scholarly journals LIM Homeodomain (LIM-HD) Genes and Their Co-Regulators in Developing Reproductive System and Disorders of Sex Development

2021 ◽  
pp. 1-15
Author(s):  
Neha Singh ◽  
Domdatt Singh ◽  
Deepak Modi
Keyword(s):  
Primordial Germ Cell ◽  
Disorders Of Sex Development ◽  
Hormone Deficiency ◽  
Delayed Puberty ◽  
Pituitary Hormone ◽  
Sex Development ◽  
Germ Cell Migration ◽  
Müllerian Agenesis ◽  
And Control ◽  
Lim Homeodomain

LIM homeodomain (LIM-HD) family genes are transcription factors that play crucial roles in a variety of functions during embryonic development. The activities of the LIM-HD proteins are regulated by the co-regulators LIM only (LMO) and LIM domain-binding (LDB). In the mouse genome, there are 13 LIM-HD genes (<i>Lhx1</i>–<i>Lhx9</i>, <i>Isl1</i>–<i>2</i>, <i>Lmx1a</i>–<i>1b</i>), 4 Lmo genes (<i>Lmo1</i>–<i>4</i>), and 2 Ldb genes (<i>Ldb1</i>–<i>2</i>). Amongst these, <i>Lhx1</i> is required for the development of the müllerian duct epithelium and the timing of the primordial germ cell migration. <i>Lhx8</i> is necessary for oocyte differentiation and <i>Lhx9</i> for somatic cell proliferation in the genital ridges and control of testosterone production in the Leydig cells. <i>Lmo4</i> is involved in Sertoli cell differentiation. Mutations in <i>LHX1</i> are associated with müllerian agenesis or Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. <i>LHX9</i> gene variants are reported in cases with disorders of sex development (DSD). Mutations in <i>LHX3</i> and <i>LHX4</i> are reported in patients with combined pituitary hormone deficiency having absent or delayed puberty. A transcript map of the <i>Lhx</i>, <i>Lmo,</i> and <i>Ldb</i> genes reveal that multiple LIM-HD genes and their co-regulators are expressed in a sexually dimorphic pattern in the developing mouse gonads. Unraveling the roles of LIM-HD genes during development will aid in our understanding of the causes of DSD.

scholarly journals Spectrum of external genital anomalies in disorders of Sex Development at Children Hospital & Institute of Child Health, Lahore, Pakistan

2020 ◽  
Vol 37 (1) ◽  
Author(s):  
Sarah Khan ◽  
Raafea Tafweez ◽  
Areiba Haider ◽  
Muhammad Yaqoob
Keyword(s):  
Child Health ◽  
Wide Spectrum ◽  
Disorders Of Sex Development ◽  
Ambiguous Genitalia ◽  
Delayed Puberty ◽  
Female Sex ◽  
Sex Development ◽  
Mode Of Presentation ◽  
Genital Ambiguity ◽  
Male Sex

Objective: To describe the mode of presentation and frequency of external genital anomalies in disorder of sex development (DSD) Methods: This cross-sectional study was conducted at Children Hospital & Institute of Child Health, Lahore from January to December, 2016 on Children with DSD above 10 years of age. A detailed history and physical examination were done. Positive findings were recorded on a predesigned proforma and analyzed by SPSS 21. Karyotyping on blood samples was done to determine their genetic sex. Results: Out of 83 DSD children, 67% (n=56) were assigned a female sex at birth of which 9% (n=5) had ambiguous genitalia. Male sex at birth was given to 33% (n=27) of which 96% (n=26) had genital ambiguity. Mode of presentation other than ambiguous genitalia were delayed puberty, amenorrhea, hirsuitism, gynaecomastia, cyclic hematuria etc. Clitoromegaly was the main finding in 62.5% (n=5) and micropenis in 45% (n=9). Karyotypic sex of 56 female sex of rearing was 46XX 80% (n=45), 45X0 13% (n=7), XXX 2% (n=1) and 46 XY in 5% (n=3). Karyotypic sex of 27 male sex of rearing was 46XY in 78% (n=21), 46XX in 15% (n=4) and 47XXY in 7% (n=2). Conclusion: Disorders of sex development presented with a wide spectrum of external genital anomalies ranging from clitoromegaly in females to micropenis and hypospadias in males. There was also an extreme diversity in mode of presentation of these cases including pubertal delay, amenorrhea in females and gender confusion disorders. doi: https://doi.org/10.12669/pjms.37.1.2991 How to cite this:Khan S, Tafweez R, Haider A, Yaqoob M. Spectrum of external genital anomalies in disorders of Sex Development at Children Hospital & Institute of Child Health, Lahore, Pakistan. Pak J Med Sci. 2021;37(1):244-249. doi: https://doi.org/10.12669/pjms.37.1.2991 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

