web contact: pietsch@indiana.edu
TITLE: Genetics of human hypogonadotropic hypogonadism.
AUTHOR(S): Layman-LC
ADDRESS OF AUTHOR: Section of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Medical College of Georgia, Augusta 30912-3360, USA.
SOURCE (BIBLIOGRAPHIC CITATION): Am-J-Med-Genet. 1999 Dec 29; 89(4): 240-8
INTERNATIONAL STANDARD SERIAL NUMBER: 0148-7299
PUBLICATION YEAR: 1999
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: Humans with hypogonadotropic hypogonadism (HH) manifest irreversible pubertal delay, infertility, and low serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Although the genetic basis of this condition is largely unknown, mutations have been identified in approximately 5-10% of HH patients. Mutations in the KAL gene (Kallmann syndrome) and the AHC gene (adrenal hypoplasia congenita/HH) cause X-linked recessive HH. Autosomal recessive HH may be brought about by mutations in the gonadotropin-releasing hormone receptor, leptin, and the leptin receptor genes. Isolated deficiencies of the gonadotropins FSH and LH are due to corresponding beta-subunit genes. PROP1 gene mutations lead to combined pituitary deficiency, and HESX gene mutations result in septo-optic dysplasia, both of which include HH. These identified gene mutations advance our understanding of normal hypothalamic-pituitary-gonadal function. Copyright 2000 Wiley-Liss, Inc.
MINOR MESH HEADINGS: DNA-Binding-Proteins-genetics; FSH-blood; FSH-deficiency; FSH-genetics; Genes,-Homeobox; Genes,-Recessive; Homeodomain-Proteins-genetics; Hypogonadism-blood; Hypogonadism-diagnosis; Hypogonadism-etiology; Hypothalamo-Hypophyseal-System-metabolism; Kallmann-Syndrome-genetics; Leptin-genetics; LH-blood; LH-deficiency; LH-genetics; Mutation-; Nerve-Tissue-Proteins-genetics; Receptors,-LHRH-genetics; Receptors,-Retinoic-Acid-genetics; Transcription-Factors-genetics
MAJOR MeSH HEADINGS: *Gonadotropins-deficiency; *Hypogonadism-genetics
CHECKTAGS: Female; Human; Male; Support,-U.S.-Gov't,-P.H.S.
PUBLICATION TYPE: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
CONTRACT OR GRANT NUMBERS: HD33004HDNICHD
CAS REGISTRY NUMBER OR EC NUMBER: 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 9002-67-9; 9002-68-0
NAME OF SUBSTANCE: DAX-1-protein; DNA-Binding-Proteins; Gonadotropins; Homeodomain-Proteins; KAL-X-protein; Leptin; Nerve-Tissue-Proteins; PROP1-protein; Receptors,-LHRH; Receptors,-Retinoic-Acid; Transcription-Factors; LH; FSH
MEDLINE ACCESSION NUMBER: 20193405
UPDATE CODE: 200008
Record 2 of 11 in MEDLINE EXPRESS (R) 2000/01-2000/09
TITLE: Septo-optic dysplasia plus: a spectrum of malformations of cortical development.
AUTHOR(S): Miller-SP; Shevell-MI; Patenaude-Y; Poulin-C; O'Gorman-AM
ADDRESS OF AUTHOR: Departments of Neurology & Neurosurgery, McGill University, Montreal, Quebec, Canada.
SOURCE (BIBLIOGRAPHIC CITATION): Neurology. 2000 Apr 25; 54(8): 1701-3
INTERNATIONAL STANDARD SERIAL NUMBER: 0028-3878
PUBLICATION YEAR: 2000
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: The authors describe three children with septo-optic dysplasia (SOD)-plus: SOD and an associated malformation of cortical development. All three children had developmental delay, and two of the children had significant associated motor deficits. The associated cortical malformations with SOD include a spectrum of disorders of neuronal organization, not limited, as previously described, to schizencephaly. SOD-plus should be suspected in children with SOD and developmental delay.
