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Urologia Internationalis 2022Mixed gonadal dysgenesis is the most common chromosomal abnormality with ambiguous genitalia, defined as a 45,X/46,XY mosaicism. It can present with a normal male...
Mixed gonadal dysgenesis is the most common chromosomal abnormality with ambiguous genitalia, defined as a 45,X/46,XY mosaicism. It can present with a normal male phenotype, ambiguous genitalia, or features of Turner syndrome. A 14-year-old patient was referred to the genetics clinic due to hypospadia, cryptorchidism, and aortic coarctation. During the physical examination, short stature, webbed neck, and Blashko lines on his back were noted. He had a previous karyotype reported as normal. However, due to an inadequate evolution and a low resolution on the previous test, a higher resolution karyotype was performed, identifying a mosaicism 45,X/46,XY. A multidisciplinary board examined the case, and follow-up with tumor markers was carried out to evaluate the presence of gonadoblastoma, one of the main complications in these patients. Treatment should be transdisciplinary and focused on the particular characteristics of each case. Other treatment alternatives include corrective surgery and hormonal therapy.
Topics: Disorders of Sex Development; Female; Gonadal Dysgenesis, Mixed; Humans; Male; Mosaicism; Phenotype; Turner Syndrome
PubMed: 34929697
DOI: 10.1159/000519368 -
Frontiers in Endocrinology 2021Despite different genetic background, Noonan syndrome (NS) shares similar phenotype features to Turner syndrome (TS) such as short stature, webbed neck and congenital... (Comparative Study)
Comparative Study
BACKGROUND
Despite different genetic background, Noonan syndrome (NS) shares similar phenotype features to Turner syndrome (TS) such as short stature, webbed neck and congenital heart defects. TS is an entity with decreased growth hormone (GH) responsiveness. Whether this is found in NS is debated.
METHODS
Data were retrieved from combined intervention studies including 25 children diagnosed with NS, 40 diagnosed with TS, and 45 control children (all prepubertal). NS-children and TS-girls were rhGH treated after investigation of the GH/IGFI-axis. GH was measured with poly- and monoclonal antibodies; 24hGH-profile pattern analysed by PULSAR. The NS-children were randomly assigned to Norditropin 33 or 66 μg/kg/day, and TS-girls were consecutively treated with Genotropin 33 or 66 μg/kg/day.
RESULTS
Higher PULSAR-estimates of 24h-profiles were found in both NS-children and TS-girls compared to controls: Polyclonal GH24h-profile (Mean ± SD) was higher in both groups (44 ± 23mU/L, p<0.01 in NS; 51 ± 47, p<0.001 in TS; compared to 30 ± 23 mU/L in controls) as was GH-baseline (1.4 ± 0.6 mU/L in NS; 2.4 ± 2.4 mU/L in TS, p<0.01 for both, compared to 1.1 ± 1.2 mU/L in controls). Pre-treatment IGFI was 2.2 lower in NS-children (-1.7 ± 1.3) compared to TS-girls (0.6 ± 1.8, p<0.0001). GH, IGFI/IGFBP3-ratio, and chronological age at start of GH accounted for 59% of the variance in first-year growth response in NS.
CONCLUSION
Both prepubertal NS-children and TS-girls had a high GH secretion, but low IGFI/IGFBP3 levels only in NS-children. Both groups presented a broad individual response. NS-children showed higher response in IGFI and growth, pointing to higher responsiveness to GH treatment than TS-girls.
Topics: Body Height; Child; Female; Human Growth Hormone; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Male; Noonan Syndrome; Phenotype; Turner Syndrome
PubMed: 34858328
DOI: 10.3389/fendo.2021.737893 -
Journal of Cardiovascular Development... Oct 2021Turner syndrome is a rare disorder resulting from complete or partial loss of the second sex chromosome. Common manifestations include delayed growth, premature ovarian... (Review)
Review
Turner syndrome is a rare disorder resulting from complete or partial loss of the second sex chromosome. Common manifestations include delayed growth, premature ovarian failure, congenital heart defects, endocrine disorders, lymphedema, and webbed neck. People with Turner syndrome have significantly increased mortality risk primarily due to cardiovascular abnormalities. The mechanisms that lead to these defects are not completely understood and are obscured by the significant variability of both karyotype and phenotype without consistent correlation between the two. This paper presents a review of the recent literature surrounding the symptoms, mechanisms, diagnosis, and treatment of Turner syndrome with a focus on cardiovascular manifestations. With technological advancements in genetics, the molecular processes of Turner syndrome have begun to be dissected. Certain genes on the X chromosome that typically escape inactivation have been implicated in both specific manifestations and broader risk categories. Recently identified genome-wide epigenetic changes may help explain the variability in presentation. It remains unclear as to how the combination of these factors results in the overall clinical picture, but advances in genomic, genetic, epigenetic, and -omics technology hold promise for providing insights that will improve the medical management of individuals with Turner syndrome.
