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Pathogenic variants of the SOHLH1 gene are responsible for an autosomal recessive form of ovarian dysgenesis; this gene encodes a transcription factor expressed early in spermatogonia and oocytes and contributes to folliculogenesis. Previously, four affected women from two unrelated families reported homozygous variants in the SOHLH1 gene, but none had a history of gonadal malignancy or a histologic description. We present two sisters and their paternal great-aunt with a history of primary amenorrhea, pubertal delay, and hypergonadotrophism who came from an inbred Mexican family. The proband was the younger sister who was referred for bilateral dysgerminoma. She had a normal blood karyotype, and whole-exome sequencing analysis revealed a novel homozygous missense variant, c.275C>T, in SOHLH1; several family members were also analyzed. In addition to pure dysgerminoma, histopathological analysis revealed an ovarian cortex with fibrosis and almost total absence of follicles. This work confirms the inheritance of ovarian dysgenesis 5, supports the occurrence of cell loss in mouse models, and suggests that affected women should undergo periodic imaging surveillance due to the likely risk of tumor development. [ABSTRACT FROM AUTHOR]

This article discusses a case study of a female patient and her affected niece who have a homozygous frameshift variant of the CLPP gene, which is associated with severe Perrault syndrome. The proband has symptoms including hearing loss, primary ovarian insufficiency, abnormal brain white matter, and developmental delay. The study describes the genetic variant and its predicted effects, as well as the clinical features of the patients. The authors suggest that severe Perrault syndrome may result from biallelic null-alleles of CLPP, while hypomorphic variants may be associated with milder symptoms. The research was supported by various funding sources and the authors declare no conflicts of interest. [Extracted from the article]

Ovarian dysgenesis (OD), an XX disorder of sex development, presents with primary amenorrhea, hypergonadotrophic hypogonadism, and infertility. In an Ashkenazi Jewish patient with OD, whole exome sequencing identified compound heterozygous frameshifts in FIGNL1, a DNA damage response (DDR) gene: c.189del and c.1519_1523del. Chromosomal breakage was significantly increased in patient cells, both spontaneously, and following mitomycin C exposure. Transfection of DYK-tagged FIGNL1 constructs in HEK293 cells showed no detectable protein in FIGNL1c.189del and truncation with reduced expression in FIGNL1c.1519_1523del (64% of wild-type [WT], P = .003). FIGNL1 forms nuclear foci increased by phleomycin treatment (20.6 ± 1.6 vs 14.8 ± 2.4, P = .02). However, mutant constructs showed reduced DYK-FIGNL1 foci formation in non-treated cells (0.8 ± 0.9 and 5.6 ± 1.5 vs 14.8 ± 2.4 in DYK-FIGNL1WT, P < .001) and no increase with phleomycin treatment. In conclusion, FIGNL1 loss of function is a newly characterized OD gene, highlighting the DDR pathway's role in ovarian development and maintenance and suggesting chromosomal breakage as an assessment tool in XX-DSD patients. [ABSTRACT FROM AUTHOR]