MINOR MESH HEADINGS: Brain-Diseases-complications; Cerebral-Cortex-growth-and-development; Cerebral-Cortex-pathology; Child-; Child,-Preschool; Cochlea-abnormalities; Cochlea-pathology; Developmental-Disabilities-diagnosis; Developmental-Disabilities-etiology; Electroencephalography-; Magnetic-Resonance-Imaging; Optic-Chiasm-abnormalities; Optic-Chiasm-pathology; Optic-Nerve-Diseases-complications; Paresis-etiology; Septum-Pellucidum-pathology; Septum-Pellucidum-radiography; Tomography,-X-Ray-Computed
MAJOR MeSH HEADINGS: *Abnormalities,-Multiple-diagnosis; *Brain-Diseases-diagnosis; *Cerebral-Cortex-abnormalities; *Optic-Nerve-Diseases-diagnosis; *Septum-Pellucidum-abnormalities
CHECKTAGS: Case-Report; Female; Human; Male
PUBLICATION TYPE: JOURNAL-ARTICLE
MEDLINE ACCESSION NUMBER: 20227887
UPDATE CODE: 200007
SUBSET: AIM
Record 3 of 11 in MEDLINE EXPRESS (R) 2000/01-2000/09
TITLE: Ophthalmological and intracranial anomalies in patients with clinical anophthalmos.
AUTHOR(S): Jacquemin-C; Mullaney-PB; Bosley-TM
ADDRESS OF AUTHOR: Radiology Department, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
SOURCE (BIBLIOGRAPHIC CITATION): Eye. 2000 Feb; 14 ( Pt 1): 82-7
INTERNATIONAL STANDARD SERIAL NUMBER: 0950-222X
PUBLICATION YEAR: 2000
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: ENGLAND
ABSTRACT: PURPOSE: To better describe the clinical and neuroimaging spectrum of abnormalities in clinical anophthalmos. METHODS: We performed a retrospective review of all 17 patients admitted to the King Khaled Eye Specialist Hospital with clinical anophthalmos over a 15 year period who had a complete ophthalmological examination documented and received computed tomographic (CT) imaging of the orbits and brain. RESULTS: Patients with clinical anophthalmos had a high incidence of developmental abnormalities involving both eyes (15/17 patients, 88%), the brain (12/17 patients, 71%) and the body (7/12, 58%). The incidence of central nervous system anomalies reached 100% in patients with bilateral small optic nerves on CT scan. CONCLUSIONS: Patients with clinical anophthalmos share a similar constellation of neurological, somatic and neuroradiological abnormalities as patients with microphthalmos, septo-optic dysplasia and clinical optic nerve hypoplasia. This fact may provide insight into developmental abnormalities of the afferent visual system and brain.
MINOR MESH HEADINGS: Adult-; Child-; Child,-Preschool; Eye-Abnormalities-radiography; Infant-; Infant,-Newborn; Microphthalmos-radiography; Optic-Nerve-abnormalities; Retrospective-Studies; Tomography,-X-Ray-Computed
MAJOR MeSH HEADINGS: *Abnormalities,-Multiple-radiography; *Anophthalmos-radiography; *Brain-abnormalities
CHECKTAGS: Female; Human; Male
PUBLICATION TYPE: JOURNAL-ARTICLE
MEDLINE ACCESSION NUMBER: 20217909
UPDATE CODE: 200007
Record 4 of 11 in MEDLINE EXPRESS (R) 2000/01-2000/09
TITLE: HESX1: a novel gene implicated in a familial form of septo-optic dysplasia.
