Persistent Gynecomastia due to Short-term Low-dose Finasteride for Androgenetic Alopecia.

We report a case of persistent gynecomastia in a healthy 20-year-old man after 1 month of low-dose finasteride. Finasteride was discontinued after 2 months, and gynecomastia was unchanged 5 months after drug withdrawal. The gynecomastia regressed but did not resolve after 6 months of treatment with raloxifene, a selective estrogen receptor modulator.

The Association of Accelerated Early Growth, Timing of Puberty, and Metabolic Consequences in Children.

Accelerated early growth and early timing of puberty or pubertal variant have been noticed as risk factors for metabolic syndrome, more frequently observed in children born small for gestational age (SGA) or children with premature adrenarche (PA). Children with SGA, especially if they make an accelerated catch-up growth in early life, carry a higher risk for long-term metabolic consequences, such as type 2 diabetes, insulin resistance, and cardiovascular diseases. Furthermore, multiple studies support that these children, either born SGA or with a history of PA, may have earlier pubertal timing, which is also associated with various metabolic risks.

Loss-of-function variant in SPIN4 causes an X-linked overgrowth syndrome.

Overgrowth syndromes can be caused by pathogenic genetic variants in epigenetic writers, such as DNA and histone methyltransferases. However, no overgrowth disorder has previously been ascribed to variants in a gene that acts primarily as an epigenetic reader. Here, we studied a male individual with generalized overgrowth of prenatal onset.

Effect of stimulants on final adult height.

Background: The use of stimulant medications for treatment of ADHD has raised concern as to whether they adversely impact linear growth. Previous studies have indicated that stimulant medications may suppress growth for a short period after treatment initiation; however, more information is needed to evaluate the long-term effects on final adult stature. This mini review aims to evaluate the effect of stimulant medications on final adult height in children with ADHD.

A neomorphic variant in SP7 alters sequence specificity and causes a high-turnover bone disorder.

SP7/Osterix is a transcription factor critical for osteoblast maturation and bone formation. Homozygous loss-of-function mutations in SP7 cause osteogenesis imperfecta type XII, but neomorphic (gain-of-new-function) mutations of SP7 have not been reported in humans. Here we describe a de novo dominant neomorphic missense variant (c.

Evidence That the Etiology of Congenital Hypopituitarism Has a Major Genetic Component but Is Infrequently Monogenic.

Purpose: Congenital hypopituitarism usually occurs sporadically. In most patients, the etiology remains unknown.

Methods: We studied 13 children with sporadic congenital hypopituitarism.

Genetic evaluation in children with short stature.

Purpose Of Review: Short stature is a common clinical manifestation in children. Yet, a cause is often unidentifiable in the majority of children with short stature by a routine screening approach. The purpose of this review is to describe the optimal genetic approach for evaluating short stature, challenges of genetic testing, and recent advances in genetic testing for short stature.

DLG2 variants in patients with pubertal disorders.

Purpose: Impaired function of gonadotropin-releasing hormone (GnRH) neurons can cause a phenotypic spectrum ranging from delayed puberty to isolated hypogonadotropic hypogonadism (IHH). We sought to identify a new genetic etiology for these conditions.

Methods: Exome sequencing was performed in an extended family with autosomal dominant, markedly delayed puberty.

Plasma midkine concentrations in healthy children, children with increased and decreased adiposity, and children with short stature.

Background: Midkine (MDK), one of the heparin-binding growth factors, is highly expressed in multiple organs during embryogenesis. Plasma concentrations have been reported to be elevated in patients with a variety of malignancies, in adults with obesity, and in children with short stature, diabetes, and obesity. However, the concentrations in healthy children and their relationships to age, nutrition, and linear growth have not been well studied.

Genetic regulation of linear growth.

Linear growth occurs at the growth plate. Therefore, genetic defects that interfere with the normal function of the growth plate can cause linear growth disorders. Many genetic causes of growth disorders have already been identified in humans.

QRICH1 mutations cause a chondrodysplasia with developmental delay.

In many children with short stature, the etiology of the decreased linear growth remains unknown. We sought to identify the underlying genetic etiology in a patient with short stature, irregular growth plates of the proximal phalanges, developmental delay, and mildly dysmorphic facial features. Exome sequencing identified a de novo, heterozygous, nonsense mutation (c.

Evaluation of Recipients of Positive and Negative Secondary Findings Evaluations in a Hybrid CLIA-Research Sequencing Pilot.

While consensus regarding the return of secondary genomic findings in the clinical setting has been reached, debate about such findings in the research setting remains. We developed a hybrid, research-clinical translational genomics process for research exome data coupled with a CLIA-validated secondary findings analysis. Eleven intramural investigators from ten institutes at the National Institutes of Health piloted this process.

Differential aging of growth plate cartilage underlies differences in bone length and thus helps determine skeletal proportions.

Bones at different anatomical locations vary dramatically in size. For example, human femurs are 20-fold longer than the phalanges in the fingers and toes. The mechanisms responsible for these size differences are poorly understood.