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Kallmann syndrome (KS) is an uncommon genetic disorder characterized by isolated congenital hypogonadotropic hypogonadism (CHH) and anosmia/hyposmia. KS originates from abnormal embryonic migration of olfactory axons and gonadotropin-releasing hormone (GnRH)-synthesizing neurons. It can be challenging to diagnose due to its heterogeneous clinical presentation and genes implied. Herein, we report a rare phenotype of KS in two sisters accompanied by a variety of nonreproductive disorders such as hypoparathyroidism, hypercortisolism, atrophy of the cerebellum, intellectual disability, and remarkably, ovarian dysgenesis. Additionally, both subjects present muscle weakness, exercise intolerance, marked hypotonia and seizures, being suspected, although not fully confirmed, mitochondrial encephalomyopathy. These cases illustrate the heterogeneous clinical presentation and the diagnostic difficulties often found in patients suffering from this condition. These clinical features have never been described before as associated with KS; therefore, we decided to report this novel KS phenotype. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Perrault syndrome (PRLTS) is an uncommon hereditary condition distinguished by ovarian failure in females and sensorineural hearing loss. Infertility can be the presenting problem for a serious disease. History and physical examination is very essential among infertile couples., Abstract: Perrault syndrome (PRLTS) is an uncommon hereditary condition distinguished by ovarian failure in females and sensorineural hearing loss. This case presentation describes a 22-year-old female from Saudi Arabia with PRLTS. The patient presented with progressive bilateral hearing loss since childhood, impacting her academic achievement. Additionally, she experienced amenorrhea since the age of 18 years, with previous investigations showing no hormonal imbalances. Other laboratory tests, including bone mineral density, kidney and liver function, electrolytes, and lipid profile, showed mostly normal results, except for a slightly abnormal lipid profile with low high-density lipoprotein and high low-density lipoprotein levels. This case highlights the challenges faced by individuals with PRLTS, specifically progressive hearing loss and gonadal dysfunction, leading to infertility. Further evaluation and management are warranted to address the patient's hearing impairment and fertility concerns, with a multidisciplinary approach involving audiology, endocrinology, and reproductive medicine., Competing Interests: The authors have declared that they don't have any conflict of interest., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Perrault syndrome is a rare disorder characterized by ovarian dysgenesis, bilateral sensorineural hearing loss and associated with mutations in six mitochondrial proteins. Additional neurological features were also described. Herein, we report on a 27‐year‐old woman with Perrault syndrome (PS), moderate ataxia and axonal sensory‐motor peripheral neuropathy in whom we identified compound heterozygous mutations in the TWNK gene (p.Val507Ile and the novel p.Phe248Ser variant). Fewer than 30 patients with PS have been reported worldwide. Neurological involvement is more frequently associated with mutations in TWNK and indicates possible genotype–phenotype correlations. TWNK mutations should be searched in patients with sensory ataxia, early onset bilateral sensorineural hearing loss, and ovarian dysfunction in women. [ABSTRACT FROM AUTHOR]

Bone morphogenetic protein 15 (BMP15) encodes an oocyte factor with a relevant role for folliculogenesis as homodimer or cumulin heterodimer (BMP15‐GDF9). Heterozygous BMP15 variants in the precursor or mature peptide had been associated with primary ovarian insufficiency (POI), but the underlying mechanism remains elusive and a double dose of BMP15 was suggested to be required for adequate ovarian reserve. We uncovered two homozygous BMP15 null variants found in two girls with POI and primary amenorrhea. Both heterozygous mothers reported physiological menopause. We then performed western blot, immunofluorescence, and reporter assays to investigate how previously reported missense variants, p.Y235C and p.R329C, located in the precursor or mature domains of BMP15, may affect protein function. The p.R329C variant demonstrates an impaired colocalization with growth/differentiation factor 9 (GDF9) at confocal images and diminished activation of the SMAD pathways at western blot and reporter assays in COV434 follicular cell line. In conclusion, BMP15 null mutations cause POI only in the homozygous state, thus discarding the possibility that isolated BMP15 haploinsufficiency can cause evident ovarian defects. Alternatively, heterozygous BMP15 missense variants may affect ovarian function by interfering with cumulin activity. Our data definitely support the fundamental role of BMP15 in human ovarian folliculogenesis. [ABSTRACT FROM AUTHOR]

Summary: Objective: The dual diagnosis of hypoplastic uterus in association with ovarian dysgenesis is regularly reported but the pathogenesis of the association is unclear. The uterus, however, may be invisible to all imaging modalities without at least six months of exogenous oestrogen exposure in complete ovarian failure. We assessed all available case reports in this category to estimate whether the apparent association between primary ovarian insufficiency or Turner syndrome and Mullerian agenesis can be largely accounted for by oestrogen deficiency. Design: A literature review of all cases in which an association between ovarian insufficiency or Turner syndrome and hypoplastic uterus has been reported. Patients: PubMed was searched for all case reports associated with relevant key terms. In total, 22 publications with a total of 25 patients were identified and reviewed; 14 subjects had the normal female karyotype (46,XX), and 11 subjects had Turner Syndrome. Measurements: Proportion of subjects who had been exposed to adequate oestrogen prior to the absent uterine diagnosis. Results: A diagnosis of absent uterus was made prior to exposure to exogenous oestrogen in 22/25 (88%) of subjects with primary hypogonadism including 14/14 females with normal karyotype and 8/11 females with Turner syndrome. Conclusions: Oestrogen deficiency is a possible explanation for most subjects being reported as having Mullerian agenesis in association with Turner syndrome or primary ovarian insufficiency. In the presence of oestrogen deficiency, no conclusion can be made about the status of the uterus until adequate exposure to exogenous oestrogen has been completed and we suggest reassessment of the uterus when full adult dose has been reached towards the end of induction of puberty. [ABSTRACT FROM AUTHOR]