AUTHOR(S): Dattani-MT; Martinez-Barbera-JP; Thomas-PQ; Brickman-JM; Gupta-R; Wales-JK; Hindmarsh-PC; Beddington-RS; Robinson-IC
ADDRESS OF AUTHOR: London Centre for Paediatric Endocrinology and Metabolism, Institute of Child Health, UK. m.dattani@ich.ucl.ac.uk
SOURCE (BIBLIOGRAPHIC CITATION): Acta-Paediatr-Suppl. 1999 Dec; 88(433): 49-54
INTERNATIONAL STANDARD SERIAL NUMBER: 0803-5326
PUBLICATION YEAR: 1999
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: NORWAY
ABSTRACT: The homeobox gene Hesx1, which encodes a pituitary transcription factor, is first expressed at gastrulation in the mouse embryo. Hesx1 expression begins in prospective forebrain tissue but later becomes restricted to Rathke's pouch, the primordium of the anterior pituitary gland. Transgenic mice lacking Hesx1 exhibit a phenotype comprising variable anterior CNS defects, such as a reduced prosencephalon, abnormalities in the corpus callosum and septum pellucidum, anophthalmia or microphthalmia, defective olfactory development and bifurcations in Rathke's pouch with pituitary dysplasia. A comparable and highly variable phenotype in humans is septo-optic dysplasia. We have cloned and sequenced the human homologue HESX1 and screened for mutations in affected individuals using single-stranded conformational polymorphism analysis. Two siblings with septo-optic dysplasia were homozygous for a missense mutation within the HESX1 homeobox. This mutation resulted in the substitution of a highly conserved arginine residue (Arg53) by cysteine and led to a loss of in vitro DNA binding. Hence, a vital role for Hesx1/HESX1 in forebrain and pituitary development in mice and humans is suggested.
MINOR MESH HEADINGS: Arginine-genetics; Cysteine-genetics; Genotype-; Mutation,-Missense; Phenotype-; Pituitary-Gland,-Anterior-physiology; Prosencephalon-physiology; Transcription,-Genetic
MAJOR MeSH HEADINGS: *Genes,-Homeobox; *Helix-Loop-Helix-Motifs-genetics; *Homeodomain-Proteins-genetics; *Septum-Pellucidum-abnormalities
CHECKTAGS: Animal; Human
PUBLICATION TYPE: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
CAS REGISTRY NUMBER OR EC NUMBER: 0; 149348-15-2; 52-90-4; 7004-12-8
NAME OF SUBSTANCE: Homeodomain-Proteins; HES-1-protein; Cysteine; Arginine
MEDLINE ACCESSION NUMBER: 20089971
UPDATE CODE: 200003
Record 5 of 11 in MEDLINE EXPRESS (R) 2000/01-2000/09
TITLE: Heritable disorders of pituitary development.
AUTHOR(S): Parks-JS; Brown-MR; Hurley-DL; Phelps-CJ; Wajnrajch-MP
ADDRESS OF AUTHOR: Department of Pediatrics, Emory University, Atlanta, Georgia 30322, USA. jparks@emory.edu
SOURCE (BIBLIOGRAPHIC CITATION): J-Clin-Endocrinol-Metab. 1999 Dec; 84(12): 4362-70
INTERNATIONAL STANDARD SERIAL NUMBER: 0021-972X
PUBLICATION YEAR: 1999
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: Basic and translational research achievements over the past 2 decades have disclosed the molecular mechanisms underlying several genetic forms of hypopituitarism. Disorders that are limited to the hypothalamic, pituitary, GH axis are caused by mutations in individual components of that axis. Disorders involving GH and one or more additional pituitary hormones are caused by mutations in the homeodomain transcription factors that direct embryological development of the anterior pituitary gland. Pit-1 has a POU-specific and a POU-homeo DNA-binding domain. The phenotype produced by mutations in the PIT1 gene involves deficiencies of GH, PRL, and TSH. Pituitary glands are either small or normally sized. The PROP1 gene encodes a transcription factor with a single paired-like DNA-binding domain. Persons with inactivating mutations in PROP1 have deficiencies of LH and FSH, as well as GH, PRL, and TSH. Their pituitary glands may be small, normally sized, or extremely large and show suprasellar extension. Pituitary degeneration may produce acquired deficiency of ACTH. Expression of the HESX1 gene precedes expression of PROP1 and PIT1, and it is much more widespread. The protein has a paired-like domain, and it competes with the product of PROP1 for DNA-binding. Homozygosity for inactivating mutations of HESX1 produces a complex phenotype that resembles septo-optic dysplasia. Much more needs to be learned about the role of HESX1 mutations in other forms of hypopituitarism.
