Faculty Opinions recommendation of The prevalence of digenic mutations in patients with normosmic hypogonadotropic hypogonadism and Kallmann syndrome.

Abstract The first mutation in a gene associated with a neuronal migration disorder was identified in patients with Kallmann Syndrome, characterized by hypogonadotropic hypogonadism and anosmia. This pathophysiological association results from a defect in the development of the GnRH and the olfactory system. A recent genetic screening of Kallmann Syndrome patients revealed a novel mutation in CCDC141. Little is known about CCDC141, which encodes a coiled-coil domain containing protein. Here, we show that Ccdc141 is expressed in GnRH neurons and olfactory fibers and that knockdown of Ccdc141 reduces GnRH neuronal migration. Our findings in human patients and mouse models predict that CCDC141 takes part in embryonic migration of GnRH neurons enabling them to form a hypothalamic neuronal network to initiate pulsatile GnRH secretion and reproductive function.

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Clinicohormonal Parameters as a Primary Step to Differentiate Normosmic Idiopathic Hypogonadotropic Hypogonadism and Kallmann Syndrome in a Tertiary Care Hospital in Eastern India

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2021/48672.15128 ◽

2021 ◽

Author(s):

Ram Chandra Bhadra ◽

Dona Saha ◽

Arjun Baidya

Keyword(s):

Genetic Disorder ◽

Hormone Replacement ◽

Hypogonadotropic Hypogonadism ◽

Tertiary Care ◽

Serum Testosterone ◽

Kallmann Syndrome ◽

Care Hospital ◽

Cross Sectional ◽

Idiopathic Hypogonadotropic Hypogonadism ◽

Male Predominance

Introduction: Idiopathic hypogonadotropic hypogonadism is a rare gonadal dysgenesis in which puberty does not take place naturally. It occurs due to insufficient pulsatile secretion of Gonadotrophin-Releasing Hormone (GnRH) and the resulting Follicle-Stimulating Hormone (FSH) and Luteinising Hormone (LH) deficiency leads to absence of or delayed sexual maturation. Kallmann syndrome is an uncommon genetic disorder characterised by hypogonadotropic hypogonadism associated with anosmia or hyposmia. When anosmia is absent, the same is referred as normosmic Idiopathic Hypogonadotropic hypogonadism (nIHH). Aim: To find out the significant differences between Kallmann syndrome and nIHH based on clinical features and biochemical assessment as a primary measure to initiate the treatment early. Materials and Methods: This hospital based cross-sectional observational cohort study was conducted in Department of Endocrinology, Nilratan Sircar Medical College and Hospital, Kolkata, India. The study was done on 55 cases of IHH presenting to the department with delayed secondary sexual characteristics. Results: Out of these 55 cases, 45 (81.8%) were of nIHH and only 10 (18.2%) cases were of Kallmann Syndrome. It was found that both the conditions show male predominance. Smell abnormalities were present only in Kallmann group. The level of serum testosterone was significantly higher (p<0.05) in nIHH subjects (mean-35.59 ng/dL) than patients with Kallmann Syndrome (mean-14.90 ng/dL). Patients with Kallmann syndrome showed significantly reduced pubic and axillary hair development and absence of gonadal development. Conclusion: Absence of puberty with anosmia/hyposmia with low serum FSH and LH, drastically reduced serum testosterone, are factors that point towards the diagnosis of Kallmann syndrome even in absence of genetic study, which is helpful for initiation of hormone replacement therapy for treatment.

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Amenorrea primaria

Revista Colombiana de Obstetricia y Ginecología ◽

10.18597/rcog.354 ◽

2009 ◽

Vol 60 (1) ◽

pp. 57-67

Author(s):

Janer Sepúlveda-Agudelo ◽

Miguel Ángel Alarcón-Nivia ◽

Hermes Jaimes-Carvajal

Keyword(s):

