1,014 results match your criteria Kallmann Syndrome and Idiopathic Hypogonadotropic Hypogonadism


[Clinical and genetic features of Kallmann syndrome: an analysis of 5 cases].

Zhongguo Dang Dai Er Ke Za Zhi 2018 Nov;20(11):925-929

Department of Pediatrics, First Affiliated Hospital of Zhejiang University, Hangzhou 310003, China.

Kallmann syndrome (KS) is a rare pediatric disease with major manifestations of olfactory dysfunction and hypogonadotropic hypogonadism. Five children (4 boys and 1 girl) with KS reported in this article were aged between 6 months and 19 years at the time when they attended the hospital. All the children had the clinical manifestation of hypogonadotropic hypogonadism; in addition, three children had olfactory dysfunction (two were found to have olfactory bulb dysplasia on magnetic resonance imaging), one had cleft lip and palate, and one had micropenis and cryptorchidism with right renal agenesis during infancy. Read More

View Article
November 2018
5 Reads

Prevalence and Associated Phenotypes of PLXNA1 Variants in Normosmic and Anosmic Idiopathic Hypogonadotropic Hypogonadism.

Clin Genet 2018 Nov 22. Epub 2018 Nov 22.

Cukurova University, Faculty of Medicine, Division of Pediatric Endocrinology, Adana, Turkey.

Idiopathic Hypogonadotropic Hypogonadism (IHH) can be divided into two major forms, normosmic IHH and Kallmann syndrome (KS). Genetic mutations are responsible for the majority of IHH. PLXNA1 has recently been implicated in the GnRH neuron migration and the etiology of KS. Read More

View Article
November 2018
3 Reads

Assisted reproductive techniques with congenital hypogonadotropic hypogonadism patients: a systematic review and meta-analysis.

BMC Endocr Disord 2018 Nov 19;18(1):85. Epub 2018 Nov 19.

Key laboratory of Endocrinology, Ministry of Health; Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Wang Fu Jing St, Dongcheng district, Beijing, 100730, China.

Background: After hormonal replacement therapy (HRT) including androgen replacement or sequential therapy of estrogen and progesterone, The combination of human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG) and pulsatile GnRH, is not sufficient to produce sufficient gametes in some patients with Congenital hypogonadotropic hypogonadism (CHH). A Systematic review and meta-analysis was performed to determine that assisted reproductive techniques (ART) can effectively treat different causes of infertility.

Methods: To determine the effect of ART on fertility of CHH patients and investigate whether outcomes are similar to infertility due to other causes, we conducted a systematic review and meta-analysis of retrospective trials. Read More

View Article
November 2018

Eugenic concerns, scientific practices: international relations in the establishment of psychiatric genetics in Germany, Britain, the USA and Scandinavia, c.1910-60.

Authors:
Volker Roelcke

Hist Psychiatry 2018 Nov 1:957154X18808666. Epub 2018 Nov 1.

Giessen University, Germany.

The article describes the emergence of research programmes, institutions and activities of the early protagonists in the field of psychiatric genetics: Ernst Rüdin in Munich, Eliot Slater in London, Franz Kallmann in New York and Erik Essen-Möller in Lund. During the 1930s and well into the Nazi period, the last three had been research fellows at the German Research Institute for Psychiatry in Munich. It is documented that there was a continuous mutual exchange of scientific ideas and practices between these actors, and that in all four contexts there were intrinsic relations between eugenic motivations and genetic research, but with specific national adaptations. Read More

View Article
November 2018

Kallmann syndrome and ichthyosis: a case of contiguous gene deletion syndrome.

Endocrinol Diabetes Metab Case Rep 2017 Sep 28;2017. Epub 2017 Sep 28.

Endocrinology Department, Parc Taulí University Hospital, Sabadell, Barcelona, Spain.

Kallmann syndrome is a genetically heterogeneous form of hypogonadotropic hypogonadism caused by gonadotropin-releasing hormone deficiency and characterized by anosmia or hyposmia due to hypoplasia of the olfactory bulbs; osteoporosis and metabolic syndrome can develop due to longstanding untreated hypogonadism. Kallmann syndrome affects 1 in 10 000 men and 1 in 50 000 women. Defects in 17 genes, including KAL1, have been implicated. Read More

View Article
September 2017
5 Reads

Unilateral renal agenesis as an early marker for genetic screening in Kallmann syndrome.

Hormones (Athens) 2018 Sep 25. Epub 2018 Sep 25.

Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, University of Patras Medical School, Patras, Greece.

View Article
September 2018
7 Reads

Kallmann Syndrome With Micropenis.

Authors:
Chia-Po Fu I-Te Lee

Am J Med Sci 2018 Aug 13;356(2):e23. Epub 2018 Mar 13.

Division of Endocrinology and Metabolism, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Medicine, Chung Shan Medical University, Taichung, Taiwan. Electronic address:

View Article

Targeted Gene Panel Sequencing for Molecular Diagnosis of Kallmann Syndrome and Normosmic Idiopathic Hypogonadotropic Hypogonadism.

Exp Clin Endocrinol Diabetes 2018 Sep 14. Epub 2018 Sep 14.

Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea.

Background: Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) is classified either as Kallmann syndrome (KS) with anosmia or normosmic idiopathic hypogonadotropic hypogonadism (nIHH) and caused by mutations in more than 30 different genes. Recent advances in next-generation sequencing technologies have revolutionized the identification of causative genes by using massively parallel sequencing of multiple samples. This study was performed to establish the genetic etiology of IGD using a targeted gene panel sequencing of 69 known human IGD genes. Read More

View Article
September 2018
1 Read

Fertility induction in hypogonadotropic hypogonadal men.

Clin Endocrinol (Oxf) 2018 Dec 9;89(6):712-718. Epub 2018 Oct 9.

Institute of Genetic Medicine, University of Newcastle-upon-Tyne, Newcastle upon Tyne, UK.

Men with hypogonadotropic hypogonadism (HH) are typically azoospermic, and yet HH is one of the few treatable forms of male infertility. Sperm induction protocols using gonadotrophins aim to replicate the natural endocrine control of spermatogenesis. Previously virilised men with adult-onset HH and normal testicular volume respond well to monotherapy in which human chorionic gonadotrophin (hCG) acts as a long-acting LH-analogue stimulating spermatogenesis. Read More

View Article
December 2018

Gonadotropin-releasing hormone (GnRH) deficiency under treatment: psychological and sexual functioning impacts.

Hormones (Athens) 2018 Sep 30;17(3):383-390. Epub 2018 Aug 30.

Department of Psychiatry, University of Patras Medical School, Patras, Greece.

Objective: GnRH (gonadotropin releasing hormone) is a crucial hormone for sexual development, puberty, and fertility, and its deficiency leads to hypogonadotropic hypogonadism (HH), which causes abnormal secondary sexual development and infertility. The combination of the lack of sense of smell, i.e. Read More

View Article
September 2018
4 Reads

Anosmin1 Shuttles Fgf to Facilitate Its Diffusion, Increase Its Local Concentration, and Induce Sensory Organs.

Dev Cell 2018 09 16;46(6):751-766.e12. Epub 2018 Aug 16.

Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA. Electronic address:

Growth factors induce and pattern sensory organs, but how their distribution is regulated by the extracellular matrix (ECM) is largely unclear. To address this question, we analyzed the diffusion behavior of Fgf10 molecules during sensory organ formation in the zebrafish posterior lateral line primordium. In this tissue, secreted Fgf10 induces organ formation at a distance from its source. Read More

View Article
September 2018
193 Reads

Male and Female Hypogonadism.

Nurs Clin North Am 2018 Sep;53(3):395-405

Healthcare in Adult Populations Division, Duke University School of Nursing, DUMC 3322, 307 Trent Drive, Durham, NC 27710, USA. Electronic address:

Hypogonadism is a clinical syndrome that results in hormone deficiency in men and women. Primary hypogonadism is caused by gonadal (testicular or ovarian) failure. Secondary hypogonadism is the result of a dysfunction within the hypothalamus and/or pituitary. Read More

View Article
September 2018
7 Reads

Mutation profiles and clinical characteristics of Chinese males with isolated hypogonadotropic hypogonadism.

Fertil Steril 2018 Aug;110(3):486-495.e5

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, People's Republic of China; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, People's Republic of China. Electronic address:

Objective: To investigate the mutation profiles and clinical characteristics of Chinese males with isolated hypogonadotropic hypogonadism (IHH) and discover new pathogenic genes that cause IHH.

Design: A gene panel, including 31 known IHH genes and 52 candidate genes, was used to perform semiconductor next-generation sequencing.

Setting: University hospital. Read More

View Article
August 2018
6 Reads

Clinical data and genetic mutation in Kallmann syndrome with CHARGE syndrome: Case report and pedigree analysis.