Study Question: Can high resolution array-CGH analysis on a cohort of women showing a primary ovarian insufficiency (POI) phenotype in young age identify copy number variants (CNVs) with a deleterious effect on ovarian function?Summary Answer: This approach has proved effective to clarify the role of CNVs in POI pathogenesis and to better unveil both novel candidate genes and pathogenic mechanisms.What Is Known Already: POI describes the progression toward the cessation of ovarian function before the age of 40 years. Genetic causes are highly heterogeneous and despite several genes being associated with ovarian failure, most of genetic basis of POI still needs to be elucidated.Study Design, Size, Duration: The current study included 67 46,XX patients with early onset POI (<19 years) and 134 control females recruited between 2012 and 2016 at the Medical Cytogenetics and Molecular Genetics Lab, IRCCS Istituto Auxologico Italiano.Participants/materials, Setting, Methods: High resolution array-CGH analysis was carried out on POI patients' DNA. Results of patients and female controls were analyzed to search for rare CNVs. All variants were validated and subjected to a gene content analysis and disease gene prioritization based on the present literature to find out new ovary candidate genes. Case-control study with statistical analysis was carried out to validate our approach and evaluate any ovary CNVs/gene enrichment. Characterization of particular CNVs with molecular and functional studies was performed to assess their pathogenic involvement in POI.Main Results and the Role Of Chance: We identified 37 ovary-related CNVs involving 44 genes with a role in ovary in 32 patients. All except one of the selected CNVs were not observed in the control group. Possible involvement of the CNVs in POI pathogenesis was further corroborated by a case-control analysis that showed a significant enrichment of ovary-related CNVs/genes in patients (P = 0.0132; P = 0.0126). Disease gene prioritization identified both previously reported POI genes (e.g. BMP15, DIAPH2, CPEB1, BNC1) and new candidates supported by transcript and functional studies, such as TP63 with a role in oocyte genomic integrity and VLDLR which is involved in steroidogenesis.Large Scale Data: ClinVar database (http://www.ncbi.nlm.nih.gov/clinvar/); accession numbers SCV000787656 to SCV000787743.Limitations, Reasons For Caution: This is a descriptive analysis for almost all of the CNVs identified. Inheritance studies of CNVs in some non-familial sporadic cases was not performed as the parents' DNA samples were not available. Addionally, RT-qPCR analyses were carried out in few cases as RNA samples were not always available and the genes were not expressed in blood.Wider Implications Of the Findings: Our array-CGH screening turned out to be efficient in identifying different CNVs possibly implicated in disease onset, thus supporting the extremely wide genetic heterogeneity of POI. Since almost 50% of cases are negative rare ovary-related CNVs, array-CGH together with next generation sequencing might represent the most suitable approach to obtain a comprehensive genetic characterization of POI patients.Study Funding/competing Interest(s): Supported by Italian Ministry of Health grants 'Ricerca Corrente' (08C203_2012) and 'Ricerca Finalizzata' (GR-2011-02351636, BIOEFFECT) to IRCCS Istituto Auxologico Italiano. [ABSTRACT FROM AUTHOR]