MINOR MESH HEADINGS: Carrier-Proteins-genetics; Homeodomain-Proteins-genetics; Mutation-; Transcription-Factors-genetics
MAJOR MeSH HEADINGS: *Hypopituitarism-genetics; *Pituitary-Gland-growth-and-development
CHECKTAGS: Human; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-Non-P.H.S.; Support,-U.S.-Gov't,-P.H.S.
PUBLICATION TYPE: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
CONTRACT OR GRANT NUMBERS: NS25987NSNINDS; DK02569DKNIDDK
CAS REGISTRY NUMBER OR EC NUMBER: 0; 0; 0; 0; 0; 149348-15-2
NAME OF SUBSTANCE: phosphatidylinositol-exchange-protein; Carrier-Proteins; Homeodomain-Proteins; PROP1-protein; Transcription-Factors; HES-1-protein
MEDLINE ACCESSION NUMBER: 20066672
UPDATE CODE: 200003
SUBSET: AIM
Record 6 of 11 in MEDLINE EXPRESS (R) 2000/01-2000/09
TITLE: Transcription factors regulating pituitary development.
AUTHOR(S): Parks-JS; Brown-MR
ADDRESS OF AUTHOR: Division of Pediatric Endocrinology and Diabetes, Emory University School of Medicine, Atlanta, GA 30322, USA. jparks@emory.edu
SOURCE (BIBLIOGRAPHIC CITATION): Growth-Horm-IGF-Res. 1999 Jun; 9 Suppl B: 2-8; discussion 8-11
INTERNATIONAL STANDARD SERIAL NUMBER: 1096-6374
PUBLICATION YEAR: 1999
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: SCOTLAND
ABSTRACT: This review will address contributions of nuclear transcription factors to the embryologic development and definitive function of the anterior pituitary gland. The HESX1, PITX1, PITX2, PROP1 and POU1F1 genes are of particular interest because of their recognized or potential associations with human disease. Mutations of any of the first three genes produce complex disease phenotypes such as septo-optic dysplasia, Treacher Collins Franceschetti syndrome or Rieger syndrome that may include deficiency of one or more pituitary hormones. Mutations in PROP1 or POU1F1, or their mouse homologous, result in severe hypopituitarism as well as morphological abnormalities of the pituitary gland.
MINOR MESH HEADINGS: Disease-Models,-Animal; Genes,-Homeobox; Homeodomain-Proteins-genetics; Homeodomain-Proteins-physiology; Hypopituitarism-embryology; Hypopituitarism-genetics; Hypopituitarism-physiopathology; Mice-; Mice,-Mutant-Strains; Phenotype-; Pituitary-Gland-physiology; Transcription-Factors-genetics
MAJOR MeSH HEADINGS: *Pituitary-Gland-embryology; *Transcription-Factors-physiology
CHECKTAGS: Animal; Human; Support,-Non-U.S.-Gov't
PUBLICATION TYPE: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
CAS REGISTRY NUMBER OR EC NUMBER: 0; 0; 0; 0; 0; 149348-15-2; 184787-43-7
NAME OF SUBSTANCE: Homeodomain-Proteins; Ptx1-protein; POU1F1-protein; PROP1-protein; Transcription-Factors; HES-1-protein; Rieg-protein
MEDLINE ACCESSION NUMBER: 20017065
UPDATE CODE: 200002
Record 7 of 11 in MEDLINE EXPRESS (R) 2000/01-2000/09
TITLE: Normal growth despite GH, IGF-I and IGF-II deficiency.
AUTHOR(S): Hathout-EH; Baylink-DJ; Mohan-S
ADDRESS OF AUTHOR: Loma Linda University Children's Hospital and School of Medicine and Jerry L Pettis VA Medical Center, Loma Linda, CA, USA.