Medicine (Baltimore) 2018 Jul;97(27):e11284

Department of Pediatric Orthopedics.

Rationale: This study aimed to investigate the genetic mutation characteristics of Kallmann syndrome (KS) with CHARGE syndrome through the clinical features and genetic analysis of a pediatric patient with KS in one pedigree.

Patient Concerns: Developmental disorders with olfactory abnormalities, developmental lag, heart malformations, external genital malformations.

Diagnoses: KS combined with some clinical characteristics of CHARGE syndrome. Read More

View Article
July 2018
7 Reads

Delayed puberty versus hypogonadism: a challenge for the pediatrician.

Ann Pediatr Endocrinol Metab 2018 Jun 20;23(2):57-61. Epub 2018 Jun 20.

Department of Pediatrics, Pediatric and Infectious Diseases Unit, Bambino Gesù Children Hospital IRCCS, Rome, Italy.

Constitutional delay of growth and puberty (CDGP) is the most common cause of delayed puberty (DP), is mainly found in males, and is characterized by short stature and delayed skeletal maturation. A family history of the subject comprising the timing of puberty in the parents and physical examination may provide clues regarding the cause of DP. Delayed onset of puberty is rarely considered a disease in either sex. Read More

View Article
June 2018
14 Reads

Case 2: 3-month-old Boy with Micropenis.

Pediatr Rev 2018 Jul;39(7):363-365

Department of Pediatrics, Section of Diabetes and Endocrinology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX.

View Article

Live cyanobacteria produce photocurrent and hydrogen using both the respiratory and photosynthetic systems.

Nat Commun 2018 06 4;9(1):2168. Epub 2018 Jun 4.

The Nancy & Stephen Grand Technion Energy Program (GTEP), Technion - Israel Institute of Technology, Technion City, 32000, Haifa, Israel.

Oxygenic photosynthetic organisms perform solar energy conversion of water and CO to O and sugar at a broad range of wavelengths and light intensities. These cells also metabolize sugars using a respiratory system that functionally overlaps the photosynthetic apparatus. In this study, we describe the harvesting of photocurrent used for hydrogen production from live cyanobacteria. Read More

View Article
June 2018
5 Reads

Pediatric anosmia: A case series.

Int J Pediatr Otorhinolaryngol 2018 Jul 17;110:135-139. Epub 2018 May 17.

Department of Otolaryngology, University of Colorado School of Medicine, Aurora, CO, United States; Department of Pediatric Otolaryngology, Children's Hospital Colorado, Aurora, CO, United States. Electronic address:

Introduction: Little is known about the etiology of olfactory dysfunction in the pediatric population. The aim of this study is to characterize the etiology and clinical features of anosmia and to explore evaluation options in a pediatric population.

Methods: Olfactory dysfunction was identified at a tertiary pediatric hospital between January 2003 and October 2014 using a text-based and ICD-9 search of the electronic health record system. Read More

View Article
July 2018
3 Reads

[Kallmann syndrome with deafness caused by SOX10 mutation: Advances in research].

Zhonghua Nan Ke Xue 2017 Sep;23(9):838-841

PLA Research Institute of Clinical Laboratory Medicine, Jingling Hospital, Nanjing University School of Medicine / Nanjing General Hospital of Nanjing Military Region, Nanjing, Jiangsu 210002, China.

The transcription factor SOX10, as a major actor in the development of the neural crest, plays a key role in the maintenance of progenitor cell multipotency, lineage specification, and cell differentiation. Abnormalities of neural crest development in humans lead to a number of genetic diseases known as neurocristopathies or neural crest disorders. The mutation of SOX10 can cause Kallmann syndrome (KS), which is a clinically and genetically heterogeneous condition and defined by the association between anosmia and hypogonadotropic hypogonadism due to incomplete migration of neuroendocrine gonadotropin-releasing hormone (GnRH) cells along the olfactory, vomeronasal, and terminal nerves. Read More

View Article
September 2017
4 Reads

Alemtuzumab as rescue therapy in a cohort of 50 relapsing-remitting MS patients with breakthrough disease on fingolimod: a multi-center observational study.

J Neurol 2018 Jul 25;265(7):1521-1527. Epub 2018 Apr 25.

Department of Neurology, University Hospital Erlangen, Friedrich-Alexander-University, Erlangen-Nürnberg, Germany.