Background: Perrault syndrome is a rare multisystem disorder that manifests with sensorineural hearing loss in both sexes, primary ovarian insufficiency in females and neurological features. The syndrome is heterogeneous both genetically and phenotypically. Case presentation: We reported a consanguineous family (two affected sisters) with Perrault syndrome. The proband had the characteristics of Perrault syndrome: ovarian dysgenesis, bilateral hearing loss and obvious neurological signs. Target genetic sequencing and triplet repeat primed PCR (TP-PCR) plus capillary electrophoresis was conducted to detect causative mutations in the proband. The detected variant was further confirmed in the proband and tested in other family members by Sanger sequencing. Both the proband and her sister were found homozygous for the novel variant HSD17B4 c.298G > T (p.A100S) with their parents heterozygous. Detected by western blot, the protein expression of HSD17B4 mutant was much lower than that of the wild type in SH-SY5Y cells transfected by HSD17B4 wild type or mutant plasmid, which indicated the pathogenicity of the HSD17B4 mutation. Conclusions: Our findings supported that HSD17B4 was one of the genes contributing to Perrault syndrome with the likely pathogenic variant c.298G > T (p.A100S). Special manifestations of cerebellar impairment were found in cases caused by HSD17B4 mutations. Besides, attention should be paid to distinguish Perrault syndrome from D-bifunctional protein deficiency and hereditary ataxia. [ABSTRACT FROM AUTHOR]

Gonadal (ovarian) dysgenesis with normal chromosomes (46, XX), XX female gonadal dysgenesis (XX-GD) is a rare genetically heterogeneous disorder. In 1951, Perrault reported the association of gonadal dysgenesis and deafness, now referred to as Perrault syndrome. Perrault syndrome is a rare autosomal recessive condition affecting both females and males, only females have gonadal dysgenesis associated with sensorineural deafness which is present in both sexes. We present a case of Sporadic Perrault syndrome in a 35-year-old female with primary amenorrhea, sensorineural deafness, marfanoid features, and normal karyotype. There are very few case reports describing the condition, even lesser reports of association with marfanoid habitus. We report this case for its rarity and add to the spectrum of the disease that remains undetermined.

Gonadal (ovarian) dysgenesis with normal chromosomes (46, XX), XX female gonadal dysgenesis (XX-GD) is a rare genetically heterogeneous disorder. In 1951, Perrault reported the association of gonadal dysgenesis and deafness, now referred to as Perrault′s syndrome. Perrault syndrome is a rare autosomal recessive condition affecting both females and males; only females have gonadal dysgenesis associated with sensorineural deafness, which is present in both sexes. We present a case of sporadic Perrault syndrome in a 35-year-old female with primary amenorrhea, sensorineural deafness, marfanoid features and normal karyotype. There are very few case reports describing the condition, even lesser reports of association with marfanoid habitus. We report this case for its rarity and add to the spectrum of the disease that remains undetermined.

Turner syndrome (TS) is tightly associated with hypergonadotropic hypogonadism and ovarian dysgenesis, typically resulting in infertility in the great majority of patients. Therefore females with TS are usually treated with female sex steroids from 11-12years of age until the normal age of natural menopause of around 53-54years of age. Infertility is rated among females with TS as a distressing concern and a detractor from a good quality of life. Options for motherhood for females with TS has expanded during recent years. Originally, only adoption was an option, unless of course for the small minority of TS females that still has ovarian function and are capable of achieving pregnancy through normal means. Oocyte donation has become the mainstream option in many countries and seems to work well, especially if patients have been treated with optimal estrogen and gestagen for a prolonged time before the intervention. It comes with an increased risk of cardiovascular complications and TS oocyte donation pregnancies are viewed as high risk pregnancies necessitating increased vigilance. Oocyte cryopreservation of own oocytes is also becoming an option in a select group of TS and has special challenges. Ovarian tissue cryopreservation is a promising new techniques that has been applied successfully in children with cancer. Currently, several trials are running around the world evaluating this techniques in TS. The genetics and genomics behind the ovarian dysgenesis seen in TS is not understood, but new studies have elucidated global changes in DNA methylation and RNA expression in blood from persons with TS and it is likely that similar changes are present in the ovaries. We still, however, need more thorough research to fully uncover the genetic background of ovarian failure in TS. Gene expression studies and methylation analysis from ovarian TS tissues still needs to be performed., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Abstract: Mutations in POLG account for one of the most frequent nuclear encoded causes of mitochondrial disorders to date. Individuals harboring POLG mutations exhibit fairly heterogeneous clinical presentations leading to increasing difficulties in classifying these patients into defined clinical phenotypes. This study aims to investigate the molecular basis of a mitochondrial cytopathy in a patient with 3-methylglutaconic aciduria and to expand the clinical phenotype associated with POLG mutations. Clinical, molecular and genetic analyses as well as neurophysiological examinations were carried out for a 23-year-old woman of mixed Caucasian and Latin American ancestry with a history of cataracts diagnosed at age 1year, she had onset of distal muscle weakness at age 2years progressing to atrophy and ovarian dysgenesis at puberty. The patient was found to have 3-methylglutaconic acid with normal 3 hydroxyisovaleric acid on urine organic acid analysis. POLG sequencing was done and a heterozygous variant, c.2851T>A (p.Y951N) was found which is predicted to be deleterious. There are limited reports of POLG mutations in individuals with 3-methylglutaconic aciduria. This case report of a young woman with a heterozygous mutation in POLG, presenting with muscle weakness and atrophy at a young age aims to aid clinicians in similar challenging diagnostic situations as well as enhances our understanding of POLG-related disease phenotypes. [Copyright &y& Elsevier]