SOURCE (BIBLIOGRAPHIC CITATION): Growth-Horm-IGF-Res. 1999 Aug; 9(4): 272-7
INTERNATIONAL STANDARD SERIAL NUMBER: 1096-6374
PUBLICATION YEAR: 1999
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: SCOTLAND
ABSTRACT: A 6.5-year-old male with normal linear growth, despite septo-optic dysplasia, panhypopituitarism and a deficient GH/IGF axis, is presented. In addition to measuring IGF-I, IGF-II and IGFBP-3, serum IGFBP-1, -2, -4 and -5 were measured. A human osteosarcoma cell line was used to assess growth-promoting activity in the patient's serum. The role of leptin in linear growth in this case was investigated. There was no evidence for hyperinsulinism or hyperandrogenism. GH was undetectable upon multiple stimulation. GHBP was elevated. Serum IGF-I (25 &mgr;g/l), IGF-II (194 &mgr;g/l), IGFBP-3 (0.4 mg/l), and IGFBP-5 (87 &mgr;g/l) levels were low compared to age-matched prepubertal children. Serum IGFBP-4 level was normal. Molecular size of IGF-II in the patient's serum was normal, suggesting normal IGF-II bioavailability. Human osteosarcoma cell proliferation in response to the patient's serum was similar to sera from age-matched normal controls. Leptin levels were markedly elevated. Osteoblast cell proliferation was not stimulated by leptin. The data demonstrate that normal growth and osteoblast cell proliferation in this patient is not mediated by GH, total IGFs, insulin, or leptin, and suggest the presence of a yet unidentified growth factor or mechanism. The case offers a detailed picture of binding proteins in a case of growth without GH. It introduces osteoblast cell proliferation as a method of assessing serum growth-promoting activity in such cases. It adds IGF-II and leptin to the list of excluded growth-promoting candidates in GH-independent growth, and further demonstrates our incomplete understanding of the phenomenon of growth. Copyright 1999 Harcourt Publishers Ltd.
MINOR MESH HEADINGS: Child-; Hydrocortisone-metabolism; Hydrocortisone-therapeutic-use; Hypoglycemia-complications; Hypothyroidism-complications; Immune-Sera; Insulin-Like-Growth-Factor-Binding-Protein-3-blood; Insulin-Like-Growth-Factor-I-drug-effects; Insulin-Like-Growth-Factor-II-drug-effects; Karyotyping-; Leptin-blood; Levothyroxine-therapeutic-use; Somatropin-blood; Vision-Disorders-complications; Vision-Disorders-diagnosis
MAJOR MeSH HEADINGS: *Body-Height; *Insulin-Like-Growth-Factor-I-deficiency; *Insulin-Like-Growth-Factor-II-deficiency; *Somatropin-deficiency
CHECKTAGS: Case-Report; Human; Male
PUBLICATION TYPE: JOURNAL-ARTICLE
CAS REGISTRY NUMBER OR EC NUMBER: 0; 0; 0; 12629-01-5; 50-23-7; 51-48-9; 67763-96-6; 67763-97-7
NAME OF SUBSTANCE: Immune-Sera; Insulin-Like-Growth-Factor-Binding-Protein-3; Leptin; Somatropin; Hydrocortisone; Levothyroxine; Insulin-Like-Growth-Factor-I; Insulin-Like-Growth-Factor-II
MEDLINE ACCESSION NUMBER: 99444072
UPDATE CODE: 200002
Record 8 of 11 in MEDLINE EXPRESS (R) 1997-1999
TITLE: Optic nerve morphology may reveal adverse events during prenatal and perinatal life--digital image analysis.
AUTHOR(S): Hellstrom-A
ADDRESS OF AUTHOR: Department of Ophthalmology, Institute of Clinical Neuroscience, Sahlgrenska University Hospital/East, Goteborg, Sweden.
