Children

2023

Jump to: 2022, 2021

10 pages, 615 KiB

Open AccessArticle

Follistatin Is Associated with Bone Mineral Density in Lean Adolescent Girls with Increased Physical Activity

by Jaak Jürimäe, Liina Remmel, Anna-Liisa Tamm, Priit Purge, Katre Maasalu and Vallo Tillmann

Children 2023, 10(7), 1226; https://doi.org/10.3390/children10071226 - 14 Jul 2023

Viewed by 1197

Abstract

Follistatin is a member of the activin–follistatin–inhibin hormonal system and is proposed to affect bone metabolism. However, data regarding the effect of follistatin on bone are relatively scarce and contradictory in humans. The purpose of the current study was to investigate possible associations [...] Read more.

Follistatin is a member of the activin–follistatin–inhibin hormonal system and is proposed to affect bone metabolism. However, data regarding the effect of follistatin on bone are relatively scarce and contradictory in humans. The purpose of the current study was to investigate possible associations of serum follistatin concentration with bone mineral characteristics in lean and physically active adolescent girls. Bone mineral density, body composition, resting energy expenditure and different energy homeostasis hormones in serum including follistatin, leptin and insulin were investigated. Significant relationships (p < 0.05) between serum follistatin (1275.1 ± 263.1 pg/mL) and whole-body (WB) bone mineral content (r = 0.33), WB areal bone mineral density (aBMD) (r = 0.23) and lumbar spine (LS) aBMD (r = 0.29) values were observed. Serum follistatin remained associated with LS aBMD independent of body fat and lean masses (r = 0.21; p < 0.05). However, the follistatin concentration explained only 3% (R² × 100; p = 0.049) of the total variance in LS aBMD values. In conclusion, serum follistatin concentrations were associated with bone mineral values in lean adolescent girls with increased physical activity. Follistatin was an independent predictor of lumbar spine areal bone mineral density, which predominantly consists of trabecular bone. Full article

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8 pages, 601 KiB

Open AccessCase Report

A Novel Variant in the TP53 Gene Causing Li–Fraumeni Syndrome

by Dimitrios T. Papadimitriou, Constantine A. Stratakis, Antonis Kattamis, Stavros Glentis, Constantine Dimitrakakis, George P. Spyridis, Panagiotis Christopoulos, George Mastorakos, Nikolaos F. Vlahos and Nicoletta Iacovidou

Children 2023, 10(7), 1150; https://doi.org/10.3390/children10071150 - 30 Jun 2023

Cited by 2 | Viewed by 1969

Abstract

Li–Fraumeni syndrome (LFS) is an autosomal dominant hereditary cancer syndrome associated with germline pathogenic variants in the tumor protein p53 (TP53) gene and elevated risk of a broad range of early-onset malignancies. Patients with LFS are at risk of a second [...] Read more.

Li–Fraumeni syndrome (LFS) is an autosomal dominant hereditary cancer syndrome associated with germline pathogenic variants in the tumor protein p53 (TP53) gene and elevated risk of a broad range of early-onset malignancies. Patients with LFS are at risk of a second and third primary tumor. A 15-month-old girl consulted for clitoromegaly and pubic hair. Adrenal ultrasound detected a large left adrenal tumor. Left total adrenalectomy confirmed adrenocortical carcinoma. Family history revealed multiple highly malignant neoplasms at an early age across five generations, and a genetic dominant trait seemed probable. Whole-genome sequencing was performed. Multiple members of the family were found positive for a novel likely pathogenic variant (c. 892delGinsTTT, p. Glu298PhefsX48, NM_000546.6) in the TP53 gene, causing the loss of normal protein function through non-sense-mediated mRNA decay. According to the PSV1 supporting criteria and the Auto PVS1 online tool this frameshift variant: hg19/17-7577045-TC-TAAA:NM_000546.6 has a very strong, definitive clinical validity for LFS with autosomal dominant inheritance. Proper guidance resulted in timely diagnosis of a second tumor (primary osteosarcoma) in the index case and in the early detection of breast and cervical cancer in her young mother. Patients with cancer predisposition syndromes like LFS require close multidisciplinary cancer surveillance and appropriate referral to expert centers. Full article

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14 pages, 1049 KiB

Open AccessReview

Investigating the Link between Early Life and Breast Anomalies

by Panagiotis Christopoulos, Alkis Matsas, Makarios Eleftheriades, Georgia Kotsira, Anna Eleftheriades and Nikolaos F. Vlahos

Children 2023, 10(3), 601; https://doi.org/10.3390/children10030601 - 21 Mar 2023

Cited by 3 | Viewed by 1682

Abstract

Several factors during childhood and adolescence are thought to be associated with the development of proliferative benign breast diseases and breast cancer in adulthood. In order to identify them, the authors conducted an extensive review of the literature up to October 2022, searching [...] Read more.

