I-DSD: The First 10 Years.

Background: Research and audit are vital for the management of Differences/Disorders of Sex Development (DSD). Clinical networks have a strong potential to drive these activities with the development of care standards including patient experience data and peer-observation of clinical care provision.

Summary: Following the 2005 Consensus Workshop that stressed the need for the regular collection and sharing of data across geographical boundaries, the current I-DSD registry was initially launched in 2008.

Update on the management of a newborn with a suspected difference of sex development.

Differences or disorders of sex development are a group of heterogeneous conditions, which most commonly present in the newborn period, with the appearance of atypical genitalia on newborn examination. Over recent years, the improvement in our knowledge of these conditions has been accompanied by advances in diagnostic technology and therapeutic options, as well as societal shifts in attitudes and expectations. These factors have placed an even greater emphasis than before on the need for early expert input through a multidisciplinary service that can support the patient and the family; perform and interpret the investigations required to reach a diagnosis; and formulate a management plan that lays down the foundation for optimal long-term outcome.

Comparison of Isohelix™ and Rayon swabbing systems for touch DNA recovery from metal surfaces.

A previous study evaluating two swabbing systems found that DNA was best recovered from sterile metal substrates using an Isohelix™ swab wetted with isopropyl alcohol rather than a Rayon swab with water as the wetting agent. We tested the same swabbing systems on metal (aluminum, brass, and stainless steel) and plastic substrates in a regularly touched environment to simulate the non-deliberate transfer of touch evidence likely seen in a casework scenario, to ascertain the performance of these swabs in an uncontrolled situation. Higher amounts of touch DNA were recovered with Isohelix™ swabs (0.

A Nationwide Study of the Prevalence and Initial Management of Atypical Genitalia in the Newborn in Scotland.

Provision of optimum healthcare for infants with atypical genitalia requires a clear understanding of the occurrence of this condition. The objective of this study was to determine the prevalence of atypical genitalia and its initial management. A prospective, electronic survey of clinicians within managed clinical networks in Scotland was undertaken between 2013 and 2019.

Society for Endocrinology UK Guidance on the initial evaluation of a suspected difference or disorder of sex development (Revised 2021).

It is paramount that any child or adolescent with a suspected difference or disorder of sex development (DSD) is assessed by an experienced clinician with adequate knowledge about the range of conditions associated with DSD and is discussed with the regional DSD service. In most cases, the paediatric endocrinologist within this service acts as the first point of contact but involvement of the regional multidisciplinary service will also ensure prompt access to specialist psychology and nursing care. The underlying pathophysiology of DSD and the process of delineating this should be discussed with the parents and affected young person with all diagnostic tests undertaken in a timely fashion.

Experience of health care at a reference centre as reported by patients and parents of children with rare conditions.

Background: Whilst diagnostic pathways for children with rare conditions have shown marked improvement, concerns remain about the care children with rare conditions receive at the level of the health care provider. There is, therefore, a need to improve our understanding of the health care received and explore the development of benchmarks that can be regularly monitored.

Methods: Patients and parents with rare conditions at a tertiary children's hospital were approached to complete a questionnaire-based survey that enquired on their experience of clinical care.

Parsing the Heterogeneity of Brain Metabolic Disturbances in Autism Spectrum Disorder.

Background: Despite rising prevalence of autism spectrum disorder (ASD), its brain bases remain uncertain. Abnormal levels of N-acetyl compounds, glutamate+glutamine, creatine+phosphocreatine, or choline compounds measured by proton magnetic resonance spectroscopy suggest that neuron or glial density, mitochondrial energetic metabolism, and/or inflammation contribute to ASD neuropathology. The neuroanatomic distribution of these metabolites could help evaluate leading theories of ASD.

Androgen-responsive non-coding small RNAs extend the potential of HCG stimulation to act as a bioassay of androgen sufficiency.

Background: It is unclear whether a short-term change in circulating androgens is associated with changes in the transcriptome of the peripheral blood mononuclear cells (PBMC).

Aims And Methods: To explore the effect of hCG stimulation on the PBMC transcriptome, 12 boys with a median age (range) of 0.7 years (0.

Birth Weight in Different Etiologies of Disorders of Sex Development.

Context: It is well established that boys are heavier than girls at birth. Although the cause of birth weight (BW) difference is unknown, it has been proposed that it could be generated from prenatal androgen action.

Objective: The aim of the current study was to determine the BW of children with disorders of sex development (DSD) of different etiologies and to evaluate the effects of androgen action on BW.

An assessment of the quality of the I-DSD and the I-CAH registries - international registries for rare conditions affecting sex development.

Background: With the proliferation of rare disease registries, there is a need for registries to undergo an assessment of their quality against agreed standards to ensure their long-term sustainability and acceptability.This study was performed to evaluate the I-DSD and I-CAH Registries and identify their strengths and weaknesses.

