1/8. An atypical contiguous gene syndrome: molecular studies in a family with X-linked Kallmann's syndrome and X-linked ichthyosis.BACKGROUND AND OBJECTIVE: Kallmann's syndrome (KS) is characterized by hypogonadotrophic hypogonadism in association with anosmia or hyposmia. This entity can be associated with X-linked ichthyosis (XLI) in a contiguous gene syndrome. Genetic defects have been demonstrated on the Xp22.3 region explaining the presence of one or both entities in affected individuals. In this report we describe the molecular findings in four patients, pertaining to a three generation family, with KS which was associated with XLI in two of them. MEASUREMENTS: Enzymatic activity of steroid sulphatase was measured in leucocytes. polymerase chain reaction of the 14 exons of the Kallmann gene (KAL) and of the 5' and 3' extremes of the steroid sulphatase gene was performed in genomic dna. PCR products of the 14 exons of the KAL gene were purified and sequenced. RESULTS: Absence of steroid sulphatase activity and a complete deletion of the STS gene were demonstrated in both patients with XLI. In all subjects, the 14 KAL gene exons amplified in a normal fashion; no mutation was documented after sequencing all exons. CONCLUSIONS: Although it has been proposed recently that the X-linked form of the disease accounts for the minority of patients with Kallman's syndrome, the pedigree chart of this family demonstrates this inheritance pattern. Various possibilities are mentioned in order to explain the absence of mutation in the KAL gene. The coexistence, in this family, of Kallman's syndrome individuals and patients with Kallman's syndrome and X-linked ichthyosis is discussed.- - - - - - - - - - ranking = 1keywords = sulphatase (Clic here for more details about this article) |
2/8. Kallmann's syndrome: is it always for life?OBJECTIVE: Kallmann's syndrome (KS) is defined by the association of olfactory deficit with irreversible, congenital gonadotrophin deficiency (IHH). We present evidence for the existence of a variant form of KS, in which endogenous gonadotrophin secretion recovers spontaneously in later life. DESIGN: Longitudinal clinical study. patients: Five men with anosmia or severe hyposmia, who originally presented in their late teens or early twenties as a result of severe pubertal delay and were thus presumed to have KS. RESULTS: Spontaneous onset of endogenous gonadotrophin secretion, evidenced by progressive normalization of testicular volume and of serum testosterone concentration, occurred in these men over a period of years following the initial diagnosis. CONCLUSIONS: This variant form of Kallman's syndrome is not well recognized and may well be under-diagnosed. Once full virilization has been induced, males with congenital gonadotrophin deficiency whose testes have significantly increased in size should be reassessed, off androgen replacement therapy, to identify those who no longer require treatment.- - - - - - - - - - ranking = 0.00038689708709346keywords = deficiency (Clic here for more details about this article) |
3/8. A case of primary amenorrhea, diabetes and anosmia.This case details a patient with primary amenorrhea with an unusual cause. She presented at age 16 with short stature, minimal sexual development and no prior menses. Her history was significant for poorly controlled type 1 diabetes. She had been evaluated previously for growth hormone deficiency, and had received a short course of growth hormone therapy. Of greatest significance was the fact that she had also had a decreased sense of smell since her youth. Although a previous computerized tomography scan had been reported as normal, follow-up magnetic resonance imaging demonstrated the absence of olfactory bulbs. smell testing confirmed the absence of smell and testing of gonadotropin releasing hormone demonstrated an inadequate response. All of these features suggested kallmann syndrome. This syndrome commonly presents with delayed onset of puberty and decreased or absent sense of smell. There are also many associated features, and the disease is remarkable for its great genotypic and phenotypic variability. Current understanding of its pathogenesis, the commonly associated features of kallmann syndrome and the impact of diabetes on growth and sexual development are reviewed.- - - - - - - - - - ranking = 0.00019344854354673keywords = deficiency (Clic here for more details about this article) |
4/8. Kallmann's syndrome: clues to clinical diagnosis.Hypogonadotropic patients may visit pediatricians, general practitioners, endocrinologists or urologists, presenting with microphallus, cryptochidism or pubertas tarda and delayed bone maturation. Congenital hypogonadotropic hypogonadism is characterized, apart from small testes, by the constellation of low serum levels of testosterone, LH and FSH. Kallman's syndrome is characterized by congenital hypogonadotropic hypogonadism with midline defects such as anosmia (a deficiency of the sense of smell). The first case report dates back to 1856, and genetic defects causing the syndrome have been recently described. The diagnosis can be clinically suspected and is established by confirming hormonal studies.- - - - - - - - - - ranking = 0.00019344854354673keywords = deficiency (Clic here for more details about this article) |