New developments in the genetic diagnosis of short stature.

Purpose Of Review: Genome-wide approaches including genome-wide association studies as well as exome and genome sequencing represent powerful new approaches that have improved our ability to identify genetic causes of human disorders. The purpose of this review is to describe recent advances in the genetic causes of short stature.

Recent Findings: In addition to SHOX deficiency which is one of the most common causes of isolated short stature, PAPPA2, ACAN, NPPC, NPR2, PTPN11 (and other rasopathies), FBN1, IHH and BMP2 have been identified in isolated growth disorders with or without other mild skeletal findings.

mir-374-5p, mir-379-5p, and mir-503-5p Regulate Proliferation and Hypertrophic Differentiation of Growth Plate Chondrocytes in Male Rats.

Growth plate chondrocytes undergo sequential differentiation to form the resting zone, the proliferative zone (PZ), and the hypertrophic zone (HZ). The important role of microRNAs (miRNAs) in the growth plate was previously revealed by cartilage-specific ablation of Dicer, an enzyme essential for biogenesis of many miRNAs. To identify specific miRNAs that regulate differentiation of PZ chondrocytes to HZ chondrocytes, we microdissected individual growth plate zones from juvenile rats and performed miRNA profiling using a solution hybridization method and miRNA sequencing.

Aggrecan Mutations in Nonfamilial Short Stature and Short Stature Without Accelerated Skeletal Maturation.

Aggrecan, a proteoglycan, is an important component of cartilage extracellular matrix, including that of the growth plate. Heterozygous mutations in , the gene encoding aggrecan, cause autosomal dominant short stature, accelerated skeletal maturation, and joint disease. The inheritance pattern and the presence of bone age equal to or greater than chronological age have been consistent features, serving as diagnostic clues.

Midkine and pleiotrophin concentrations in needle biopsies of breast and lung masses.

Background/objective: Midkine (MDK) and pleiotrophin (PTN) are two closely related heparin-binding growth factors which are overexpressed in a wide variety of human cancers. We hypothesized that the concentrations of these factors in washout of biopsy needles would be higher in breast and lung cancer than in benign lesions.

Methods: Seventy subjects underwent pre-operative core needle biopsies of 78 breast masses (16 malignancies).

Combined pituitary hormone deficiency in a girl with 48, XXXX and Rathke's cleft cyst.

Background: Tetrasomy X is a rare chromosomal aneuploidy seen in girls, associated with facial dysmorphism, premature ovarian insufficiency and intellectual disability. A Rathke's cleft cyst (RCC) is a remnant of Rathke's pouch which may cause multiple pituitary hormone deficiencies by exerting pressure on the pituitary gland in the sella.

Methods/results: The patient was diagnosed with tetrasomy X by karyotyping during infancy.

Genetics of Short Stature.

Short stature is a common and heterogeneous condition that is often genetic in etiology. For most children with genetic short stature, the specific molecular causes remain unknown; but with advances in exome/genome sequencing and bioinformatics approaches, new genetic causes of growth disorders have been identified, contributing to the understanding of the underlying molecular mechanisms of longitudinal bone growth and growth failure. Identifying new genetic causes of growth disorders has the potential to improve diagnosis, prognostic accuracy, and individualized management, and help avoid unnecessary testing for endocrine and other disorders.

New Genetic Diagnoses of Short Stature Provide Insights into Local Regulation of Childhood Growth .

Idiopathic short stature is a common condition with a heterogeneous etiology. Advances in genetic methods, including genome sequencing techniques and bioinformatics approaches, have emerged as important tools to identify the genetic defects in families with monogenic short stature. These findings have contributed to the understanding of growth regulation and indicate that growth plate chondrogenesis, and therefore linear growth, is governed by a large number of genes important for different signaling pathways and cellular functions, including genetic defects in hormonal regulation, paracrine signaling, cartilage matrix, and fundamental cellular processes.

EZH1 and EZH2 promote skeletal growth by repressing inhibitors of chondrocyte proliferation and hypertrophy.

Histone methyltransferases EZH1 and EZH2 catalyse the trimethylation of histone H3 at lysine 27 (H3K27), which serves as an epigenetic signal for chromatin condensation and transcriptional repression. Genome-wide associated studies have implicated EZH2 in the control of height and mutations in EZH2 cause Weaver syndrome, which includes skeletal overgrowth. Here we show that the combined loss of Ezh1 and Ezh2 in chondrocytes severely impairs skeletal growth in mice.

Midkine and Pleiotrophin Concentrations in Amniotic Fluid in Healthy and Complicated Pregnancies.

Background: Midkine (MDK) and pleiotrophin (PTN) are heparin-binding growth factors that, in rodents, are highly expressed in early life and decrease to undetectable levels by adulthood. The potential roles of MDK and PTN in human growth and development are not completely elucidated.

Method And Findings: To delineate the role of MDK and PTN in human development, we developed high sensitivity assays to measure their concentrations in amniotic fluid (AF) at various gestational ages in both healthy and complicated pregnancies.