Several factors during childhood and adolescence are thought to be associated with the development of proliferative benign breast diseases and breast cancer in adulthood. In order to identify them, the authors conducted an extensive review of the literature up to October 2022, searching for clinical studies, reports, and guidelines in English. A thorough Medline/Pubmed and Google scholar database research was performed, investigating the link between diet, exercise, age of menarche, body mass index, ionizing radiation exposure during childhood and adolescence, and proliferative breast diseases and breast cancer in adulthood. A list of keywords, including breast disorders, adolescence, childhood, and breast cancer was included in our search algorithm. Numerous studies concede that the development of breast disease in adulthood is influenced by various risk factors, whose influence begins during early childhood and adolescence. Full article

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2022

Jump to: 2023, 2021

11 pages, 1848 KiB

Open AccessCase Report

Identification of the Rare Ala871Glu Mutation in the Androgen Receptor Gene Leading to Complete Androgen Insensitivity Syndrome in an Adolescent Girl with Primary Amenorrhea

by Aikaterini Kapama, Dimitrios T. Papadimitriou, George Mastorakos, Nikolaos F. Vlahos and Maria Papagianni

Children 2022, 9(12), 1900; https://doi.org/10.3390/children9121900 - 3 Dec 2022

Cited by 1 | Viewed by 4209

Abstract

Complete Androgen Insensitivity Syndrome (CAIS) is a rare genetic condition by mutations in the androgen receptor (AR) gene resulting in target issue resistance to androgens and a female phenotype in genetically male individuals. A 16-year-old phenotypically female individual presented to our clinic with [...] Read more.

Complete Androgen Insensitivity Syndrome (CAIS) is a rare genetic condition by mutations in the androgen receptor (AR) gene resulting in target issue resistance to androgens and a female phenotype in genetically male individuals. A 16-year-old phenotypically female individual presented to our clinic with primary amenorrhea. Her clinical evaluation showed normal female external genitalia, Tanner III breast development and sparse pubic and axillary hair (Tanner stage II). Hormonal assessment revealed increased concentrations of Luteinizing Hormone (LH), Testosterone and Antimüllerian Hormone (AMH). Image studies detected no uterus or gonads, but a blind vagina and the karyotype was 46, XY. These findings suggested the diagnosis of CAIS, and genetic testing of the AR gene revealed a rare pathogenic mutation of cytosine to adenine (c.2612C>A) replacing alanine with glutamic acid at position 871 (p.Ala871Glu) in the AR, previously described once in two adult sisters. The patient underwent gonadectomy and received hormonal replacement therapy. This study expands the AR mutation database and shows the complexity and the importance of prompt diagnosis, proper management, and follow-up for CAIS patients, underlining the need for standardized protocols. Full article

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12 pages, 313 KiB

Open AccessEditor’s ChoiceReview

Ovarian Tissue Cryopreservation in Children and Adolescents

by Angeliki Arapaki, Panagiotis Christopoulos, Emmanouil Kalampokas, Olga Triantafyllidou, Alkis Matsas and Nikolaos F. Vlahos

Children 2022, 9(8), 1256; https://doi.org/10.3390/children9081256 - 19 Aug 2022

Cited by 19 | Viewed by 3939

Abstract

Cancer during childhood and adolescence remains a major public health issue, affecting a significant portion of this age group. Although newer anti-cancer treatments have improved survival rates, this comes at a cost in terms of gonadotoxic effects. As a result, the preservation of [...] Read more.