Background: Relapsing-remitting multiple sclerosis (RRMS) requires efficient immunomodulatory treatment to reach "no evidence of disease activity" status at best. Alemtuzumab and fingolimod have proved to be efficient options in RRMS with active disease course. Yet, side effects and break-through disease may limit long-time treatment and necessitate switch of medication. Read More

View Article
July 2018
4 Reads

A case of Kallmann syndrome associated with a non-functional pituitary microadenoma.

Endocrinol Diabetes Metab Case Rep 2018 17;2018. Epub 2018 Apr 17.

Departments of Internal Medicine and Endocrinology and Radiology, University Hospital Fattouma Bourguiba Monastir, Monastir, Tunisia.

Kallmann syndrome (KS) is a form of hypogonadotropic hypogonadism in combination with a defect in sense of smell, due to abnormal migration of gonadotropin-releasing hormone-producing neurons. We report a case of a 17-year-old Tunisian male who presented with eunuchoid body proportions, absence of facial, axillary and pubic hair, micropenis and surgically corrected cryptorchidism. Associated findings included anosmia. Read More

View Article
April 2018
13 Reads

De novo SOX10 Nonsense Mutation in a Patient with Kallmann Syndrome, Deafness, Iris Hypopigmentation, and Hyperthyroidism.

Ann Clin Lab Sci 2018 Mar;48(2):248-252

The Endocrinology Department of the Third Xiangya Hospital, Central South University, Changsha, Hunan Province, China

Kallmann syndrome (KS) is a clinically and genetically heterogeneous disorder characterized by hypogonadotropic hypogonadism and olfactory dysfunction. Recently, mutations in SOX10, a well-known causative gene of Waardenburg syndrome (WS), have been identified in a few KS patients with additional developmental defects including hearing loss. However, the understanding of SOX10 mutation associates with KS and other clinical consequences remains fragmentary. Read More

View Article
March 2018
23 Reads

Cranial Pair 0: The Nervus Terminalis.

Anat Rec (Hoboken) 2018 Apr 16. Epub 2018 Apr 16.

Laboratorio de Neuroplasticidad y Neurodegeneración, Facultad de Medicina de Ciudad Real, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha, Ciudad Real 13071, Spain.

Originally discovered in elasmobranchs by Fritsh in 1878, the nervus terminalis has been found in virtually all species, including humans. After more than one-century debate on its nomenclature, it is nowadays recognized as cranial pair zero. The nerve mostly originates in the olfactory placode, although neural crest contribution has been also proposed. Read More

View Article
April 2018
1 Read

Identification of a novel mutation in FGFR1 gene in patients with Kallmann syndrome by high throughput sequencing.

Syst Biol Reprod Med 2018 Jun 15;64(3):202-206. Epub 2018 Apr 15.

b Department of Reproductive Medicine , Xiamen Maternity and Child Care Hospital , Xiamen , Fujian , China.

Kallmann syndrome (KS) is a rare clinical and genetic heterogeneity disease, which is familial or sporadic. KS is known to have three patterns of inheritance: X linked recessive inheritance, autosomal dominant inheritance and rare autosomal recessive inheritance. Here, we report a sibling pedigree with autosomal dominant inheritance of KS, and we identified a novel heterozygous frameshift mutation c. Read More

View Article
June 2018
3 Reads

Haploinsufficiency of SIX3 Abolishes Male Reproductive Behavior Through Disrupted Olfactory Development, and Impairs Female Fertility Through Disrupted GnRH Neuron Migration.

Mol Neurobiol 2018 Nov 27;55(11):8709-8727. Epub 2018 Mar 27.

Department of Reproductive Medicine, Center for Reproductive Science and Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0674, USA.

Mating behavior in males and females is dependent on olfactory cues processed through both the main olfactory epithelium (MOE) and the vomeronasal organ (VNO). Signaling through the MOE is critical for the initiation of male mating behavior, and the loss of MOE signaling severely compromises this comportment. Here, we demonstrate that dosage of the homeodomain gene Six3 affects the degree of development of MOE but not the VNO. Read More

View Article
November 2018
3 Reads

The Prokineticins: Neuromodulators and Mediators of Inflammation and Myeloid Cell-Dependent Angiogenesis.

Physiol Rev 2018 04;98(2):1055-1082

Sapienza University of Rome, Rome, Italy ; and University of California, San Diego, La Jolla, California.