Thymulin is a thymic hormone exclusively produced by the thymic epithelial cells. After its discovery and initial characterization in the 1970s, it was demonstrated that thymulin production and secretion is strongly influenced by the neuroendocrine system. Conversely, a growing core of information, to be reviewed here, points to thymulin as a hypophysiotropic peptide. Additionally, thymulin was shown to possess anti-inflammatory and analgesic properties in the brain. In recent years, a synthetic DNA sequence coding for a biologically active analog of thymulin, metFTS, was constructed and cloned in different adenoviral vectors. These include bidirectional regulatable Tet-Off vector systems that simultaneously express metFTS and green fluorescent protein and that can be downregulated reversibly by the addition of the antibiotic doxycycline. A number of recent studies suggest that thymulin gene therapy may be a suitable therapeutic strategy to prevent some of the endocrine and reproductive alterations that typically appear in congenitally athymic (nude) mice, taken as a suitable model of neuroendocrine and reproductive aging. The present article briefly reviews the literature on the physiology of the thymulin-pituitary axis as well as on the new molecular tools available to exploit the therapeutic potential of thymulin. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

New thinking has arisen about the origin of adult onset diseases stemming from a collective body of evidence commonly referred to as the developmental origins of health and disease. This conceptual paradigm posits that certain adult onset diseases arise during critical or sensitive windows of human development or even transgenerationally. The testicular dysgenesis hypothesis (TDS) postulates an in utero origin for adverse male reproductive outcomes, and is an excellent example of the early origins of the paradigm. Despite similarities in the development of the male and female reproductive tracks, noticeably absent is a collective body of evidence focusing on the plausibility of an early origin for gynecologic outcomes and later onset of adult diseases. Using the TDS paradigm, we synthesized the available literature relative to the ovarian dysgenesis syndrome (ODS), which we define as alterations in ovarian structure or function that may manifest as fecundity impairments, gynecologic disorders, gravid diseases or later onset adult diseases. We evaluated environmental exposures, particularly the role of endocrine disrupting chemicals, in relation to these outcomes, and found evidence (although fragmented) consistent with an in utero origin of gynecologic outcomes, which in turn is associated with later onset of adult diseases. The findings are interpreted within the ODS paradigm while delineating methodological challenges and future research opportunities designed to answer critical data gaps regarding the origin of fecundity, gravid health and chronic diseases affecting the female population. [ABSTRACT FROM PUBLISHER]

Premature ovarian failure (POF) is unexplained amenorrhoea (>6 months), increased FSH (1.20 IU/L) and LH occurring before 40 years. Several genes are reported as having significance in POF, including genes governing regulation of the hypothalamic-pituitary--ovarian axis, but their role in ovarian physiology is not known. Deletions or translocations in Xq arm have been found to be associated with POF, assuming presence of ovarian-related genes but ovary-related function of these genes is unclear. Several researchers have suggested specific loci on Xq critical region, POF1 and POF2 and genes DIA, FMR1 and FMR2. The understanding of ovarian physiology, its regulation and genes involved is important to explain the causes of POF. Some genes coordinate development of germ cell to primordial stage, e.g. GDF9, BMP15 and NGF, while others regulate development of further stages, such as FSH and LH. Mutation in these genes may lead to female infertility and are likely to be candidate genes for POF. Recently, association between blepharophimosis--ptosis--epicanthus inversus syndrome type 1 and POF has emerged as a possibility. Galactosaemia is also shown to be important in POF due to toxic effects of accumulated galactose or downstream products. Thus, understanding the role of several genes can be used for the appropriate genetic diagnosis, research and in the clinical practice of POF. [ABSTRACT FROM AUTHOR]