Cancer during childhood and adolescence remains a major public health issue, affecting a significant portion of this age group. Although newer anti-cancer treatments have improved survival rates, this comes at a cost in terms of gonadotoxic effects. As a result, the preservation of fertility is important. Ovarian tissue cryopreservation, one of the newest methods, has some advantages, especially for prepubertal patients: no need for ovarian stimulation, thus, no further risk for estrogen-sensitive cancer types, and preservation of more and better-quality primordial follicles of the ovarian cortex. The most frequent indications include treatment with alkylating agents, ovarian-focused radiotherapy, leukemias, lymphomas, brain and neurological tumors, as well as Turner syndrome and benign hemoglobinopathies. An expected survival exceeding 5 years, the absence of systematic disease and an overall risk of premature ovarian insufficiency over 50% are among the criteria that need to be fulfilled in order for a patient to undertake this method. Orthotopic transplantation is more frequently used, since it can allow both live birth and the recovery of endocrine function. Reimplantation of malignant cells is always a major risk and should always be taken into consideration. Histological analysis, as well as immunohistochemical and molecular methods, are needed in order to improve the search for malignant cells before transplantation. Ovarian tissue cryopreservation appears to be a method with specific benefits, indications and risks which can be an important tool in terms of preserving fertility in younger women. Full article

16 pages, 1184 KiB

Open AccessSystematic Review

Identification of Genetic Causes in Mayer-Rokitansky-Küster-Hauser (MRKH) Syndrome: A Systematic Review of the Literature

by Varvara Ermioni Triantafyllidi, Despoina Mavrogianni, Andreas Kalampalikis, Michael Litos, Stella Roidi and Lina Michala

Children 2022, 9(7), 961; https://doi.org/10.3390/children9070961 - 27 Jun 2022

Cited by 13 | Viewed by 5058

Abstract

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a congenital condition characterizing females with absence of the uterus and part of the vagina. Several genetic defects have been correlated with the presence of MRKH; however, the exact etiology is still unknown due to the complexity of the [...] Read more.

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a congenital condition characterizing females with absence of the uterus and part of the vagina. Several genetic defects have been correlated with the presence of MRKH; however, the exact etiology is still unknown due to the complexity of the genetic pathways implicated during the embryogenetic development of the Müllerian ducts. A systematic review (SR) of the literature was conducted to investigate the genetic causes associated with MRKH syndrome and Congenital Uterine Anomalies (CUAs). This study aimed to identify the most affected chromosomal areas and genes along with their associated clinical features in order to aid clinicians in distinguishing and identifying the possible genetic cause in each patient offering better genetic counseling. We identified 76 studies describing multiple genetic defects potentially contributing to the pathogenetic mechanism of MRKH syndrome. The most reported chromosomal regions and the possible genes implicated were: 1q21.1 (RBM8A gene), 1p31-1p35 (WNT4 gene), 7p15.3 (HOXA gene), 16p11 (TBX6 gene), 17q12 (LHX1 and HNF1B genes), 22q11.21, and Xp22. Although the etiology of MRKH syndrome is complex, associated clinical features can aid in the identification of a specific genetic defect. Full article

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10 pages, 599 KiB

Open AccessArticle

A Mixed-Longitudinal Study of Height Velocity of Greek Schoolchildren and the Milestones of the Adolescent Growth Spurt

by Kleanthis Kleanthous, Dimitrios T. Papadimitriou, Alexandros Gryparis, Vassiliki Papaevangelou and Anastasios Papadimitriou

Children 2022, 9(6), 790; https://doi.org/10.3390/children9060790 - 27 May 2022

Cited by 3 | Viewed by 5541

Abstract

Height velocity (HV) growth charts constructed from longitudinal studies are scarce as they have inherent difficulties, e.g., time, and costs. These difficulties can be partly overcome by a mixed-longitudinal study that covers the entire age range within 3–6 years. To construct HV charts [...] Read more.