The mammalian prokineticins family comprises two conserved proteins, EG-VEGF/PROK1 and Bv8/PROK2, and their two highly related G protein-coupled receptors, PKR1 and PKR2. This signaling system has been linked to several important biological functions, including gastrointestinal tract motility, regulation of circadian rhythms, neurogenesis, angiogenesis and cancer progression, hematopoiesis, and nociception. Mutations in PKR2 or Bv8/PROK2 have been associated with Kallmann syndrome, a developmental disorder characterized by defective olfactory bulb neurogenesis, impaired development of gonadotropin-releasing hormone neurons, and infertility. Read More

View Article
April 2018
6 Reads

Novel interstitial deletion in Xp22.3 in a typical X-linked recessive family with Kallmann syndrome.

Andrologia 2018 Feb 14. Epub 2018 Feb 14.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Kallmann syndrome (KS) is a clinically and genetically heterogeneous condition characterised by hypogonadotropic hypogonadism with anosmia or hyposmia. More than nineteen genes causing KS have been reported to date. KAL1, first identified to causing the X-linked form of KS, accounts for 10%-20% of KS patients. Read More

View Article
February 2018

Sema3a plays a role in the pathogenesis of CHARGE syndrome.

Hum Mol Genet 2018 04;27(8):1343-1352

Institute of Human Genetics, University Medical Center Göttingen, 37073 Göttingen, Germany.

CHARGE syndrome is an autosomal dominant malformation disorder caused by heterozygous loss of function mutations in the chromatin remodeler CHD7. Chd7 regulates the expression of Sema3a, which also contributes to the pathogenesis of Kallmann syndrome, a heterogeneous condition with the typical features hypogonadotropic hypogonadism and an impaired sense of smell. Both features are common in CHARGE syndrome suggesting that SEMA3A may provide a genetic link between these syndromes. Read More

View Article
April 2018
3 Reads

An epidemiological study on the course of disease and therapeutic considerations in relapsing-remitting multiple sclerosis patients receiving injectable first-line disease-modifying therapies in Germany (EPIDEM).

Ther Adv Neurol Disord 2018 23;11:1756285617749802. Epub 2018 Jan 23.

Multiple Sklerose Zentrum Bamberg (MSZB), Bamberg, Germany.

Background: In relapsing-remitting multiple sclerosis (RRMS), 'no evidence of disease activity' (NEDA) is regarded as a key treatment goal. The increasing number of treatments allows for individualized treatment optimization in patients with suboptimal response to first-line disease-modifying therapies (DMTs). Therefore, monitoring of clinical and subclinical disease activity on DMTs has been recognized as an important component of long-term patient management. Read More

View Article
January 2018
11 Reads

Analysis of the human SOX10 mutation Q377X in mice and its implications for genotype-phenotype correlation in SOX10-related human disease.

Hum Mol Genet 2018 03;27(6):1078-1092

Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander Universität Erlangen-Nürnberg, D-91054 Erlangen, Germany.

Human SOX10 mutations lead to various diseases including Waardenburg syndrome, Hirschsprung disease, peripheral demyelinating neuropathy, central leukodystrophy, Kallmann syndrome and various combinations thereof. It has been postulated that PCWH as a combination of Waardenburg and Hirschsprung disease, peripheral neuropathy and central leukodystrophy is caused by heterozygous SOX10 mutations that result in the presence of a dominantly acting mutant SOX10 protein in the patient. One such protein with postulated dominant action is SOX10 Q377X. Read More

View Article
March 2018
2 Reads

GENETICS IN ENDOCRINOLOGY: Genetic counseling for congenital hypogonadotropic hypogonadism and Kallmann syndrome: new challenges in the era of oligogenism and next-generation sequencing.

Eur J Endocrinol 2018 Mar 12;178(3):R55-R80. Epub 2018 Jan 12.

University of Paris-SudParis-Sud Medical School, Le Kremlin-Bicêtre, France

Congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS) are rare, related diseases that prevent normal pubertal development and cause infertility in affected men and women. However, the infertility carries a good prognosis as increasing numbers of patients with CHH/KS are now able to have children through medically assisted procreation. These are genetic diseases that can be transmitted to patients' offspring. Read More

View Article
March 2018
3 Reads

Kallmann Syndrome and Chronic Myeloid Leukemia: A Rare Occurrence.

J Assoc Physicians India 2017 10;65(10):76

Associate Professor in General Medicine, Seth G.S. Medical College and K.E.M.H., Mumbai, Maharashtra.

View Article
October 2017
2 Reads

Update on the Genetics of Idiopathic Hypogonadotropic Hypogonadism.