Abstract: Premature ovarian failure (POF) is a primary ovarian defect characterized by absent menarche or premature depletion of ovarian follicles before the age of 40 years. However, in several instances the distinction between definitive or intermittent POF may be difficult on clinical bases, therefore the more appropriate term Primary Ovarian Insufficiency (POI) has been recently proposed and will be used in this review. POI is a heterogeneous disorder affecting approximately 1% of women <40 years. The most severe forms present with absent pubertal development and primary amenorrhea, whereas forms with post-pubertal onset are characterized by disappearance of menstrual cycles (secondary amenorrhea) associated with a defective folliculogenesis. POI is generally characterized by low levels of gonadal hormones (estrogens and inhibins) and high levels of gonadotropins (LH and FSH) (hypergonadotropic amenorrhea). Heterogeneity of POI is reflected by the variety of possible causes, including autoimmunity, toxics, drugs, as well as genetic defects. Several data indicate that POI has a strong genetic component. In this manuscript we discuss the X chromosome abnormalities that are associated with POI. [Copyright &y& Elsevier]

Thymulin is a thymic hormone exclusively produced by the thymic epithelial cells. It consists of a nonapeptide component coupled to the ion zinc, which confers biological activity to the molecule. After its discovery in the early 1970s, thymulin was characterized as a thymic hormone involved in several aspects of intrathymic and extrathymic T cell differentiation. Subsequently, it was demonstrated that thymulin production and secretion is strongly influenced by the neuroendocrine system. Conversely, a growing core of information, to be reviewed here, points to thymulin as a hypophysotropic peptide. In recent years, interest has arisen in the potential use of thymulin as a therapeutic agent. Thymulin was shown to possess anti-inflammatory and analgesic properties in the brain. Furthermore, an adenoviral vector harboring a synthetic gene for thymulin, stereotaxically injected in the rat brain, achieved a much longer expression than the adenovirally mediated expression in the brain of other genes, thus suggesting that an anti-inflammatory activity of thymulin prevents the immune system from destroying virus-transduced brain cells. Other studies suggest that thymulin gene therapy may also be a suitable therapeutic strategy to prevent some of the endocrine and metabolic alterations that typically appear in thymus-deficient animal models. The present article briefly reviews the literature on the physiology, molecular biology, and therapeutic potential of thymulin. [ABSTRACT FROM AUTHOR]

Abstract: Stefin A (Stfa) acts as a competitive inhibitor of intracellular papain-like cysteine proteases which play important roles in normal cellular functions such as general protein turnover, antigen processing and ovarian follicular growth and maturation. In the mouse there are at least three different variants of Stfa (Stfa1, Stfa2 and Stfa3). Recent genetic studies identified structural polymorphisms in Stfa1 and Stfa2 as candidates for Aod1b, a locus controlling susceptibility to day three thymectomy (D3Tx)-induced autoimmune ovarian disease (AOD). To evaluate the functional significance of these polymorphisms, recombinant allelic proteins were expressed in Escherichia coli, purified and characterized. The polymorphisms do not markedly alter the folding characteristics of the two proteins. Stfa1 and Stfa2 both act as fast and tight binding inhibitors of endopeptidases papain and cathepsins L and S, however their interaction with exopeptidases cathepsins B, C and H was several orders of magnitude weaker compared to human, porcine and bovine Stfa. Notwithstanding, the K i values for the interactions of Stfa1-b from AOD resistant C57BL/6J mice was 10-fold higher than that of the Stfa1-a allele from susceptible A/J mice for papain, cathepsins B, C and H but not L and S. In contrast, the inhibitory activities of Stfa2-a and Stfa2-b were found to be roughly equivalent for all targets peptidases. [Copyright &y& Elsevier]