Height velocity (HV) growth charts constructed from longitudinal studies are scarce as they have inherent difficulties, e.g., time, and costs. These difficulties can be partly overcome by a mixed-longitudinal study that covers the entire age range within 3–6 years. To construct HV charts of Greek children and to estimate the milestones of the adolescent growth spurt (AGS), i.e., the onset of AGS (take-off), peak HV, and total pubertal growth (TPG), we performed a mixed longitudinal study in 1514 Greek schoolchildren (6–18 years) with height measurements every 6 months during three schoolyears. We constructed HV charts for boys and girls. Take-off occurs earlier in girls, and, in both sexes, it precedes by 1–1.5 years the appearance of physical signs of puberty. PHV in boys occurs at 12.61 years and in girls at 10.93 years. At take-off, boys are 5 cm taller than girls and TPG for boys is 35.8 cm and for girls 27.3 cm. We constructed HV charts plotted by age, irrespective of pubertal status, and presented data on the milestones of AGS. Furthermore, we suggest that the gradual increase in IGF-1 and E2 that occurs after 5 to 6 years of age triggers the onset of AGS, which precedes physical signs of puberty. Full article

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10 pages, 277 KiB

Open AccessArticle

Vitamin D and Parathyroid Hormone during Growth Hormone Treatment

by Teodoro Durá-Travé and Fidel Gallinas-Victoriano

Children 2022, 9(5), 725; https://doi.org/10.3390/children9050725 - 15 May 2022

Cited by 3 | Viewed by 1999

Abstract

Background. There is some controversy concerning a potential interaction between vitamin D and PTH and the GH/IGF-1 axis. The goal of this study is to assess vitamin D and PTH status in children with GH deficiency at diagnostic and during treatment with [...] Read more.

Background. There is some controversy concerning a potential interaction between vitamin D and PTH and the GH/IGF-1 axis. The goal of this study is to assess vitamin D and PTH status in children with GH deficiency at diagnostic and during treatment with rhGH. Methods. Longitudinal and descriptive study in 110 patients, aged 3.3–9.1 years, with GH deficiency (GHD group) treated with rhGH. At diagnosis and after 12, 24, 36, and 48 months of treatment, a clinical (height, weight, and bone age) and laboratory (phosphorus, calcium, calcidiol, PTH, IGF-1) evaluation was performed. Concurrently, 377 healthy children, aged 3.8–9.7 years, were enrolled and constituted a control group. Vitamin D status was stated in accordance to the U.S. Endocrine Society criteria. Results. No significant differences were found in the prevalence of vitamin D deficiency among control (11.43%) and GHD (13.6%) groups at the moment of diagnosis, remaining without significant changes at 12 (12.9%), 24 (14.6%), 36 (13.1%), and 48 months (13.3%) of treatment. There were not any significant differences in serum levels of calcium, phosphorus, and calcidiol, but a steady increase (p < 0.001) in PTH was detected. Conclusions. Prepubertal patients with GH deficient do not appear to have a higher risk of vitamin D deficiency than healthy subjects, and with treatment with rhGH, no changes in the organic content of vitamin D were observed although a significant increase in PTH levels was detected. Full article

7 pages, 826 KiB

Open AccessCase Report

Early Diagnosis of Pseudohypoparathyroidism before the Development of Hypocalcemia in a Young Infant

by Su Kyeong Hwang, Ye Jee Shim, Seung Hwan Oh and Kyung Mi Jang

Children 2022, 9(5), 723; https://doi.org/10.3390/children9050723 - 15 May 2022

Cited by 1 | Viewed by 2826

Abstract

Pseudohypoparathyroidism (PHP) is a rare, heterogeneous disorder characterized by end-organ resistance to parathyroid hormone (PTH). PTH resistance causes elevated PTH levels, hypocalcemia, and hyperphosphatemia. Since hypocalcemia causes life-threatening events, early diagnosis is crucial. However, the diagnosis of PHP is elusive during infancy because [...] Read more.

Pseudohypoparathyroidism (PHP) is a rare, heterogeneous disorder characterized by end-organ resistance to parathyroid hormone (PTH). PTH resistance causes elevated PTH levels, hypocalcemia, and hyperphosphatemia. Since hypocalcemia causes life-threatening events, early diagnosis is crucial. However, the diagnosis of PHP is elusive during infancy because PHP is usually diagnosed with hypocalcemia-induced symptoms, which develop later in childhood when calcium requirements increase. A 1-month-old girl was referred to our clinic for elevated thyroid-stimulating hormone (TSH) levels on newborn screening. When measured 1 month after levothyroxine treatment, her TSH level normalized. At 4-months-old, multiple hard nodules were noted on her trunk. A punch skin biopsy revealed osteoma cutis associated with Albright’s hereditary osteodystrophy, a major characteristic of PHP. We performed targeted sanger sequencing of the GNAS gene and detected a heterozygous variant c.150dupA (p.Ser51Ilefs*3) in both the proband and her mother, causing frameshift and premature termination mutations. The patient was diagnosed with PHP Ia when she had normal calcium, phosphorous, and PTH levels. We report the early diagnosis of PHP Ia without hypocalcemia. It emphasizes the importance of meticulous physical examination in patients with congenital hypothyroidism. Full article