J Clin Res Pediatr Endocrinol 2017 Dec 27;9(Suppl 2):113-122. Epub 2017 Dec 27.

University of Mississippi Medical Center, Department of Pediatrics, Division of Pediatric Endocrinology and Department of Neurobiology and Anatomical Sciences, Jackson, Mississippi, USA.

Traditionally, idiopathic hypogonadotropic hypogonadism (IHH) is divided into two major categories: Kallmann syndrome (KS) and normosmic IHH (nIHH). To date, inactivating variants in more than 50 genes have been reported to cause IHH. These mutations are estimated to account for up to 50% of all apparently hereditary cases. Read More

View Article
December 2017
4 Reads

Anosmin-1 is essential for neural crest and cranial placodes formation in Xenopus.

Biochem Biophys Res Commun 2018 01 22;495(3):2257-2263. Epub 2017 Dec 22.

Department of Basic Science & Craniofacial Biology, College of Dentistry, New York University, New York, USA. Electronic address:

During embryogenesis vertebrates develop a complex craniofacial skeleton associated with sensory organs. These structures are primarily derived from two embryonic cell populations the neural crest and cranial placodes, respectively. Neural crest cells and cranial placodes are specified through the integrated action of several families of signaling molecules, and the subsequent activation of a complex network of transcription factors. Read More

View Article
January 2018
2 Reads

WDR11-mediated Hedgehog signalling defects underlie a new ciliopathy related to Kallmann syndrome.

EMBO Rep 2018 02 20;19(2):269-289. Epub 2017 Dec 20.

Molecular and Clinical Sciences Research Institute, St. George's, University of London, London, UK

WDR11 has been implicated in congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS), human developmental genetic disorders defined by delayed puberty and infertility. However, WDR11's role in development is poorly understood. Here, we report that WDR11 modulates the Hedgehog (Hh) signalling pathway and is essential for ciliogenesis. Read More

View Article
February 2018
14 Reads
9.050 Impact Factor

Next-generation sequencing of patients with congenital anosmia.

Eur J Hum Genet 2017 12 13;25(12):1377-1387. Epub 2017 Nov 13.

Deptment of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.

We performed whole exome or genome sequencing in eight multiply affected families with ostensibly isolated congenital anosmia. Hypothesis-free analyses based on the assumption of fully penetrant recessive/dominant/X-linked models obtained no strong single candidate variant in any of these families. In total, these eight families showed 548 rare segregating variants that were predicted to be damaging, in 510 genes. Read More

View Article
December 2017
9 Reads

New intronic Fibroblast Growth Factor Receptor 1 (FGFR1) mutation leading to disrupted splicing and Kallmann syndrome.

Hum Reprod 2018 02;33(2):328-330

Faculty of Medicine, Department of Physiology, University of Helsinki, Haartmaninkatu 8, FI-00014 Helsinki, Finland.

Congenital hypogonadotropic hypogonadism (CHH), which can present with a defective sense of smell (Kallmann syndrome, KS), is a clinically and genetically heterogeneous disorder. Over 31 genes have been associated with CHH, but most of the patients still lack a molecular genetic diagnosis. Some cases may be explained by mutations that disrupt the splicing of already established CHH genes but that are unrecognized either because they are located deep in introns or are not predicted to disrupt splicing. Read More

View Article
February 2018
1 Read

The hypothalamus-pituitary-gonad axis: Tales of mice and men.

Metabolism 2018 Sep 6;86:3-17. Epub 2017 Dec 6.

Imperial College, London, UK. Electronic address:

Reproduction is controlled by the hypothalamic-pituitary-gonadal (HPG) axis. Gonadotropin-releasing hormone (GnRH) neurons play a central role in this axis through production of GnRH, which binds to a membrane receptor on pituitary gonadotrophs and stimulates the biosynthesis and secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Multiple factors affect GnRH neuron migration, GnRH gene expression, GnRH pulse generator, GnRH secretion, GnRH receptor expression, and gonadotropin synthesis and release. Read More

View Article
September 2018
4 Reads

A rare ANOS1 variant in siblings with Kallmann syndrome identified by whole exome sequencing.

Andrology 2018 Jan 6;6(1):53-57. Epub 2017 Dec 6.

Department of Urology, University of Miami, Miami, FL, USA.

