hrp0092p1-153 | Thyroid | ESPE2019

Homozygous c.2422delT hTPO Mutation in Three Patients with Congenital Hypothyroidism Followed Over 20 Years

Stoeva Iva , Mihova Kalina , Kaneva Radka

The homozygous deletion c.2422delT in the carboxyl-terminal coding region of the hTPO gene results in a frameshift mutation and leads to an early stop codon in exon 14 of the gene (p.Cys808AlafsX24). Combination with double heterozygous DUOX2 mutations was also reported. We present the data on the clinical course of CH in three patients with permanent congenital hypothyroidism (CH) harboring one and the same mutation. Pat1 was followed 29 yrs; after an uneventful pregnancy (no...

hrp0084p1-160 | Miscelleaneous | ESPE2015

Septo-Optic Dysplasia Associated with Koolen-de Vries Syndrome: A Case Report

Aroyo Ani , Stoeva Iva , Stancheva Gergana , Koleva Reni , Kaneva Radka

Background: Septo-optic dysplasia (SOD) is a rare congenital anomaly, clinically heterogeneous, combining optic nerve and pituitary gland hypoplasia, midline abnormalities of the brain, including absence of the corpus callosum and septum pellucidum. The diagnosis is made when two or more features of the classic triad are present. HESX1, SOX2, SOX3, FGF8, FGFR1, PROKR1, SHH, are implicated in the etiology of SOD.Objective and hypotheses: Description of a ...

hrp0084p3-1099 | Pituitary | ESPE2015

Isolated GH Deficiency (IGHD) Associated with 7q11.23 Duplication Syndrome: a Case Report

Aroyo Ani , Stoeva Iva , Stancheva Gergana , Avdshieva Daniela , Kaneva Radka

Background: Congenital pituitary hormone deficiency is etiologically heterogeneous and occurs in 1:4000 live births. Of those, isolated GH deficiency (IGHD) is the most common, followed by combined pituitary hormone deficiency with or without extrapituitary anomalies.Objective and hypotheses: Description of a patient with IGHD, associated with multiple additional organ anomalies.Method: Case report, Sequencing of HESX1, SOX2</e...

hrp0084p3-1193 | Thyroid | ESPE2015

NKX2-1 p.Asp266Argfs142X De Novo Mutation in a Girl with Congenital Hypothyroidism (CH): Phenotypic Description

Stoeva Iva , Thorwarth Anne , Stoilov Boris , Krude Heiko

Background: Ttf1−/− mice had complete absence of follicular and parafollicular cells, agenesis of lung parenchyma, ventral forebrain, and pituitary. Congenital hypothyroidism (CH) patients with chromosomal deletions encompassing the TTF1 locus and point mutations in the TTF1 gene confirmed its implication in the phenotype: CH with a thyroid gland in place, associated with respiratory distress syndro...

hrp0089p3-p015 | Adrenals and HPA Axis P3 | ESPE2018

A Homozygous Mutation c.518T>A (p.lle173Asn) of the CYP21A2 Gene Presenting as Non-Classical Congenital Adrenal Hyperplasia (NCAH)

Karamfilova Teodora , Stoeva Iva , Mihova Kalina , Kaneva Rada , Tsochev Kaloyan , Iotova Violeta

Congenital adrenal hyperplasia due to P450c21 (21-hydroxylase) deficiency is an autosomal recessive disorder presenting as three phenotypes dependent on the residual enzyme activity: two classical ones (salt wasting and simple virilizing, SV) and the milder NCAH. All forms have increased adrenal androgens. Around 0.1% of Caucasians and up to several percent of certain ethnic groups are affected by NCAH. Most NCAH patients remain undiagnosed. Symptoms of NCAH may develop at any...

hrp0089p1-p257 | Thyroid P1 | ESPE2018

Results of the hTPO Mutational Screening in Bulgarian Patients with Congenital Hypothyroidism (CH)