scholarly journals Quality of life in 70 women with disorders of sex development

2006 ◽  
Vol 155 (6) ◽  
pp. 877-885 ◽  
Author(s):  
Trine H Johannsen ◽  
Caroline P L Ripa ◽  
Erik L Mortensen ◽  
Katharina M Main
Keyword(s):  
Quality Of Life ◽  
Disorders Of Sex Development ◽  
Diagnostic Procedures ◽  
Well Being ◽  
Structured Interview ◽  
Life Assessment ◽  
Hormone Deficiency ◽  
Hopkins Symptom Checklist ◽  
Sex Development

Objective: The aim of this study was to assess the quality of life and psychosocial well-being in women with disorders of sex development (DSD). Design: An open case-control study. Methods: Social and psychiatric information was collected via a structured interview from 70 Danish women diagnosed with DSD, 70 controls matched on sex, age, and school education, and six women with isolated genital malformations. Quality of life and mental distress were assessed by ‘Quality of Life-Assessment of Growth Hormone Deficiency in Adults’ (QoL-AGHDA) and three symptom scales from the ‘Hopkins Symptom Checklist’ (SCL-90-R; i.e. somatization, depression, and anxiety) respectively. For both measures, higher scores reflected poorer outcomes. Results: Present relationships and having children were less frequent in patients than in controls (P = 0.02 and P < 0.001 respectively). Previous suicidal thoughts (P = 0.002) and a higher frequency of psychological/psychiatric counseling for severe problems (P = 0.06) were more frequently reported in patients than in controls. The mean QoL-AGHDA score was significantly higher in patients than in controls (5.5 vs 2.9; P = 0.002), especially for congenital adrenal hyperplasia (CAH) females (P = 0.01) and virilized 46,XX and 46,XY females (P = 0.04). The total SCL score was higher in patients than in controls (mean 23.2 vs 20.0), reaching significance for anxiety (mean 6.3 vs 4.3, P = 0.03) with highest score in CAH (P = 0.01). Conclusion: An impaired quality of life and more affective distress were observed especially in CAH patients and virilized 46,XX and 46,XY females. This may be caused by trauma from distressing diagnostic procedures, the chronic illnesses per se, and psychosocial consequences of the disorders.

scholarly journals Misdiagnosis of Mullerian agenesis in a patient with 46, XX gonadal dysgenesis: a missed opportunity for prevention of osteoporosis

2019 ◽  
Vol 2019 ◽  
Author(s):  
Yotsapon Thewjitcharoen ◽  
Veekij Veerasomboonsin ◽  
Soontaree Nakasatien ◽  
Sirinate Krittiyawong ◽  
Thep Himathongkam
Keyword(s):  
Gonadal Dysgenesis ◽  
Hormone Replacement ◽  
Disorders Of Sex Development ◽  
Primary Amenorrhea ◽  
List Type ◽  
Hormone Substitution ◽  
Mrkh Syndrome ◽  
Sex Development ◽  
Exogenous Estrogen ◽  
Müllerian Agenesis