5/8. Atypical presentation of a patient with both kallmann syndrome and a craniopharyngioma: case report and literature review.OBJECTIVE: To describe an unusual presentation of a patient with kallmann syndrome, without the typical eunuchoid features, who had additional hormonal abnormalities caused by a craniopharyngioma. methods: This patient's clinical features, endocrine evaluation, and treatment are described, and the literature regarding kallmann syndrome is reviewed. The expected phenotype of kallmann syndrome is contrasted with this case presentation. A literature search was also performed to determine whether the combination of craniopharyngioma and Kallmann syndrome had been described previously. RESULTS: A 23-year-old man had a suprasellar tumor in conjunction with hypogonadotropic hypogonadism and growth hormone deficiency. Subsequently, he was also noted to have anosmia, a cleft palate, and bilateral olfactory bulb hypoplasia. His height was less than his calculated midparental height and exceeded his arm span. Defective neuronal migration in kallmann syndrome is caused by absence of adhesion proteins needed for cellular, neuronal, and axonal guidance. This results in failure of olfactory and gonadotropin-releasing hormone neurons to complete normal migration. Defective migration can also cause midline craniofacial abnormalities, renal agenesis, and cardiovascular defects. arachnoid cysts have been reported in two patients with kallmann syndrome, although whether a migration defect underlies their occurrence is speculative. No prior reports of craniopharyngioma in a patient with kallmann syndrome could be identified. CONCLUSION: It is postulated that although this patient had kallmann syndrome, he did not present with a eunuchoid body habitus because of concomitant growth hormone deficiency caused by his craniopharyngioma. Although midline craniofacial abnormalities have been seen in patients with kallmann syndrome, this patient's craniopharyngioma seems more likely to be coincidental, rather than being one of the developmental anomalies that are part of the spectrum of this syndrome.- - - - - - - - - - ranking = 0.00038689708709346keywords = deficiency (Clic here for more details about this article) |
6/8. Case report: olfactory function in a fertile eunuch with kallmann syndrome.The olfactory and gonadal dysfunction in kallmann syndrome share a common embryologic pathophysiology. To characterize further the linkage between the hypogonadotropic hypogonadism and anosmia, the authors performed a detailed evaluation of olfactory function in a patient with Kallman Syndrome having the rare variant of partial gonadotropin deficiency (fertile eunuch). The subject was seen initially at age 16 years because of delayed puberty. He received testosterone replacement therapy and subsequently completed pubertal development. As an adult, while untreated, he had subnormal levels of serum testosterone, low gonadotropins, and normal response to luteinizing hormone- releasing hormone. He also had impotence that was reversible with testosterone therapy, and a normal sperm count. Despite the mild degree of hypogonadism, olfactory function was completely absent, and the response to nasal trigeminal stimulants was markedly attenuated. Complete anosmia may therefore be associated with gonadotropin deficiency that is only partial; the presence of anosmia does not predict the need for gonadotropin therapy to attain fertility.- - - - - - - - - - ranking = 0.00038689708709346keywords = deficiency (Clic here for more details about this article) |
7/8. X-linked ichthyosis with hypogonadism: not always Kallmann's syndrome.We describe two males with congenital ichthyosis secondary to steroid sulphatase deficiency who also manifested delayed puberty with biochemical features of hypogonadotrophic hypogonadism. In the first patient a history of cryptorchidism and the clinical findings of anosmia, micropenis and bimanual synkinesis suggested a contiguous gene syndrome, comprising X-linked Kallmann's syndrome and X-linked ichthyosis. An X-Y chromosomal translocation involving the Xp22.3 locus was identified; deletions of the STS locus and of exons 10-14 of the KAL locus were subsequently demonstrated. The second patient was euosmic and, although the STS locus was deleted in association with a pericentric inversion involving Xp22.3, no deletions were detected at the KAL locus. Clinically, he was felt to have constitutionally delayed puberty rather than hypogonadotropic hypogonadism and this diagnosis was substantiated by his subsequent development.- - - - - - - - - - ranking = 0.33352678187688keywords = sulphatase, deficiency (Clic here for more details about this article) |
8/8. Contiguous gene syndrome due to deletion of the first three exons of the Kallmann gene and complete deletion of the steroid sulphatase gene.OBJECTIVE: Large terminal or interstitial deletions of the 22.3 region on the short arm of the x chromosome cause contiguous gene syndromes. kallmann syndrome (hypogonadotrophic hypogonadism with anosmia or hyposmia) associated with X-linked ichthyosis, due to a contiguous gene syndrome, is an uncommon finding. Genetic defects have been demonstrated in the Xp22.3 region, explaining the presence of one or both entities in affected individuals. In this report we describe the molecular findings of a patient with kallmann syndrome and X-linked ichthyosis. PATIENT: A 20-year-old subject with hypogonadism, anosmia and generalized ichthyosis was studied endocrinologically, biochemically and molecularly. MEASUREMENTS: Levels of LH, FSH, GH, testosterone, oestradiol and cortisol were determined basally and after specific stimulation tests. Enzymatic activity of steroid sulphatase was measured in leucocytes. polymerase chain reaction of the 14 exons of the Kallmann gene and of the 5' and 3' extremes of the steroid sulphatase gene was performed in genomic dna. RESULTS: A partial deletion from exon 1 to exon 3 of the Kallmann gene, as well as a complete deletion of the steroid sulphatase gene were observed. CONCLUSIONS: A patient bearing a contiguous gene syndrome with partial deletion of the kallmann syndrome gene and complete deletion of the steroid sulphatase gene is described. This is the first time a mutation in the conserved cysteine-rich N-terminal region which corresponds to the whey acidic protein motif of the Kallmann gene has been characterized, thus demonstrating the importance of this specific region for the function of the gene.- - - - - - - - - - ranking = 2.6666666666667keywords = sulphatase (Clic here for more details about this article) |