Stoeva Iva , Mihova Kalina , Stoilov Boris , Koleva Reni , Mladenov Wilhelm , Iotova Violeta , Kaneva Radka

Congenital hypothyroidism (CH) is a partial or complete loss of function of the thyroid gland resulting in absent or decreased synthesis and secretion of thyroid hormones affecting infants since birth. Mutations of the hTPO gene are associated with autosomal recessive forms of CH. Based on our TSH screening results, the number of children with eutopic primary CH is increasing. Molecular biology techniques can identify the CH genetic cause after selection based on family histor...

hrp0089p2-p388 | Thyroid P2 | ESPE2018

Clinical Course in a Girl with Two hTPO Mutations – Homozygous c.1268G>A (p.Gly393Arg) and Heterozygous c.208C>G (p.Ala70Pro): 27 Years of Follow Up

Stoeva Iva , Mihova Kalina , Koleva Reni , Zheliaskov Mitko , Stoilov Boris , Kaneva Radka

Of the several genetic defects responsible for thyroid dyshormonogenesis, mutations in TPO gene are the most prevalent causes of inherited defects in CH. Prevalent mutations are in exons 8-11 (catalytic site).Case presentation: Girl, born at 16d after term, before the introduction of the neonatal screening, with asphyxia, BL 55 cm, BW 4 kg. Because of insufficient weight gain, feeding difficulties, prolonged jaundice she was referred to a pediatric endoc...

hrp0086p2-p853 | Syndromes: Mechanisms and Management P2 | ESPE2016

A 3-year-old Boy with Growth Hormone Deficiency and Clinical Features of Ritscher–Schinzel Syndrome

Galcheva Sonya , Iotova Violeta , Bocheva Yana , Stoeva Iva , Tincheva Radka , Georgiev Radoslav , Marinov Lachezar

Ritscher-Schinzel (cranio-cerebello-cardiac, 3C) syndrome is a very rare recently delineated disorder with Dandy-Walker malformation, congenital heart defects and dysmorphic craniofacial features; however, the full spectrum of this disorder has not been determined.Objective and hypotheses: To present a patient with short stature and growth hormone (GH) deficiency as a part of the clinical manifestations of Ritscher-Schinzel syndrome.<p class="abstext...

hrp0082p3-d1-624 | Adrenals &amp; HP Axis | ESPE2014

Genotype–Phenotype Correlations in Bulgarian Patients with c.293-13A/C>G Splice Mutation of 21CYPA2 Picked up by Neonatal Screening (NS)

Stoeva Iva , Dineva Ganka , Kirov Andrey , Kostova Antoaneta , Todorov Tihomir , Aroyo Ani , Todorova Albena , Mitev Vanio

Background: Congenital adrenal hyperplasia (CAH) comprises a group of autosomal recessive disorders caused by defects in one of the several adrenal steroidogenic enzymes. 80–95% of CAH are due to mutations in CYP21A2 gene encoding 21 hydroxylase. Its residual activity defines the clinical form. Except deletions and large gene conversions, nine pseudogene-derived mutations are responsible for 95% of all CAH alleles. The mutational distribution varies between diffe...

hrp0082p3-d1-626 | Adrenals &amp; HP Axis | ESPE2014

Cyp21a2 Mutation Spectrum in Bulgarian Cah Patients

Todorova Albena , Kirov Andrey , Stoeva Iva , Todorov Tihomir , Dineva Ganka , Kostova Antoaneta , Aroyo Ani , Mitev Vanio

Background: Congenital adrenal hyperplasia (CAH) is a group of inborn errors of steroidogenesis. It is mainly caused by steroid 21-hydroxylase coding gene (CYP21A2) mutations. More than 30% of the CYP21A2 mutations are deletions, with ethnic specific differences. The Bulgarian mutational spectrum of CYP21A2 gene is unknown.Objective and hypotheses: To determine CYP21A2 mutation spectrum in Bulgarian CAH patients.<p...