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26 pages, 1413 KiB

Open AccessReview

Perimenstrual Asthma in Adolescents: A Shared Condition in Pediatric and Gynecological Endocrinology

by Valeria Calcaterra, Rossella Elena Nappi, Andrea Farolfi, Lara Tiranini, Virginia Rossi, Corrado Regalbuto and Gianvincenzo Zuccotti

Children 2022, 9(2), 233; https://doi.org/10.3390/children9020233 - 10 Feb 2022

Cited by 9 | Viewed by 4391

Abstract

Asthma is a frequent medical condition in adolescence. The worsening of the most common symptoms perimenstrually is defined as perimenstrual asthma (PMA). The cause of PMA remains unclear, but a role for hormonal milieu is plausible. Data on PMA in adolescents are limited, [...] Read more.

Asthma is a frequent medical condition in adolescence. The worsening of the most common symptoms perimenstrually is defined as perimenstrual asthma (PMA). The cause of PMA remains unclear, but a role for hormonal milieu is plausible. Data on PMA in adolescents are limited, and its management is not fully established. We aimed to discuss the PMA phenomenon in young females from pathophysiology to preventive strategies, focusing on the relationship with the hormonal pattern. The fluctuation of estrogens at ovulation and before menstruation and the progesterone secretion during the luteal phase and its subsequent withdrawal seem to be the culprits, because the deterioration of asthma is cyclical during the luteal phase and/or during the first days of the menstrual cycle. Conventional asthma therapies are not always effective for PMA. Preventive strategies may include innovative hormonal contraception. Even a possible beneficial effect of other hormonal treatments, including estrogens, progestogens, and androgens, as well as leukotriene receptor antagonists and explorative approach using microbial-directed therapy, is considered. The underlying mechanisms, through which sex-hormone fluctuations influence asthma symptoms, represent a challenge in the clinical management of such a distressing condition. Further studies focused on young females are mandatory to promote adolescent health. Full article

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18 pages, 581 KiB

Open AccessArticle

Adipokines Profile and Inflammation Biomarkers in Prepubertal Population with Obesity and Healthy Metabolic State

by Lidia Cobos-Palacios, Mónica Muñoz-Úbeda, Cristina Gallardo-Escribano, María Isabel Ruiz-Moreno, Alberto Vilches-Pérez, Antonio Vargas-Candela, Isabel Leiva-Gea, Francisco J. Tinahones, Ricardo Gómez-Huelgas and María Rosa Bernal-López

Children 2022, 9(1), 42; https://doi.org/10.3390/children9010042 - 2 Jan 2022

Cited by 6 | Viewed by 2694

Abstract

(1) Background and aims: Obesity and high body max index (BMI) have been linked to elevated levels of inflammation serum markers such as C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), adiponectin, and resistin. It has been described that adipose tissue [...] Read more.

