from 30 to 444 ng/10(6) cells, with a mean of 182 ng/10(6) cells from 10 normal donors, which is the highest per-cell concentration among all leukocyte subtypes evaluated.

The Human Cloning Prohibition Act of 2001: vagueness and federalism.

On July 31, 2001, the U.S. House of Representatives passed The Human Cloning Prohibition Act of 2001.