PubMed: 34821691
DOI: 10.3390/jcdd8110138 -
Archives of Endocrinology and Metabolism Nov 2021To investigate the presence of chromosome mosaicism, especially for the presence of Y derived material in 45,X women with Turner syndrome (TS).
OBJECTIVE
To investigate the presence of chromosome mosaicism, especially for the presence of Y derived material in 45,X women with Turner syndrome (TS).
METHODS
FISH and PCR were performed for the presence of chromosome mosaicism and Y-derived-material and genetic findings were correlated to clinical data.
RESULTS
Thirty-one participants were enrolled: 18 (58%) had chromosome mosaicisms (FISH), Y-derived material was found in 2. Yet, SRY primer was found with PCR in only one of them and DYZ3 was not found. The most frequent clinical findings were short or webbed neck (81,82%), high-arched palate (78%), breast hypertelorism, e cubitus valgus and genu valgus (57.6%, both), short fourth metacarpals (46.9%), epicanthic folds (43.8%), shield chest (43.8%), lymphedema (37.5%), and low set ears (34.4%). Both patients with Y-derived-material had primary amenorrhea, dyslipidemia and reached the height of 150 cm despite not treated with recombinant growth hormone (GHr). One of them showed 26% of leukocytes with Y-derived material and few clinical findings.
CONCLUSION
FISH techniques proved efficient in detecting chromosome mosaicisms and Y-derived material and searching in different tissues such as mouth cells is critical due to the possibility of tissue-specific mosaicism. Phenotypical variance in TS may be a signal of chromosome mosaicisms, especially with the presence of Y-derived material.
Topics: Body Height; Chromosomes; Female; Humans; Mosaicism; Polymerase Chain Reaction; Turner Syndrome
PubMed: 34762780
DOI: 10.20945/2359-3997000000403 -
Forensic Science, Medicine, and... Mar 2022An 89-year-old man involved in a vehicle crash was found at autopsy to have a linear seat belt mark on the right side of his neck associated with extensive injuries of...
An 89-year-old man involved in a vehicle crash was found at autopsy to have a linear seat belt mark on the right side of his neck associated with extensive injuries of the right paraspinal muscles with fracture-dislocation and separation of cervical vertebrae 5 and 6. There was also fracture of the right facet joint between cervical vertebrae 5 and 6 and laceration of the right vertebral artery. Death was due to a cervical seat belt injury with spinal fracture and laceration of the right vertebral artery. The presence of extensive injuries to the right paraspinal muscles and cervical vertebra 5-6 fact joint beneath the seat belt mark would be in keeping with trauma due to the belt webbing, rather than mere hyperextension/flexion of the cervical spine. This report demonstrates a rare form of seat belt injury, transection of the vertebral artery, and suggests that the finding of seat belt markings on the lateral aspect of the neck should prompt examination for this type of lethal vascular injury at autopsy.