Kallmann syndrome is a rare genetic condition causing congenital hypogonadotropic hypogonadism. It presents with delayed puberty, anosmia, and infertility. Here, we set out to identify a causative DNA variant for Kallmann syndrome in two affected brothers of Hispanic ancestry. Read More

View Article
January 2018
6 Reads

DCC/NTN1 complex mutations in patients with congenital hypogonadotropic hypogonadism impair GnRH neuron development.

Hum Mol Genet 2018 01;27(2):359-372

Endocrinology, Diabetes & Metabolism Service, Centre Hospitalier Universitaire Vaudois (CHUV), Faculty of Biology & Medicine, University of Lausanne, 1005 Lausanne, Switzerland.

Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disease characterized by absent puberty and infertility due to GnRH deficiency, and is often associated with anosmia [Kallmann syndrome (KS)]. The genetic etiology of CHH is heterogeneous, and more than 30 genes have been implicated in approximately 50% of patients with CHH. We hypothesized that genes encoding axon-guidance proteins containing fibronectin type-III (FN3) domains (similar to ANOS1, the first gene associated with KS), are mutated in CHH. Read More

View Article
January 2018
15 Reads

Reproductive endocrine phenotypes relating to CHD7 mutations in humans.

Am J Med Genet C Semin Med Genet 2017 12 20;175(4):507-515. Epub 2017 Nov 20.

Harvard Reproductive Endocrine Sciences Center of Excellence in Translation Research & Reproductive Endocrine Unit of the Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.

Mutations in the gene CHD7 cause CHARGE syndrome, a rare multi-organ syndromic disorder. Gonadal defects are common in individuals with CHARGE syndrome (seen in ∼60-80% of cases) and represent the letter "G" in the CHARGE syndrome acronym. The gonadal defect in CHARGE syndrome results from congenital deficiency of the hypothalamic hormone Gonadotropin-releasing hormone (GnRH), which manifests clinically as pubertal failure and infertility, and biochemically as hypogonadotropic hypogonadism (low sex steroid hormone levels with inappropriately normal or low gonadotropin levels). Read More

View Article
December 2017
7 Reads

Evaluating CHARGE syndrome in congenital hypogonadotropic hypogonadism patients harboring CHD7 variants.

Genet Med 2018 08 16;20(8):872-881. Epub 2017 Nov 16.

Endocrinology, Diabetology & Metabolism Service, Lausanne University Hospital, Lausanne, Switzerland.

Purpose: Congenital hypogonadotropic hypogonadism (CHH), a rare genetic disease caused by gonadotropin-releasing hormone deficiency, can also be part of complex syndromes (e.g., CHARGE syndrome). Read More

View Article
August 2018
21 Reads
7.330 Impact Factor

Kallmann syndrome: phenotype and genotype of hypogonadotropic hypogonadism.

Metabolism 2018 Sep 3;86:124-134. Epub 2017 Nov 3.

University of Patras Medical School, University Hospital, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, Rion, Patras, Achaia, Greece.

Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency (IGD) IGD is a genetically and clinically heterogeneous disorder. Mutations in many different genes are able to explain ~40% of the causes of IGD, with the rest of cases remaining genetically uncharacterized. While most mutations are inherited in X-linked, autosomal dominant, or autosomal recessive pattern, several IGD genes are shown to interact with each other in an oligogenic manner. Read More

View Article
September 2018
5 Reads

Induction of puberty with human chorionic gonadotropin (hCG) followed by reversal of hypogonadotropic hypogonadism in Kallmann syndrome.

Endokrynol Pol 2017 12;68(6):692-696. Epub 2017 Oct 12.

Dept. of Endocrinology, Aalborg University Hospital.

Introduction: Kallmann syndrome (KS) is a rare, congenital disorder combining hypogonadotropic hypogonadism (HH) due to GnRH-deficiency with anosmia. Traditionally thought to require lifelong therapy it turns out to be a reversible condition in some patients.

Case Report: We present a case of a 22-year old man with absent puberty due to KS, in whom genetic testing revealed heterozygosity for a mutation in the PROK2 gene. Read More

View Article
July 2018
6 Reads

Clinical characteristics of 138 Chinese female patients with idiopathic hypogonadotropic hypogonadism.

Endocr Connect 2017 Nov 10;6(8):800-810. Epub 2017 Oct 10.

Department of Obstetrics and GynecologyPeking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Science, Beijing, People's Republic of China.

Objective: To evaluate the clinical features of Chinese women with idiopathic hypogonadotropic hypogonadism (IHH).