Pigmentary type of orthochromatic leukodystrophy (POLD) is an adult-onset leukodystrophy, characterized pathologically by the presence of glial and microglial cytoplasmic pigment inclusions. The complete phenotype, genotype and pathogenetic mechanisms in POLD have not been elucidated. We followed for 18 years a woman with autopsy-proven POLD, who presented with ‘frontal’ dementia and spasticity. Her further course was marked by progressive mutism, apraxia and seizures. Her sister had died of the same disease after a much more rapidly progressing course. These sisters had primary infertility with pathologic evidence of streak ovaries. Diagnosis was confirmed in both cases by post-mortem examination. POLD is a rare cause of adult-onset leukodystrophy presenting with dementia. Ovarian dysgenesis is extremely rare in the absence of demonstrable chromosomal abnormalities and extends the clinical spectrum of POLD. [ABSTRACT FROM AUTHOR]

To better understandfactors contributing to behavioral development, we studied patients with Turner syndrome (TS), a disorder typically marked by prenatal onset of ovarian dysfunction. We compared girls and women (ages 12 and up) with TS (n = 21) to matched controls (n = 21) in cognitive and motor skills, as well as sex-typed personality characteristics and activity preferences. Measures were categorized (based on prior studies) as showing an average male advantage (male-superior measures), female advantage (female-superior measures), or no sex difference (sex-neutral measures). It was hypothesized that, if gonadal function contributes to behavioral development, effects of this deficiency would be more prominent on sexually differentiated than sex-neutral measures and thus that patient–control differences would be most marked for measures that show sex differences. Our findings indicated that TS patients and controls differed more on cognitive and motor domains that show sex differences than on sex-neutral domains. Patients also had more “undifferentiated” personalities and showed reduced sex-typed interests and activities. Differing experiences, as indexed by interests and activities, did not explain the observed cognitive and motor differences. These results are consistent with a role for ovarian hormones acting on the brain to influence cognitive and behavioral development, although they do not rule out other possible interpretations. [Copyright &y& Elsevier]

The bone mineral status of 17 girls with Turner's syndrome was evaluated by single photon absorptiometry. Bone mineral content (BMC) was 25.4% below that predicted by normalization for age, sex, height, weight, and bone width. Only 25% of this demineralization could be attributed to delayed skeletal maturation. Bones of girls who received estrogen replacement therapy were less demineralized than those of the others. The bone mineral deficit became less pronounced with advancing age. It could not be determined if the apparent effect of estrogens was related to age or if the apparent improvement with age was really due to an effect of estrogen treatment. For 8 subjects followed longitudinally there was no significant change in the BMC deficit. [ABSTRACT FROM AUTHOR]

Gonadal (ovarian) dysgenesis with normal chromosomes (46, XX), XX female gonadal dysgenesis (XX-GD) is a rare genetically heterogeneous disorder. In 1951, Perrault reported the association of gonadal dysgenesis and deafness, now referred to as Perrault syndrome. Perrault syndrome is a rare autosomal recessive condition affecting both females and males, only females have gonadal dysgenesis associated with sensorineural deafness which is present in both sexes. We present a case of Sporadic Perrault syndrome in a 35-year-old female with primary amenorrhea, sensorineural deafness, marfanoid features, and normal karyotype. There are very few case reports describing the condition, even lesser reports of association with marfanoid habitus. We report this case for its rarity and add to the spectrum of the disease that remains undetermined. [ABSTRACT FROM AUTHOR]

Gonadal (ovarian) dysgenesis with normal chromosomes (46, XX), XX female gonadal dysgenesis (XX-GD) is a rare genetically heterogeneous disorder. In 1951, Perrault reported the association of gonadal dysgenesis and deafness, now referred to as Perrault's syndrome. Perrault syndrome is a rare autosomal recessive condition affecting both females and males; only females have gonadal dysgenesis associated with sensorineural deafness, which is present in both sexes. We present a case of sporadic Perrault syndrome in a 35-year-old female with primary amenorrhea, sensorineural deafness, marfanoid features and normal karyotype. There are very few case reports describing the condition, even lesser reports of association with marfanoid habitus. We report this case for its rarity and add to the spectrum of the disease that remains undetermined. [ABSTRACT FROM AUTHOR]