Summary Primary amenorrhea could be caused by disorders of four parts: disorders of the outflow tract, disorders of the ovary, disorders of the anterior pituitary, and disorders of hypothalamus. Delay in diagnosis and hormone substitution therapy causes secondary osteoporosis. Herein, we report a case of a 23-year-old phenotypical female who presented with primary amenorrhea from 46, XX gonadal dysgenesis but had been misdiagnosed as Mayer–Rokitansky–Kuster–Hauser (MRKH) syndrome or Mullerian agenesis. The coexistence of gonadal dysgenesis and MRKH was suspected after laboratory and imaging investigations. However, the vanishing uterus reappeared after 18 months of hormone replacement therapy. Therefore, hormone profiles and karyotype should be thoroughly investigated to distinguish MRKH syndrome from other disorders of sex development (DSD). Double diagnosis of DSD is extremely rare and periodic evaluation should be reassessed. This case highlights the presence of estrogen deficiency state, the uterus may remain invisible until adequate exposure to exogenous estrogen. Learning points: An early diagnosis of disorders of sex development (DSD) is extremely important in order to promptly begin treatment, provide emotional support to the patient and reduce the risks of associated complications. Hormone profiles and karyotype should be investigated in all cases of the presumptive diagnosis of Mayer–Rokitansky–Kuster–Hauser (MRKH) syndrome or Mullerian agenesis. The association between 46, XX gonadal dysgenesis and Mullerian agenesis has been occasionally reported as a co-incidental event; however, reassessment of the presence of uterus should be done again after administration of exogenous estrogen replacement for at least 6–12 months. A multidisciplinary approach is necessary for patients presenting with DSD to ensure appropriate treatments and follow-up across the lifespan of individuals with DSD.

scholarly journals A nonsense variant in FGFR1: a rare cause of combined pituitary hormone deficiency

2020 ◽  
Vol 33 (12) ◽  
pp. 1613-1615
Author(s):  
İbrahim Mert Erbaş ◽  
Ahu Paketçi ◽  
Sezer Acar ◽  
Leman Damla Kotan ◽  
Korcan Demir ◽  
...  
Keyword(s):  
Hypogonadotropic Hypogonadism ◽  
Growth Factor Receptor ◽  
Hormone Deficiency ◽  
Delayed Puberty ◽  
Pituitary Hormone ◽  
Pituitary Hormone Deficiency ◽  
Combined Pituitary Hormone Deficiency ◽  
Midline Defects ◽  
Relationship Of ◽  
The Relationship

AbstractObjectivesVariants in fibroblast growth factor receptor-1 (FGFR1) may either cause isolated hypogonadotropic hypogonadism (IHH) or Kallmann syndrome (KS). Although the relationship of genes classically involved in IHH with combined pituitary hormone deficiency (CPHD) is well established, variants in FGFR1 have been presented as a rare cause of this phenotype recently.Case presentationHerein, we report an adopted 16-year-old male presented with delayed puberty and micropenis. He had undergone surgery for bilateral undescended testes in childhood. He was normosmic, and the pituitary imaging was normal. However, hypogonadotropic hypogonadism and growth hormone deficiency were detected, associated with a heterozygous nonsense variant (c.1864 C>T, p.R622X) in FGFR1.ConclusionsFGFR1 variants are among the causes of IHH and KS, which are inherited in an autosomal dominant manner and can be associated with midline defects. It should also be kept in mind that CPHD may be associated with FGFR1 variants in a subject with normal olfactory function.

scholarly journals Baseline Inhibin B and Anti-Mullerian Hormone Measurements for Diagnosis of Hypogonadotropic Hypogonadism (HH) in Boys with Delayed Puberty

2010 ◽  
Vol 95 (12) ◽  
pp. 5225-5232 ◽  
Author(s):  
Régis Coutant ◽  
Estelle Biette-Demeneix ◽  
Claire Bouvattier ◽  
Natacha Bouhours-Nouet ◽  
Frédérique Gatelais ◽  
...  
Keyword(s):  
Sertoli Cells ◽  
Early Stage ◽  
Hypogonadotropic Hypogonadism ◽  
Inhibin B ◽  
Hormone Deficiency ◽  
Delayed Puberty ◽  
Pituitary Hormone ◽  
Future Fertility ◽  
Testis Volume ◽  
Stage 1