Topics: Accidents, Traffic; Aged, 80 and over; Humans; Lacerations; Male; Seat Belts; Spinal Fractures; Vertebral Artery
PubMed: 34655043
DOI: 10.1007/s12024-021-00429-2 -
Zhonghua Er Ke Za Zhi = Chinese Journal... Sep 2021To explore the clinical characteristics and mutation spectrum of ALPK3-related pediatric cardiomyopathy and craniofacial-skeletal abnormalities in children. The... (Review)
Review
To explore the clinical characteristics and mutation spectrum of ALPK3-related pediatric cardiomyopathy and craniofacial-skeletal abnormalities in children. The clinical data during a follow-up of 11 years including clinical features, echocardiogram, electrocardiogram, cardiac magnetic resonance, genetic testing, and other data of a child firstly diagnosed with ALPK3 gene-related cardiomyopathy and craniofacial-skeletal abnormalities in China were collected retrospectively. The literatures containing the keyword of "ALPK3 gene" published in the China National Knowledge Infrastructure, Wanfang database and PubMed were collected up to November 2020. Then, the clinical features and gene mutations of ALPK3 gene-related pediatric cardiomyopathy with craniofacial-skeletal features were summarized. A female patient aged 10 months who presented with an enlarged heart for 2 months, was admitted to the hospital and initially diagnosed with endocardial elastic fibrosis. The echocardiography showed features of dilated left ventricle (LV) and LV systolic dysfunction. Low-set ears, webbed neck, a grade 2/6 systolic murmur at lower left sternal area and bilateral absent flexion creases of dig were observed. After treatment, the size and function of the heart recovered to normal at age 13 months. However, the ventricular septum and LV wall were thicker than normal values. Then, the diagnosis was revised to hypertrophic cardiomyopathy(HCM) and suspected congenital malformation syndrome. LV hypertrophy (LVH) progressed slowly before the age of 8 years and then progressed rapidly. At age 9 years, compound heterozygous ALPK3 mutations (c.721dup, p.Y241Lfs*42(exon 1) and c.4840C>T, p.R1614*(exon 10)) were detected in the proband and the mutations had not been reported previously. Then, the final diagnosis of ALPK3 gene-related pediatric cardiomyopathy with craniofacial-skeletal features was made. During the follow up of 11 years, regular follow-up echocardiographic images showed progressive LVH. At age 11 years, electrocardiogram showed LVH, ST-T changes in multiple-lead, T wave inversion, and prolonged QT intervals. Cardiac magnetic resonance showed biventricular hypertrophy and late gadolinium enhancement showed non-uniform enhancement of left and right ventricular myocardium. A total of 7 articles published in English were retrieved, and no Chinese literature was found. Twenty-eight cases were reported in the articles plus the patient in this study. Twenty-four mutations were reported worldwide, 18 patients carried homozygous mutations and 10 patients compound heterozygous mutations. Eleven patients showed dilated cardiomyopathy (DCM) at early stage of disease, and 10 of them transitioned to HCM at the disease progression stage. Eight patients presented with HCM at early stage of disease. Nine patients initially exhibited a mixed phenotype of DCM and HCM, and 6 of them eventually progressed to HCM. Electrocardiogram showed prolonged QT interval. Extracardiac features included short stature, special face, cleft palate, webbed neck, joint contracture, and scoliosis, etc. Progressive myocardial hypertrophy is a major feature of ALPK3 gene-related cardiomyopathy with craniofacial-skeletal malformations. Precise diagnosis depends on molecular genetic techniques. More cases should be accumulated for further analysis on the genotype-phenotype correlation and prognosis assessment.
Topics: Cardiomyopathies; Cardiomyopathy, Hypertrophic; Child; Contrast Media; Female; Gadolinium; Humans; Infant; Retrospective Studies
PubMed: 34645221
DOI: 10.3760/cma.j.cn112140-20210222-00150 -
Journal of the American Association of... Oct 2021The spectrum of Turner syndrome (TS) includes Turner syndrome mosaicism (TSM), which is typically a nonhereditary chromosomal abnormality. Turner syndrome mosaicism...
The spectrum of Turner syndrome (TS) includes Turner syndrome mosaicism (TSM), which is typically a nonhereditary chromosomal abnormality. Turner syndrome mosaicism presents uncommonly to primary care providers (PCPs), who often fail to recognize the subtle signs. The average age at diagnosis for common TS and TSM karyotype is 5.4 years, averaging 7.3 years. Often genetic confirmation, management, and recommended surveillance are delayed. Oftentimes, the PCP suspects a genetic etiology of an unusual phenotype, such as pinna placement or other unusual ear configurations, webbed neck with low posterior hairline, wide-spaced nipples, or short stature among other presentations. The PCP or geneticist orders diagnostic studies to confirm the diagnosis, such as a karyotype. After diagnosis, the PCP refers to the geneticist who initiates surveillance and makes recommendations for management. There are potential neurocognitive, cardiovascular, renal, reproductive, and endocrine issues. Treatment literature is vague and parental concerns are linked to quality mental health and quality of life for the family member with TS or TSM. The purpose of this article was to use a case study to introduce the topic of TS and TSM and to assist the PCP in the identification and management of patient and family concerns.