(1) Background and aims: Obesity and high body max index (BMI) have been linked to elevated levels of inflammation serum markers such as C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), adiponectin, and resistin. It has been described that adipose tissue presents a high production and secretion of these diverse pro-inflammatory molecules, which may have local effects on the physiology of the fat cell and also systemic effects on other organs. Our aim was to evaluate the impact that lifestyle modifications, following a Mediterranean Diet (MedDiet) program and physical activity (PA) training, would have on inflammatory biomarkers in a metabolically healthy prepubertal population with obesity (MHOPp) from Malaga (Andalusia, Spain). (2) Methods: 144 MHOPp subjects (aged 5–9 years) were included in this study as they met ≤1 of the following criteria: waist circumference and blood pressure ≥ 90 percentile, triglycerides > 90 mg/dL, high-density lipoprotein cholesterol (HDL-c) < 40 mg/dL, or impaired fasting glucose (≥100 md/dL). Selected subjects followed a personalized intensive lifestyle modification. Anthropometric measurements, inflammation biomarkers, and adipokine profile were analyzed after 12 and 24 months of intervention. (3) Results: 144 MHOPp participants (75 boys—52% and 69 girls—48%; p = 0.62), who were 7.8 ± 1.4 years old and had a BMI 24.6 ± 3.3 kg/m², were included in the study. After 24 months of MedDiet and daily PA, a significant decrease in body weight (−0.5 ± 0.2 SD units; p < 0.0001) and BMI (−0.7 ± 0.2 SD units; p < 0.0001) was observed in the total population with respect to baseline. Serum inflammatory biomarkers (IL-6, TNF-alpha, and CRP) after 24 months of intervention were significantly reduced. Adipokine profile (adiponectin and resistin) did not improve with the intervention, as adiponectin levels significantly decreased and resistin levels increased in all the population. Inflammatory biomarkers and adipokine profile had a significant correlation with anthropometric parameters, body composition, and physical activity. (4) Conclusions: After 24 months of lifestyle modification, our MHOPp reduced their Z-score of BMI, leading to an improvement of inflammatory biomarkers but inducing deterioration in the adipokine profile, which does not improve with MedDiet and physical activity intervention. An adequate education within the family about healthier habits is necessary to prevent and reduce an excessive increase in obesity in childhood. Full article

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2021

Jump to: 2023, 2022

12 pages, 1860 KiB

Open AccessArticle

The Assessment of Brain Volume Differences in Idiopathic Central Precocious Puberty Girls; Comparison of Age-Matched Girls and Normal Puberty Girls

by Shin-Eui Park, Ji-Ye Ahn and Eun-Young Kim

Children 2021, 8(9), 797; https://doi.org/10.3390/children8090797 - 11 Sep 2021

Cited by 1 | Viewed by 2474

Abstract

Objective: Although there have been several studies on the neuroanatomical changes in idiopathic central precocious puberty (ICPP), the association between each brain region and ICPP has not yet been clearly elucidated. This study aimed to evaluate the difference in brain structure in ICPP [...] Read more.

Objective: Although there have been several studies on the neuroanatomical changes in idiopathic central precocious puberty (ICPP), the association between each brain region and ICPP has not yet been clearly elucidated. This study aimed to evaluate the difference in brain structure in ICPP compared with age-matched healthy controls and normal puberty controls, and additionally the correlation between brain volume difference and the luteinizing hormone (LH). Materials and Methods: The study enrolled fifteen girls with ICPP, as well as 15 age-matched healthy girls and 15 normal puberty girls as controls. The subjects underwent a 1.5 Tesla Avanto MR Scanner. Anatomical T1-weighted images were acquired with a T1 spin-echo sequence. The volumes of total and regional brain were compared with each of the two control groups and analyzed through the paired T-test, and the brain region related to the peak LH level was also analyzed through a simple correlation test. Results: The mean age of the ICPP group, age-matched group, and puberty group were 8.0 ± 0.9 years, 7.8 ± 0.9 years, and 11.9 ± 0.9 years, respectively. In our findings, the regional cerebral volumes in ICPP were different from age-matched controls. Compared with controls, ICPP showed a significant increase in gray matter (GM) volumes (the medial prefrontal cortex, superior parietal gyrus, supramarginal gyrus, angular gyrus, postcentral gyrus, superior occipital gyrus, cuneus, hippocampus, parahippocampal gyrus, posterior cingulate gyrus (PCgG), cerebellar cortex (Cb)) and in white matter (WM) volumes (the insular, caudate, splenium of corpus callosum (p < 0.001)). Especially, the GM volumes of the PCgG (r = 0.57, p = 0.03) and Cb (r = 0.53, p = 0.04) were correlated positively with LH concentrations stimulated by the gonadotropin-releasing hormone agonist. Compared to the normal puberty control, no significant difference in GM volume was found. Conclusions: This study showed the overall brain volumetric differences between ICPP girls and age-matched controls using voxel-based morphometric analysis, and further showed the correlation between brain volume and the sex hormone in ICPP. Through a comparison between the two groups, the cerebral development pattern of ICPP is similar to that of normal puberty, and these local differences in cerebral volume may affect social and congenital changes. These findings will be useful for understanding the neuroanatomical mechanisms on the specific morphological variations associated with ICPP. Full article