SOURCE (BIBLIOGRAPHIC CITATION): Surv-Ophthalmol. 1999 Oct; 44 Suppl 1: S63-73
INTERNATIONAL STANDARD SERIAL NUMBER: 0039-6257
PUBLICATION YEAR: 1999
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: OBJECTIVE: To evaluate optic nerve morphology in children with various conditions caused by adverse events during prenatal and/or perinatal life and to investigate whether optic nerve morphology can reveal brain lesions associated with these conditions, as well as provide insight into the etiology and timing of the prenatal and perinatal damage. METHODS AND PATIENTS: A digital image analysis technique was used to analyze fundus photographs. One hundred healthy Swedish individuals of various ages from childhood to adolescence constituted a reference group. The following patient groups were chosen to represent various clinical conditions affecting the newborn or fetus at different stages of development: children born preterm (N = 39), children with fetal alcohol syndrome (FAS [N = 16]), children with periventricular leukomalacia (PVL [N = 17]), and children with septo-optic dysplasia (SOD [N = 6]). RESULTS: Preterm children without known brain lesions demonstrated normal optic disk morphology but abnormal retinal vascular pattern; children born preterm with an acquired brain lesion late in gestation (PVL) demonstrated normal disk size with enlarged cups in addition to the abnormal vascular pattern. Children with prenatal alcohol exposure (FAS) had a subnormal optic disk area with increased tortuosity of both arteries and veins, whereas children born at term with an early acquired brain lesion (SOD) had a markedly reduced optic disk area with isolated tortuosity of the retinal veins. CONCLUSIONS: Evaluation of optic nerve morphology, by digital image analysis, demonstrated that differences in ocular fundus morphology were correlated with differences in etiology and timing of the adverse event occurring in prenatal and perinatal life. In addition, digital image analysis may be a helpful tool for understanding variations in optic nerve and retinal vessel morphology and their relationship with central nervous pathology.
MINOR MESH HEADINGS: Adolescence-; Adult-; Child-; Child,-Preschool; Fetal-Alcohol-Syndrome-pathology; Fundus-Oculi; Infant,-Newborn; Infant,-Premature; Leukomalacia,-Periventricular-pathology; Optic-Nerve-abnormalities; Pituitary-Hormones-deficiency; Retinal-Vessels-pathology
MAJOR MeSH HEADINGS: *Fetal-Diseases-pathology; *Image-Processing,-Computer-Assisted; *Infant,-Newborn,-Diseases-pathology; *Optic-Nerve-pathology
CHECKTAGS: Female; Human; Male; Support,-Non-U.S.-Gov't
PUBLICATION TYPE: JOURNAL-ARTICLE
CAS REGISTRY NUMBER OR EC NUMBER: 0
NAME OF SUBSTANCE: Pituitary-Hormones
MEDLINE ACCESSION NUMBER: 20014154
UPDATE CODE: 200001
Record 9 of 11 in MEDLINE EXPRESS (R) 1997-1999
TITLE: The clinical and morphologic spectrum of optic nerve hypoplasia.
AUTHOR(S): Hellstrom-A; Wiklund-LM; Svensson-E
ADDRESS OF AUTHOR: Department of Clinical Neurosciences, University of Goteborg, Sweden. ann.hellstrom@medfak.gu.se
SOURCE (BIBLIOGRAPHIC CITATION): J-Aapos. 1999 Aug; 3(4): 212-20
INTERNATIONAL STANDARD SERIAL NUMBER: 1091-8531
PUBLICATION YEAR: 1999
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: UNITED-STATES
ABSTRACT: PURPOSE: The purpose of this study was to characterize the clinical and morphologic spectrum of all children referred for optic nerve hypoplasia to a tertiary referral hospital in Sweden during a 9-year period. SUBJECTS AND METHODS: A retrospective review was undertaken of the charts of 117 children (age range, 0.25-16 years), treated at the Children's Hospital, Goteberg between 1988 and 1996, after the diagnosis of optic nerve hypoplasia. Ocular fundus morphologic condition was evaluated by digital image analysis of fundus photographs in 50 children, and neuroimaging was performed in 57 children. RESULTS: Of the 117 children with optic nerve hypoplasia, 66 (56%) were boys and 51 (44%) were girls. Preterm birth occurred in 24 (20%), and 14 (12%) were born small for gestational age. Additional diagnoses, such as fetal alcohol syndrome, septo-optic dysplasia, perinatal adverse events, and neuropsychiatric disorders, were made in 88%; 7% had unilateral optic nerve hypoplasia. Most of the children had small optic disc, cup, and neuroretinal rim areas, as well as retinal vascular abnormalities; 75% were visually impaired, and a high incidence of nystagmus and strabismus was found among these children. CONCLUSION: This study indicates that optic nerve hypoplasia has a wide clinical and morphologic spectrum and is associated with a broad range of disorders of the central nervous system. It is suggested that differences in the etiology and timing of the lesion as well as associated lesions may explain this spectrum of optic nerve hypoplasia in children.
