scholarly journals Disorders of sex development: timing of diagnosis and management in a single large tertiary center

2018 ◽  
Vol 7 (4) ◽  
pp. 595-603 ◽  
Author(s):  
E Kohva ◽  
P J Miettinen ◽  
S Taskinen ◽  
M Hero ◽  
A Tarkkanen ◽  
...  
Keyword(s):  
Turner Syndrome ◽  
Klinefelter Syndrome ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Disorders Of Sex Development ◽  
Survey Period ◽  
Temporal Shift ◽  
Diagnosis And Management ◽  
Bilateral Cryptorchidism ◽  
Tertiary Center

Background We describe the phenotypic spectrum and timing of diagnosis and management in a large series of patients with disorders of sexual development (DSD) treated in a single pediatric tertiary center. Methods DSD patients who had visited our tertiary center during the survey period (between 2004 and 2014) were identified based on an ICD-10 inquiry, and their phenotypic and molecular genetic findings were recorded from patient charts. Results Among the 550 DSD patients, 53.3% had 46,XY DSD; 37.1% had sex chromosome DSD and 9.6% had 46,XX DSD. The most common diagnoses were Turner syndrome (19.8%, diagnosed at the mean age of 4.7 ± 5.5 years), Klinefelter syndrome (14.5%, 6.8 ± 6.2 years) and bilateral cryptorchidism (23.1%). Very few patients with 46,XY DSD (7%) or 46,XX DSD (21%) had molecular genetic diagnosis. The yearly rate of DSD diagnoses remained stable over the survey period. After the release of the Nordic consensus on the management of undescended testes, the age at surgery for bilateral cryptorchidism declined significantly (P < 0.001). Conclusions Our results show that (i) Turner syndrome and Klinefelter syndrome, the most frequent single DSD diagnoses, are still diagnosed relatively late; (ii) a temporal shift was observed in the management of bilateral cryptorchidism, which may favorably influence patients’ adulthood semen quality and (iii) next-generation sequencing methods are not fully employed in the diagnostics of DSD patients.

scholarly journals The laboratory in the multidisciplinary diagnosis of differences or disorders of sex development (DSD)

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Maria Luisa Granada ◽  
Laura Audí
Keyword(s):  
Multidisciplinary Team ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Disorders Of Sex Development ◽  
Gonadal Development ◽  
Abnormal Development ◽  
Sex Characteristics ◽  
Fetal Life ◽  
Sex Development ◽  
Male Sex

Abstract Objectives The development of female or male sex characteristics occurs during fetal life, when the genetic, gonadal, and internal and external genital sex is determined (female or male). Any discordance among sex determination and differentiation stages results in differences/disorders of sex development (DSD), which are classified based on the sex chromosomes found on the karyotype. Content This chapter addresses the physiological mechanisms that determine the development of female or male sex characteristics during fetal life, provides a general classification of DSD, and offers guidance for clinical, biochemical, and genetic diagnosis, which must be established by a multidisciplinary team. Biochemical studies should include general biochemistry, steroid and peptide hormone testing either at baseline or by stimulation testing. The genetic study should start with the determination of the karyotype, followed by a molecular study of the 46,XX or 46,XY karyotypes for the identification of candidate genes. Summary 46,XX DSD include an abnormal gonadal development (dysgenesis, ovotestes, or testes), an androgen excess (the most frequent) of fetal, fetoplacental, or maternal origin and an abnormal development of the internal genitalia. Biochemical and genetic markers are specific for each group. Outlook Diagnosis of DSD requires the involvement of a multidisciplinary team coordinated by a clinician, including a service of biochemistry, clinical, and molecular genetic testing, radiology and imaging, and a service of pathological anatomy.

scholarly journals GENETICS IN ENDOCRINOLOGY: Approaches to molecular genetic diagnosis in the management of differences/disorders of sex development (DSD): position paper of EU COST Action BM 1303 ‘DSDnet’

2018 ◽  
Vol 179 (4) ◽  
pp. R197-R206 ◽  
Author(s):  
L Audí ◽  
S F Ahmed ◽  
N Krone ◽  
M Cools ◽  
K McElreavey ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Best Practice ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Disorders Of Sex Development ◽  
Initial Step ◽  
Copy Number Variations ◽  
Position Paper ◽  
Sex Development ◽  
Complementary Approach

The differential diagnosis of differences or disorders of sex development (DSD) belongs to the most complex fields in medicine. It requires a multidisciplinary team conducting a synoptic and complementary approach consisting of thorough clinical, hormonal and genetic workups. This position paper of EU COST (European Cooperation in Science and Technology) Action BM1303 ‘DSDnet’ was written by leading experts in the field and focuses on current best practice in genetic diagnosis in DSD patients. Ascertainment of the karyotpye defines one of the three major diagnostic DSD subclasses and is therefore the mandatory initial step. Subsequently, further analyses comprise molecular studies of monogenic DSD causes or analysis of copy number variations (CNV) or both. Panels of candidate genes provide rapid and reliable results. Whole exome and genome sequencing (WES and WGS) represent valuable methodological developments that are currently in the transition from basic science to clinical routine service in the field of DSD. However, in addition to covering known DSD candidate genes, WES and WGS help to identify novel genetic causes for DSD. Diagnostic interpretation must be performed with utmost caution and needs careful scientific validation in each DSD case.