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14 pages, 2532 KiB

Open AccessCase Report

Fetal Fractures in an Infant with Maternal Ehlers-Danlos Syndrome, CCDC134 Pathogenic Mutation and a Negative Genetic Test for Osteogenesis Imperfecta

by Michael F. Holick, Arash Shirvani and Nipith Charoenngam

Children 2021, 8(6), 512; https://doi.org/10.3390/children8060512 - 17 Jun 2021

Cited by 15 | Viewed by 8907

Abstract

Intrauterine fractures are a rare clinical finding caused by abnormal early-life osteogenesis. In this case report, we reported a male infant with twenty-three intrauterine/fetal fractures resembling osteogenesis imperfecta and tested negative for COL1A1 and COL1A2 mutations. The infant’s mother had Ehlers–Danlos syndrome, hypermobility [...] Read more.

Intrauterine fractures are a rare clinical finding caused by abnormal early-life osteogenesis. In this case report, we reported a male infant with twenty-three intrauterine/fetal fractures resembling osteogenesis imperfecta and tested negative for COL1A1 and COL1A2 mutations. The infant’s mother had Ehlers–Danlos syndrome, hypermobility type. Whole-genome sequencing revealed that there were no pathologic mutations previously documented to be associated with intrauterine fracture. Genetic mutations reported to be associated with fragility fractures were identified. These include the pathogenic homozygous mutation in the CCDC134 gene. Other genetic variants that might be responsible for variable expressivity of the skeletal manifestation include the homozygous variants of the genes CCDC134, COL15A1 and ZFPM1, and the heterozygous variants of the genes MYH3, BCHE, AUTS2. This is the first reported case of in utero fractures, that was confirmed by X-ray after birth, in an infant who had no genetic evidence for osteogenesis imperfecta, had a homozygous pathogenic mutation of an osteogenesis gene and whose mother had Ehlers-Danlos syndrome hypermobility type. Therefore, we have identified a new genetic cause for in utero fractures. If after birth, this infant were found to have these fractures in various stages of healing with a negative genetic test for osteogenesis imperfecta he would have been misdiagnosed as due to nonaccidental trauma. Full article

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8 pages, 486 KiB

Open AccessReview

The Effect of Thyrotropin-Releasing Hormone and Antithyroid Drugs on Fetal Thyroid Function

by Nikolaos Vrachnis, Orestis Tsonis, Dionisios Vrachnis, Nikolaos Antonakopoulos, George Paltoglou, Stavroula Barbounaki, George Mastorakos, Minas Paschopoulos and Zoi Iliodromiti

Children 2021, 8(6), 454; https://doi.org/10.3390/children8060454 - 28 May 2021

Cited by 1 | Viewed by 5830

Abstract

A euthyroid pregnant woman will normally have a fetus that displays normal fetal development. However, studies have long demonstrated the role of T3 (Triiodothyronine), T4 (Thyroxine), and TSH (Thyroid Stimulating Hormone) and their degree of penetrability into the fetal circulation. Maternal thyrotropin-releasing hormone [...] Read more.

A euthyroid pregnant woman will normally have a fetus that displays normal fetal development. However, studies have long demonstrated the role of T3 (Triiodothyronine), T4 (Thyroxine), and TSH (Thyroid Stimulating Hormone) and their degree of penetrability into the fetal circulation. Maternal thyrotropin-releasing hormone (TRH) crosses the placental site and, from mid-gestation onward, is able to promote fetal TSH secretion. Its origin is not only hypothalamic, as was believed until recently. The maternal pancreas, and other extraneural and extrahypothalamic organs, can produce TRH variants, which are transported through the placenta affecting, to a degree, fetal thyroid function. Antithyroid drugs (ATDs) also cross the placenta and, because of their therapeutic actions, can affect fetal thyroid development, leading in some cases to adverse outcomes. Furthermore, there are a number of TRH analogues that share the same properties as the endogenous hormone. Thus, in this narrative review, we highlight the interaction of all the above with fetal growth in uncomplicated pregnancies. Full article

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8 pages, 273 KiB

Open AccessArticle

Thyroid Microcarcinoma in Pediatric Population in Romania

by Andreea-Ioana Stefan, Andra Piciu, Maria Margareta Cosnarovici, Monica Dragomir, Romana Netea-Maier and Doina Piciu

Children 2021, 8(5), 422; https://doi.org/10.3390/children8050422 - 20 May 2021

Cited by 1 | Viewed by 2254

Abstract

Thyroid microcarcinoma in pediatric population in Romania Non-medullary thyroid cancer (TC) is the most common endocrine malignancy, with an increasing incidence in the recent years, due to the increase of the thyroid microcarcinoma. Thyroid microcarcinoma (mTC) is defined, according to WHO criteria, as [...] Read more.