MINOR MESH HEADINGS: Adolescence-; Child-; Child,-Preschool; Image-Processing,-Computer-Assisted; Incidence-; Infant-; Ocular-Motility-Disorders-diagnosis; Ophthalmoscopy-; Optic-Nerve-pathology; Optic-Nerve-Diseases-diagnosis; Retinal-Vessels-abnormalities; Retrospective-Studies; Vision-Disorders-diagnosis; Visual-Acuity
MAJOR MeSH HEADINGS: *Ocular-Motility-Disorders-etiology; *Optic-Disk-pathology; *Optic-Nerve-abnormalities; *Optic-Nerve-Diseases-complications; *Vision-Disorders-etiology
CHECKTAGS: Comparative-Study; Female; Human; Male; Support,-Non-U.S.-Gov't
PUBLICATION TYPE: JOURNAL-ARTICLE
MEDLINE ACCESSION NUMBER: 99404873
UPDATE CODE: 199912
Record 10 of 11 in MEDLINE EXPRESS (R) 1997-1999
TITLE: Pituitary dysfunction, morbidity and mortality with congenital midline malformation of the cerebrum.
AUTHOR(S): Cameron-FJ; Khadilkar-VV; Stanhope-R
ADDRESS OF AUTHOR: Department of Endocrinology, Great Ormond Street Hospital for Sick Children NHS Trust. cameronf@cryptic.rch.unimelb.edu.au
SOURCE (BIBLIOGRAPHIC CITATION): Eur-J-Pediatr. 1999 Feb; 158(2): 97-102
INTERNATIONAL STANDARD SERIAL NUMBER: 0340-6199
PUBLICATION YEAR: 1999
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: GERMANY
ABSTRACT: The purpose of this study was to review systematically a series of patients with congenital midline brain defects and pituitary dysfunction in early childhood and to quantitate the degree of dysfunction and clinical outcome. This study was a retrospective analysis of case notes of patients with pituitary dysfunction associated with either a midline cerebral anomaly and/or optic nerve hypoplasia. Forty patients were studied: 2 with semilobar holoprosencephaly, 2 with lobar holoprosencephaly, 18 with septo-optic dysplasia with an intact septum pellucidum, 7 with septo-optic dysplasia with an absent septum pellucidum, 7 with agenesis of the corpus callosum and 4 patients with isolated pituitary hypoplasia. An early age of diagnosis, feeding difficulties, neurodevelopmental disability, visual impairment and seizures were common occurrences. Despite disordered neuro-anatomy, most seizure disorders were caused by hypoglycaemia or hypernatraemia. Hypotensive/hypoglycaemic crises accounted for two out of three deaths within the study population. Most of patients had multiple pituitary hormone deficiency with growth hormone and adrenocorticotrophic hormone deficiency occurring most commonly. Unequivocal isolated hypothalamic dysfunction was an uncommon finding. In congenital midline brain malformation there is a spectrum of disordered neuro-anatomy associated with variable pituitary dysfunction. Clinical manifestations such as convulsions and developmental delay may be due to disordered metabolism and/or neuro-anatomy. CONCLUSION: Children with congenital midline brain defects frequently manifest convulsions, neurodevelopmental disability and poor growth due to disordered metabolism and/or neuro-anatomy. Treating clinicians must be aware of the complex, dynamic neurological and metabolic nature of these patients and their potential for early demise.