Topics: Humans; Karyotyping; Mosaicism; Primary Health Care; Quality of Life; Turner Syndrome
PubMed: 34628444
DOI: 10.1097/JXX.0000000000000643 -
Cureus Jul 2021Turner syndrome (TS), or Bonnevie-Ullrich syndrome, also known as congenital ovarian hypoplasia syndrome, is the most common sex chromosome abnormality in females in...
Turner syndrome (TS), or Bonnevie-Ullrich syndrome, also known as congenital ovarian hypoplasia syndrome, is the most common sex chromosome abnormality in females in approximately 1 in 2000 live birth. It occurs when the X chromosome is partially or completely missing in females caused by monosomy or structural abnormalities of the X chromosome. It is mainly diagnosed in late childhood or adolescent age and rarely identified during the neonatal period. It is characterized by short stature, webbed neck, lymphedema of extremities, widely spaced-out nipples, and cubital valgus. Early diagnosis of TS allows for appropriate and timely initiation of therapy with comprehensive care. We report a case of a neonate presented with the complaint of edema of feet since birth and syndromic features. TS was diagnosed by the chromosomal analysis, which demonstrated a gene karyotype of 46.X,i(X)(q10){20}.
PubMed: 34513364
DOI: 10.7759/cureus.16733 -
Urology Dec 2021This report describes an adolescent with Mixed Gonadal Dysgenesis and unexpected mosaicism [karyotype 46,X,mar(Y)/ 47,X, mar(Y),+mar(Y)].). Diagnosis with 1 month of age...
This report describes an adolescent with Mixed Gonadal Dysgenesis and unexpected mosaicism [karyotype 46,X,mar(Y)/ 47,X, mar(Y),+mar(Y)].). Diagnosis with 1 month of age due to atypical genitalia. He presented a right streak gonad, which was removed due to the risk for germ cell tumor, and a left testis with epididymis barely connected and without vas deferens. Left testis maintenance was sufficient for him to undergo spontaneous puberty. The patient was non-responsive to growth hormone. Webbed neck was the only dysmorphic feature. To the best of our knowledge, there were no similar cases reported with spontaneous pubertal progress reported in the literature.
Topics: Adolescent; Gonadal Dysgenesis, Mixed; Humans; Karyotyping; Male; Mosaicism; Puberty
PubMed: 34437894
DOI: 10.1016/j.urology.2021.08.018 -
Traffic Injury Prevention 2021Occupant kinematics and biomechanical responses are assessed with and without pretensioning of normally seated and out-of-position front-seat occupants in rear sled...
OBJECTIVE
Occupant kinematics and biomechanical responses are assessed with and without pretensioning of normally seated and out-of-position front-seat occupants in rear sled tests. The results are compared to recent studies.
METHODS
Three series of rear sled tests were conducted at 24 and 40 km/h with a 2001 Ford Taurus. Series I consisted of two sled tests with a lap-shoulder belted 50 Hybrid III in the driver seat. Series II included four sled tests with a lap-shoulder belted 50 Hybrid III in both front seats. Two soft foam blocks were added, one was placed on the chest centerline under the shoulder belt and one on the pelvis under the lap belt providing additional webbing. Series III consisted of 8 runs and 16 ATD tests to assess the effect of pretensioning with out-of-positioned (OOP) occupants. The biomechanical responses were normalized with Injury Assessment Reference Values (IARV) for head, neck and chest.
RESULTS
The ATD kinematics and biomechanical responses were similar in the yielding phase when the occupant was normally seated with and without pretensioning. The rebound displacement was greater with pretensioning in the 40 km/h tests due to the shoulder belt slipping off the shoulder. The hip displacement was similar, irrespective of pretensioning. All biomechanical responses were below IARVs. The highest response was for lower neck extension. The normalized response was at about 32% for the 24 km/h tests, irrespective of pretensioning. It was up to 59% in the 40 km/h tests with pretensioning. With the OOP occupants, there were no differences in the kinematics and biomechanical response with pretensioning.
CONCLUSIONS
Testing of the effect of retractor pretensioning with out-of-position occupants and additional belt webbing in moderate to high-speed rear sled tests shows no effect on occupant kinematics and biomechanical responses. The displacement of the hips in a rear impact depends on the compliance of the seatback and amount of pocketing, the stiffness of the seat frame limiting rearward rotation, and the dynamic friction between the occupant and the seatback.
Topics: Acceleration; Accidents, Traffic; Biomechanical Phenomena; Head; Humans; Manikins; Neck; Thorax
PubMed: 34355979
DOI: 10.1080/15389588.2021.1946523