Thyroid microcarcinoma in pediatric population in Romania Non-medullary thyroid cancer (TC) is the most common endocrine malignancy, with an increasing incidence in the recent years, due to the increase of the thyroid microcarcinoma. Thyroid microcarcinoma (mTC) is defined, according to WHO criteria, as ≤1 cm dimension thyroid carcinoma, being a rare disease in children population. In adults, the current guidelines recommend a limited surgical approach. In children, however, there are no specific guidelines for mTC. Due to the scarcity of these tumors, mTC in children have largely been understudied, to our knowledge with only one previous publication reporting on the outcomes of a large historic series of patients with mTC from the USA. In Romania, the incidence of TC is rising, one of the reason may be the effect of Chernobyl nuclear accident in the past and the iodine deficiency. The purpose of this study was to describe the characteristics and outcome of children diagnosed with mTC in Romania diagnosed from 1 January 2000 to 31 December 2018. During the study period we identified 77 cases of differentiated TC (papillary and follicular) and of these 20 cases (19.4%) were mTC. The mTC represented roughly one fifth of our nationwide pediatric population diagnosed in the last 20 years, the majority of cases being recorded in adolescents aged between 15–18 years. Although patients with apparently more unfavorable local phenotype were identified, this was not reflected in the outcome of the patients in terms of remission of the disease and survival. Our study illustrates the heterogeneity of the real-life practice with respect to the pediatric mTC, and underscores the need for carefully designed multicenter international studies, including larger cohorts of patients in order to provide the data required for establishing evidence based uniform protocols. The European Reference Networks (ERN), such as the ERN for Rare Endocrine Diseases (Endo-ERN) provides an ideal platform to initiate such collaborative studies. Full article

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13 pages, 1224 KiB

Open AccessReview

Perinatal Inflammation: Could Partial Blocking of Cell Adhesion Molecule Function Be a Solution?

by Nikolaos Vrachnis, Dimitrios Zygouris, Dionysios Vrachnis, Nikolaos Roussos, Nikolaos Loukas, Nikolaos Antonakopoulos, Georgios Paltoglou, Stavroula Barbounaki, Georgios Valsamakis and Zoi Iliodromiti

Children 2021, 8(5), 380; https://doi.org/10.3390/children8050380 - 12 May 2021

Cited by 1 | Viewed by 2840

Abstract

In spite of the great advances made in recent years in prenatal and perinatal medicine, inflammation can still frequently result in injury to vital organs and often constitutes a major cause of morbidity. It is today well established that in neonates—though vulnerability to [...] Read more.

In spite of the great advances made in recent years in prenatal and perinatal medicine, inflammation can still frequently result in injury to vital organs and often constitutes a major cause of morbidity. It is today well established that in neonates—though vulnerability to infection among neonates is triggered by functional impairments in leukocyte adhesion—the decreased expression of cell adhesion molecules also decreases the inflammatory response. It is also clear that the cell adhesion molecules, namely, the integrins, selectins, and the immunoglobulin (Ig) gene super family, all play a crucial role in the inflammatory cascade. Thus, by consolidating our knowledge concerning the actions of these vital cell adhesion molecules during the prenatal period as well as regarding the genetic deficiencies of these molecules, notably leukocyte adhesion deficiency (LAD) I, II, and III, which can provoke severe clinical symptoms throughout the first year of life, it is anticipated that intervention involving blocking the function of cell adhesion molecules in neonatal leukocytes has the potential to constitute an effective therapeutic approach for inflammation. A promising perspective is the potential use of antibody therapy in preterm and term infants with perinatal inflammation and infection focusing on cases in which LAD is involved, while a further important scientific advance related to this issue could be the combination of small peptides aimed at the inhibition of cellular adhesion. Full article

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