MINOR MESH HEADINGS: Abnormalities,-Multiple-blood; Abnormalities,-Multiple-physiopathology; Adolescence-; Child-; Child,-Preschool; Holoprosencephaly-blood; Holoprosencephaly-epidemiology; Holoprosencephaly-physiopathology; Hormones-blood; Hormones-deficiency; Hypopituitarism-blood; Hypopituitarism-epidemiology; Hypopituitarism-physiopathology; Infant-; Infant,-Newborn; Retrospective-Studies
MAJOR MeSH HEADINGS: *Abnormalities,-Multiple-epidemiology; *Brain-abnormalities; *Hypopituitarism-congenital; *Pituitary-Gland-physiopathology
CHECKTAGS: Female; Human; Male
PUBLICATION TYPE: JOURNAL-ARTICLE
CAS REGISTRY NUMBER OR EC NUMBER: 0
NAME OF SUBSTANCE: Hormones
MEDLINE ACCESSION NUMBER: 99156390
UPDATE CODE: 199906
Record 11 of 11 in MEDLINE EXPRESS (R) 1997-1999
TITLE: Why is the retention of gonadotrophin secretion common in children with panhypopituitarism due to septo-optic dysplasia?
AUTHOR(S): Nanduri-VR; Stanhope-R
ADDRESS OF AUTHOR: Great Ormond Street Hospital for Children NHS Trust, London, UK.
SOURCE (BIBLIOGRAPHIC CITATION): Eur-J-Endocrinol. 1999 Jan; 140(1): 48-50
INTERNATIONAL STANDARD SERIAL NUMBER: 0804-4643
PUBLICATION YEAR: 1999
LANGUAGE OF ARTICLE: ENGLISH
COUNTRY OF PUBLICATION: ENGLAND
ABSTRACT: Septo-optic dysplasia (De Morsier syndrome) is a developmental anomaly of mid-line brain structures and includes optic nerve hypoplasia, absence of the septum pellucidum and hypothalamo-pituitary abnormalities. We describe seven patients (four female, three male) who had at least two out of the three features necessary for the diagnosis of septo-optic dysplasia. Four patients had hypopituitarism and yet normal gonadotrophin secretion: one of these also had anti-diuretic hormone insufficiency; three had isolated GH deficiency and yet had premature puberty, with the onset of puberty at least a year earlier than would have been expected for their bone age. In any progressive and evolving anterior pituitary lesion it is extremely unusual to lose corticotrophin-releasing hormone/ACTH and TRH/TSH secretion and yet to retain gonadotrophin secretion. GnRH neurons develop in the nasal mucosa and migrate to the hypothalamus in early fetal life. We hypothesise that the arrival of GnRH neurons in the hypothalamus after the development of a midline hypothalamic defect may explain these phenomena. Progress in spontaneous/premature puberty in children with De Morsier syndrome may have important implications for management. The combination of GH deficiency and premature puberty may allow an apparently normal growth rate but with an inappropriately advanced bone age resulting in impaired final stature. GnRH analogues may be a therapeutic option. In conclusion, some patients with De Morsier syndrome appear to retain the ability to secrete gonadotrophins in the face of loss of other hypothalamic releasing factors. The migration of GnRH neurons after the development of the midline defect may be an explanation.
MINOR MESH HEADINGS: Child-; Child,-Preschool; Hypopituitarism-etiology; Hypopituitarism-genetics; Infant-; Infant,-Newborn; Somatotropin-deficiency; Vasopressins-deficiency
MAJOR MeSH HEADINGS: *Gonadotropins-secretion; *Hypopituitarism-metabolism; *Optic-Nerve-abnormalities; *Septum-Pellucidum-abnormalities; *Syndrome-
CHECKTAGS: Female; Human; Male; Support,-Non-U.S.-Gov't
PUBLICATION TYPE: JOURNAL-ARTICLE
CAS REGISTRY NUMBER OR EC NUMBER: 0; 0; 9002-72-6
NAME OF SUBSTANCE: Gonadotropins; Vasopressins; Somatotropin
MEDLINE ACCESSION NUMBER: 99154855
UPDATE CODE: 199905