Context: The diagnosis of isolated hypogonadotropic hypogonadism (IHH) in boys with delayed puberty is challenging, as may be the diagnosis of hypogonadotropic hypogonadism (HH) in boys with combined pituitary hormone deficiency (CPHD). Yet, the therapeutic choices for puberty induction depend on accurate diagnosis and may influence future fertility. Objective: The aim was to assess the utility of baseline inhibin B (INHB) and anti-Mullerian hormone (AMH) measurements to discriminate HH from constitutional delay of puberty (CDP). Both hormones are produced by Sertoli cells upon FSH stimulation. Moreover, prepubertal AMH levels are high as a reflection of Sertoli cell integrity. Patients: We studied 82 boys aged 14 to 18 yr with pubertal delay: 16 had IHH, 15 congenital HH within CPHD, and 51 CDP, as confirmed by follow-up. Subjects were genital stage 1 (testis volume &lt;3 ml; 9 IHH, 7 CPHD, and 23 CDP) or early stage 2 (testis volume, 3–6 ml; 7 IHH, 8 CPHD, and 28 CDP). Results: Age and testis volume were similar in the three groups. Compared with CDP subjects, IHH and CPHD subjects had lower INHB, testosterone, FSH, and LH concentrations (P &lt; 0.05), whereas AMH concentration was lower only in IHH and CPHD subjects with genital stage 1, likely reflecting a smaller pool of Sertoli cells in profound HH. In IHH and CPHD boys with genital stage 1, sensitivity and specificity were 100% for INHB concentration of 35 pg/ml or less. In IHH and CPHD boys with genital stage 2, sensitivities were 86 and 80%, whereas specificities were 92% and 88%, respectively, for an INHB concentration of 65 pg/ml or less. The performance of testosterone, AMH, FSH, and LH measurements was lower. No combination or ratio of hormones performed better than INHB alone. Conclusion: Discrimination of HH from CDP with baseline INHB measurement was excellent in subjects with genital stage 1 and fair in subjects with genital stage 2.

Differences of sex development (DSD)

2020 ◽  
pp. 335-350
Author(s):  
Gary Butler ◽  
Jeremy Kirk
Keyword(s):  
Gonadal Dysgenesis ◽  
Gonad Development ◽  
Disorders Of Sex Development ◽  
Androgen Insensitivity Syndrome ◽  
Trisomy 13 ◽  
Delayed Puberty ◽  
Genetic Syndromes ◽  
Sex Development ◽  
Differences Of Sex Development ◽  
21 Hydroxylase Deficiency

• Embryology: the gonad is initially bipotential. • The testes develop under active control of SRY and other genes. Disorders of sex development (DSDs) are classified according to the karyotype: • 46,XY DSD (incomplete masculinization of a male fetus): ◦ The commonest cause is androgen insensitivity syndrome (AIS): ■ mutations in androgen receptor (AR) gene on X chromosome in complete forms ■ alterations in androgen binding in partial forms. ◦ Abnormalities of testosterone synthesis and conversion, may be: ■ isolated, e.g. 17β‎HSD, 5α‎RD ■ occur in association with defects in steroid biosynthesis, e.g. StAR, 3β‎HSD. • Pure 46,XY gonadal dysgenesis (Swyer syndrome): ◦ phenotype unambiguously female; may present with delayed puberty ◦ Müllerian structures are present but only streak gonads are seen. • Mixed gonadal dysgenesis: ◦ usually asymmetrical, e.g. ovary/streak gonad or ovotestis ◦ karyotype is 45,X/46,XY or 46,XX/46,XY. • Pure 46,XX gonadal dysgenesis: ◦ absent puberty in a phenotypically normal female ◦ intact Müllerian structures but streak ovaries; normal genitalia. • 46,XX DSD (masculinization of a female fetus): ◦ the commonest cause is congenital adrenal hyperplasia, with the vast majority (>90%) due to 21-hydroxylase deficiency (21OHD). • Ovotesticular DSD is rare: ◦ aetiology is unknown, and karyotype usually 46,XX ◦ asymmetrical gonad development; ovary and testis or ovotestis. • DSD may also be part of other genetic syndromes, e.g. Antley–Bixler, Smith–Lemli–Opitz, trisomy 13. • Management requires careful evaluation and counselling, working as part of a multidisciplinary team.