Turner Syndrome ◽

Hypogonadotropic Hypogonadism ◽

Kallmann Syndrome ◽

Primary Amenorrhea ◽

Menstrual Disorders ◽

Palabras Clave

Objetivo: se hace una revisión detallada de la amenorreaprimaria, teniendo como base la clasificación propuesta por Mashchak CA y col. de acuerdo con la presencia o ausencia del desarrollo mamario y la presencia o no de útero, por ser la de mayor utilidad para el enfoque de manejo de las pacientes con amenorrea primaria.Metodología: se realizó una búsqueda de la literatura publicada en inglés a través de MEDLINE y OVID, usando como palabras clave: amenorrhea, primary amenorrhea, menstrual disorders, Turner syndrome, Kallmann syndrome, Prader-Willi síndrome, hypogonadotropic-hypogonadism; y se clasificó la información como soporte de la presente revisión, realizando resúmenes para su análisis.Resultados: la amenorrea primaria puede ser causada por una variedad de alteraciones que incluyen anormalidades müllerianas, gonadales, hipofisiarias, hipotalámicas, adrenales y tiroideas, o disfunciones hormonales en estos diferentes niveles. Estas anormalidades pueden ser congénitas por defectos cromosómicos o genéticos, o adquiridas, por lo tanto, es importante realizar un diagnóstico certero de esta patología para llevar a cabo un enfoque terapéutico adecuado, con el fin de disminuir todas las consecuencias que la enfermedad puede causar. Conclusiones: el tratamiento de las pacientes con amenorrea primaria debe ser individualizado, de acuerdo con las posibilidades terapéuticas de cada paciente, pero existen unas preguntas generales que tienen todas las pacientes o sus familiares y son relacionadas con la menstruación y los ciclos menstruales espontáneos posteriores, fertilidad, sexualidad y posibilidad de coitos con penetración vaginal satisfactoria.

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Kallmann syndrome in a 17-year-old boy

Kuban Scientific Medical Bulletin ◽

10.25207/1608-6228-2020-27-1-126-134 ◽

2020 ◽

Vol 27 (1) ◽

pp. 126-134

Author(s):

Alla V. Burlutskaya ◽

Ol’ga G. Korobkina ◽

Anastasiya V. Statova

Keyword(s):

Sexual Development ◽

Hypogonadotropic Hypogonadism ◽

Brain Mri ◽

Hormonal Treatment ◽

Psychological Adaptation ◽

Bone Age ◽

Hereditary Disease ◽

Kallmann Syndrome ◽

Timely Initiation ◽

Clinical Hospital

Aim. To describe a rare hereditary disease — Kallmann syndrome — in a 17-year-old boy.Materials and methods. A retrospective analysis of anamnestic information, the course of the disease, laboratory and instrumental data and treatment of a 17-year-old patient with Kallmann syndrome was carried out. The patient underwent treatment in a gastroenterological department of the Children’s Regional Clinical Hospital in Krasnodar in March 2019.Results. Patient K., 17 years old, was admitted to the gastroenterological department of the Children’s Regional Clinical Hospital in March 2019 with complaints of weakness, nausea, “hungry” abdominal pain and decreased appetite. Upon examination, the child revealed duodenal ulcer. However, an in-depth examination found that the boy was lagging behind in physical and sexual development. In this connection, an endocrinological examination was performed, which discovered: a decrease in the concentration of sex hormones relative to the age norm (luteinizing hormone, follicle-stimulating hormone, testosterone), delayed bone age as compared to the passport age, discrepancy between the testicular size and the patient’s age, olfactory bulb hypoplasia according to brain MRI, 1st degree smell disorder, the presence of a mutation in the KAL1 gene. The boy was diagnosed with: Kallmann syndrome, X-linked recessive inheritance. Complications: hypogonadotropic hypogonadism. The chosen treatment included prolonged testosterone esters for parenteral administration of 250 mg once per 3–4 weeks. Following 6 months of therapy, positive signs were observed: an increase in height by 2 cm, an increase in testicular volume by 3 ml, the appearance of single hairs at the base of the penis.Conclusion. Kallmann syndrome is a rare pathology, whose main manifestations include delayed sexual development and hypo- or anosmia. For a timely diagnosis and treatment, it is of great importance to identify symptoms and conduct a comprehensive examination. Timely initiation of hormonal treatment allows puberty to occur in all cases, thus facilitating social and psychological adaptation of such patients.

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