Methods: The design and operational aspects of the registries were evaluated against published quality indicators.

The Long-Term Outcome of Boys With Partial Androgen Insensitivity Syndrome and a Mutation in the Androgen Receptor Gene.

Background: In boys with suspected partial androgen insensitivity syndrome (PAIS), systematic evidence that supports the long-term prognostic value of identifying a mutation in the androgen receptor gene (AR) is lacking.

Objective: To assess the clinical characteristics and long-term outcomes in young men with suspected PAIS in relation to the results of AR analysis.

Methods: Through the International Disorders of Sex Development Registry, clinical information was gathered on young men suspected of having PAIS (n = 52) who presented before the age of 16 years and had genetic analysis of AR.

The pitfalls associated with urinary steroid metabolite ratios in children undergoing investigations for suspected disorders of steroid synthesis.

Background: Urinary steroid metabolite ratios may improve the diagnostic yield of potential disorders of steroid hormone synthesis.

Objectives: To investigate the range of ratios and their predictive value in children with suspected disorders of steroid synthesis.

Design And Methods: Twelve ratios were calculated on steroid metabolite data analysed by gas chromatography-mass spectrometry in urine samples collected between 2008-2010 from 93 children.

Advances in neuroimaging.

Over the last 20 years there have been great advances in the field of neuroimaging. However, information is still lacking for patients with a disorder of sex development (DSD) due to the rarity of these conditions. In this chapter the authors will review newly emerging techniques with a focus on the connectivity of the brain, describe sexually dimorphic brain structures and functions, and summarise what is known about the neuroanatomy and neurochemistry of individuals with a DSD.

Changes over time in sex assignment for disorders of sex development.

Background And Objective: It is unclear whether the proportion of infants with a disorder of sex development who are raised as male or female has changed over time. The temporal trends in sex assignment of affected cases entered in the International Disorder of Sex Development (I-DSD) Registry were studied.

Methods: Cases of disorders of sex development reported as partial androgen insensitivity syndrome (PAIS; n = 118), disorder of gonadal development (DGD; n = 232), and disorder of androgen synthesis (DAS; n = 104) were divided into those who were born before 1990, 1990-1999, and after 1999.

Novel associations in disorders of sex development: findings from the I-DSD Registry.

Context: The focus of care in disorders of sex development (DSD) is often directed to issues related to sex and gender development. In addition, the molecular etiology remains unclear in the majority of cases.

Objective: To report the range of associated conditions identified in the international DSD (I-DSD) Registry.

Rationalized assessment of prolonged jaundice is safe and cost-effective.

Prolonged jaundice (PJ) in healthy term neonates is common and frequently benign. It can, however, be the earliest manifestation of underlying liver disease. Its management requires a balanced approach, avoiding over-investigation of well babies while ensuring the early identification of those with pathology.

Factors that influence the decision to perform a karyotype in suspected disorders of sex development: lessons from the Scottish genital anomaly network register.

Background: Although a karyotype represents the first objective evidence of investigating a case of suspected disorder of sex development (DSD), the factors that influence the clinician's decision to initiate investigations are unclear.

Methods: Cases of suspected DSD in Scotland were identified through the Scottish Genital Anomaly Network (SGAN) Register. The timing as well as other factors that influence the decision to perform a karyotype were subsequently studied.

Investigation and initial management of ambiguous genitalia.

Infants rarely present with truly ambiguous genitalia and such children should be evaluated by experts who work within a multidisciplinary team that is dedicated for evaluation and management of children and adults with suspected and confirmed disorders of sex development. The paediatric endocrinologist who is a vital and often the central member of this clinical team not only needs to lead the clinical evaluation of the infant systematically but also needs to be sensitive to the needs of the infant, the parents and the rest of the team. A thorough knowledge of the underlying pathophysiology and the strengths and weaknesses of the investigative tools that are available for reaching a diagnosis is crucial.

The European disorder of sex development registry: a virtual research environment.

Disorders of sex development (DSD) are a rare group of conditions which require further research. Effective research into understanding the aetiology, as well as long-term outcome of these rare conditions, requires multicentre collaboration often across national boundaries. The EU-funded EuroDSD programme (www.

Detection of cytoplasmic CD antigens within normal human peripheral blood leucocytes.

Polymorphonuclear neutrophils (PMNs) are capable of synthesizing various pro-inflammatory cytokines which may indirectly influence specific immune responses. PMNs may also have the capacity to present foreign peptides to helper T cells (Th cells). In support of this hypothesis, recent studies have shown that neutrophils, when activated by the correct combination of cytokines, can be induced to express cell surface major histocompatibility complex (MHC) Class II (DR) antigen, CD80 (B7.