Hypopituitarism in children with cerebral palsy

2016 ◽  
Vol 102 (6) ◽  
pp. 559-561 ◽  
Author(s):  
Suma Uday ◽  
Nick Shaw ◽  
Ruth Krone ◽  
Jeremy Kirk
Keyword(s):  
Cerebral Palsy ◽  
Standard Deviation Score ◽  
Hormone Deficiency ◽  
Delayed Puberty ◽  
Pituitary Hormone ◽  
Posterior Pituitary ◽  
Poor Growth ◽  
Children With Cerebral Palsy ◽  
Mri Scans ◽  
Posterior Pituitary Gland

Poor growth and delayed puberty in children with cerebral palsy is frequently felt to be related to malnutrition. Although growth hormone deficiency is commonly described in these children, multiple pituitary hormone deficiency (MPHD) has not been previously reported. We present a series of four children with cerebral palsy who were born before 29 weeks gestation who were referred to the regional endocrinology service, three for delayed puberty and one for short stature, in whom investigations identified MPHD. All patients had a height well below −2 standard deviation score (2nd centile) at presentation and three who had MRI scans had an ectopic posterior pituitary gland. We therefore recommend that the possibility of MPHD should be considered in all children with cerebral palsy and poor growth or delayed puberty. Early diagnosis and treatment is essential to maximise growth and prevent associated morbidity and mortality.

Problem hypogonadyzmu ze szczególnym uwzględnieniem problemu u dziewcząt

2018 ◽  
Vol 21 (1) ◽  
Author(s):  
Grażyna Jarząbek-Bielecka ◽  
Rafał Czepczyński ◽  
Magdalena Pisarska-Krawczyk ◽  
Witold Kędzia ◽  
Paulina Wojtyła-Buciora
Keyword(s):  
Genetic Testing ◽  
Autoimmune Diseases ◽  
Hormone Deficiency ◽  
Delayed Puberty ◽  
Pituitary Hormone ◽  
Hypergonadotropic Hypogonadism ◽  
Hypogonadotrophic Hypogonadism ◽  
Dysmorphic Features ◽  
Molecular Studies ◽  
Secondary Hypogonadism

Hypogonadism is understood as a gonadal defect; it can occur in all periods of life – in embryos, pre-adolescent and post-adolescent children, as well as after menopause. The initial cause of hypogonadism may lie in a pathology of gonads (primary, gonadal, hypergonadotropic hypogonadism) or of the hypothalamic-pituitary system (secondary hypogonadism, hypogonadotrophic hypogonadism). Hypogonadism should be discussed together with the problem of delayed puberty. In all children with delayed puberty, genetic testing with karyotype evaluation is advisable. It is also necessary to exclude pituitary hormone deficiency, especially in children having undergone radiotherapy and/or chemotherapy; it is also necessary to exclude chronic and autoimmune diseases, with special attention brought to the presence of dysmorphic features or anosmia. Molecular studies are also of importance. Guidelines for management of hypogonadism in girls have been presented.

Neuroimaging Review of Pediatric Endocrinopathies

Neurographics ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 33-58
Author(s):  
F.A. Perez ◽  
D. Werny ◽  
C.L. Roth ◽  
J.N. Wright
Keyword(s):  
Mr Imaging ◽  
Cranial Irradiation ◽  
Hormone Deficiency ◽  
Delayed Puberty ◽  
Genetic Mutations ◽  
Pituitary Hormone ◽  
Imaging Findings ◽  
Inflammatory Conditions ◽  
Clinical Presentations ◽  
Hypothalamic Pituitary Axis

The hypothalamic-pituitary axis regulates many important functions in a child, including growth, puberty, and maintenance of physiologic homeostasis. Dysfunction of the hypothalamic-pituitary axis can produce hormone disturbances that result in various pediatric neuroendocrinopathies, including an isolated growth hormone deficiency, multiple pituitary hormone deficiencies, precocious or delayed puberty, central diabetes insipidus, and elevated pituitary hormone conditions (eg, hyperprolactinemia). Although the hormonal abnormalities in a child with endocrinopathy are typically well characterized with clinical and laboratory evaluations by an endocrinologist, neuroimaging with brain MR imaging can be critical for identifying an underlying etiology to guide prognosis and treatment. Neuroendocrinopathies can be congenital, such as from genetic mutations involved in hypothalamic-pituitary axis development, or acquired, such as with pediatric suprasellar masses, trauma, or inflammatory conditions, or after cranial irradiation. This article reviews the clinical presentations, pathophysiologies, etiologies, and MR imaging findings in children who present with specific types of neuroendocrinopathies.Learning Objective: To review the pathophysiologies, etiologies, and associated neuroimaging findings in the most commonly imaged pediatric neuroendocrinopathies.

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