Does Timing of Diagnosis and Management of Iatrogenic Ureter Injuries Affect Outcomes? Experience From a Tertiary Center

Urology ◽  
2020 ◽  
Author(s):  
Hal D Kominsky ◽  
Nayan C Shah ◽  
Nicholas J Beecroft ◽  
Dinah Diab ◽  
Iryna M Crescenze ◽  
...  
Keyword(s):  
Diagnosis And Management ◽  
Tertiary Center

Diagnosis and Management of Cardiomyopathies – A Focus on Genetics, Cardiac Magnetic Resonance and Clinical Features

2011 ◽  
Vol 7 (3) ◽  
pp. 225
Author(s):  
Gianfranco Sinagra ◽  
Michele Moretti ◽  
Giancarlo Vitrella ◽  
Marco Merlo ◽  
Rossana Bussani ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Cardiac Magnetic Resonance ◽  
Magnetic Resonance ◽  
Imaging Techniques ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Routine Clinical Practice ◽  
Clinical Approach ◽  
Diagnosis And Management ◽  
Made In

In recent years, outstanding progress has been made in the diagnosis and treatment of cardiomyopathies. Genetics is emerging as a primary point in the diagnosis and management of these diseases. However, molecular genetic analyses are not yet included in routine clinical practice, mainly because of their elevated costs and execution time. A patient-based and patient-oriented clinical approach, coupled with new imaging techniques such as cardiac magnetic resonance, can be of great help in selecting patients for molecular genetic analysis and is crucial for a better characterisation of these diseases. This article will specifically address clinical, magnetic resonance and genetic aspects of the diagnosis and management of cardiomyopathies.

Atypical Clinical Presentation of Persistent Müllerian Duct Syndrome in Siblings

2021 ◽  
pp. 1-6
Author(s):  
Evgenia Globa ◽  
Nataliya Zelinska ◽  
Nina Siryk ◽  
Anu Bashamboo ◽  
Kenneth McElreavey
Keyword(s):  
Genetic Diagnosis ◽  
Autosomal Recessive Disorder ◽  
Normal Male ◽  
Compound Heterozygous ◽  
Mullerian Duct ◽  
Müllerian Duct ◽  
Persistent Müllerian Duct Syndrome ◽  
Persistent Mullerian Duct Syndrome ◽  
Bilateral Cryptorchidism ◽  
Duct Syndrome

Persistent Müllerian duct syndrome (PMDS) is a rare autosomal recessive disorder characterized by the lack of regression of the derivatives of the Müllerian ducts in males. Boys with this condition usually present with unilateral or bilateral cryptorchidism, inguinal hernias, and reproductive disorders with normal male genitalia. Variants in the AMH or AMHR2 genes are responsible for the development of this syndrome. The genetic diagnosis and surgery in PMDS is challenging for both the endocrinologist and the urologist. Here, we describe the management of 2 siblings from 1 family who presented with bilateral cryptorchidism and hypospadias at birth. One child had testis located in the pelvis in the position of normal ovaries, while the other child had testis which were located in the inguinal canals (bilateral inguinal cryptorchidism). Exome sequencing revealed a compound heterozygous variant in the AMHR2 gene c.1388G>A, p.R463H and c.1412G>A p.R471H. To our knowledge, hypospadias has not been described in association with PMDS.

Clinical and genetic investigation of 136 Japanese patients with congenital hypothyroidism

2020 ◽  
Vol 33 (6) ◽  
pp. 691-701 ◽  
Author(s):  
Tatsushi Tanaka ◽  
Kohei Aoyama ◽  
Atsushi Suzuki ◽  
Shinji Saitoh ◽  
Haruo Mizuno
Keyword(s):  
Congenital Hypothyroidism ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Japanese Patients ◽  
Thyroid Stimulating Hormone ◽  
Allelic Variant ◽  
Genetic Investigation ◽  
Pathogenic Variants ◽  
Recessive Genes ◽  
Molecular Genetic Diagnosis

AbstractObjectivesCongenital hypothyroidism (CH) is the most common congenital endocrine disorder. Recent advances in genetic testing have revealed its causative mutations in some CH patients. However, the underlying etiology remains unknown in most patients. This study aimed to perform clinical and genetic investigation in Japanese CH patients to uncover genotype-phenotype correlations.MethodsWe enrolled 136 Japanese patients with transient or permanent CH between April 2015 and March 2017, and performed next-generation sequencing of 19 genes implicated in CH.ResultsWe identified potentially pathogenic bi-allelic variants in DUOX2, TSHR, and TPO in 19, 5, and 1 patient, respectively (autosomal recessive), and a potentially pathogenic mono-allelic variant in NKX2-1 (autosomal dominant) in 1 patient. Molecular genetic diagnosis was highly suggested in 26 patients (19%) from 23 families. We also detected a potentially pathogenic mono-allelic variant in five recessive genes (DUOX2, TSHR, TG, DUOXA2, and TPO) in 31 unrelated patients (23%), although the pathogenicity of these variants remains inconclusive. Patients with bi-allelic DUOX2 variants showed a more severe clinical presentation in infancy than those with bi-allelic TSHR variants. However, this trend reversed beyond infancy. There were no statistical differences in initial thyroid stimulating hormone, free thyroxine, thyroglobulin, and levothyroxine dose as of March 2017 between patients with bi-allelic and mono-allelic DUOX2 variants.ConclusionsThe prevalence of potentially-pathogenic variants in Japanese CH patients was similar to that found by previous reports. Our study demonstrates a genotype-phenotype correlation in Japanese CH patients.

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