Methods: We retrospectively reviewed the clinical characteristics, laboratory and imaging findings, therapeutic management and fertility outcomes of 138 women with IHH. All patients had been treated and followed up at an academic medical centre during 1990-2016. Read More

View Article
November 2017
29 Reads

Transcription Factors Sp8 and Sp9 Coordinately Regulate Olfactory Bulb Interneuron Development.

Cereb Cortex 2018 Sep;28(9):3278-3294

Department of Translational Neuroscience, Shanghai Pudong Hospital, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China.

Neural stem cells in the postnatal telencephalic ventricular-subventricular zone (V-SVZ) generate new interneurons, which migrate tangentially through the rostral migratory stream (RMS) into the olfactory bulb (OB). The Sp8 and Sp9 transcription factors are expressed in neuroblasts, as well as in the immature and mature interneurons in the V-SVZ-RMS-OB system. Here we show that Sp8 and Sp9 coordinately regulate OB interneuron development: although Sp9 null mutants show no major OB interneuron defect, conditional deletion of both Sp8 and Sp9 resulted in a much more severe reduction of OB interneuron number than that observed in the Sp8 conditional mutant mice, due to defects in neuronal differentiation, tangential and radial migration, and increased cell death in the V-SVZ-RMS-OB system. Read More

View Article
September 2018
20 Reads

The terminal nerve plays a prominent role in GnRH-1 neuronal migration independent from proper olfactory and vomeronasal connections to the olfactory bulbs.

Biol Open 2017 Oct 15;6(10):1552-1568. Epub 2017 Oct 15.

Department of Biological Sciences, University at Albany, Albany, NY 12222, USA

Gonadotropin-releasing hormone-1 (GnRH-1) neurons (GnRH-1 ns) migrate from the developing olfactory pit into the hypothalamus during embryonic development. Migration of the GnRH-1 neurons is required for mammalian reproduction as these cells control release of gonadotropins from the anterior pituitary gland. Disturbances in GnRH-1 ns migration, GnRH-1 synthesis, secretion or signaling lead to varying degrees of hypogonadotropic hypogonadism (HH), which impairs pubertal onset and fertility. Read More

View Article
October 2017

Spectral signatures of mirror movements in the sensori-motor connectivity in kallmann syndrome.

Hum Brain Mapp 2018 01 30;39(1):42-53. Epub 2017 Sep 30.

Department of Medicine, Surgery and Dentistry, Scuola Medica Salernitana, University of Salerno, Baronissi, Salerno, Italy.

Mirror movements (MM) might be observed in congenital and acquired neurodegenerative conditions but their anatomic-functional underpinnings are still largely elusive. This study investigated the spectral changes of resting-state functional connectivity in Kallmann Syndrome (hypogonadotropic hypogonadism with hypo/anosmia with or without congenital MM) searching for insights into the phenomenon of MM. Forty-four Kallmann syndrome patients (21 with MM) and 24 healthy control subjects underwent task (finger tapping) and resting-state functional MRI. Read More

View Article
January 2018
8 Reads

Molecular genetic and clinical delineation of 22 patients with congenital hypogonadotropic hypogonadism.

J Pediatr Endocrinol Metab 2017 Oct;30(10):1111-1118

.

Background: Congenital hypogonadotropic hypogonadism (CHH) is classified as Kallmann syndrome (KS) with anosmia/hyposmia or normosmic (n)CHH. Here, we investigated the genetic causes and phenotype-genotype correlations in Japanese patients with CHH.

Methods: We enrolled 22 Japanese patients with CHH from 21 families (18 patients with KS and 4 with nCHH) and analyzed 27 genes implicated in CHH by next-generation and Sanger sequencing. Read More

View Article
October 2017
17 Reads

Characteristics of a nationwide cohort of patients presenting with isolated hypogonadotropic hypogonadism (IHH).

Eur J Endocrinol 2018 Jan 7;178(1):23-32. Epub 2017 Sep 7.

Department of Clinical Sciences and Community HealthUniversity of Milan, Milan, Italy.

Objective: Isolated hypogonadotropic hypogonadism (IHH) is a rare disorder with pubertal delay, normal (normoosmic-IHH, nIHH) or defective sense of smell (Kallmann syndrome, KS). Other reproductive and non-reproductive anomalies might be present although information on their frequency are scanty, particularly according to the age of presentation.

Design: Observational cohort study carried out between January 2008 and June 2016 within a national network of academic or general hospitals. Read More

View Article
January 2018
77 Reads