Population-based stroke screening days in the 12th district of Budapest in 2011 and 2016 - What have and what have not changed?

BACKGROUND AND PURPOSE: Population-based screening is an option to identify persons at high risk for stroke. However it is associated with rather high expenses, necessitating the selection of effective methods that take local characteristics into account. The 12th district of Budapest has a long tradition of population-based screening for frequent and preventable diseases. The Szent János Hospital hosts an annual stroke screening day. In the present study, previously published data from the 2011 screening were compared with those obtained in 2016, looking for changes and tendencies throughout the examined period. METHODS: The screening day was conducted in a generally similar way in 2011 and 2016. Similarly to the previous event, the program was organized on a Saturday, the call for the event was spread by the local newspaper. The crew composition was the same. As regards the components of the screening (currently including general history taking, risk status assessment, blood pressure measurement, BMI assessment, cholesterol and blood glucose tests, carotid duplex ultrasonography, and ophthalmological examination), the only difference was the absence of cardiologic examination (it was conducted on an independent day). The anonymous data sheet was the same. RESULTS: The number of participants in the 2016 event was 33, to provide more comfortable conditions. The female predominance was slightly less pronounced but was still present in 2016 (60.6% vs. 72.9%). The mean age became substantially higher (71.2 y vs. 62.9 y). The ratios of participants with higher level of education (97% vs. 94%) and those who are married were still remarkable. The most frequent risk factors were the same; however the ratio of participants with hypertension, 'other heart disease', and diabetes increased, whereas that of with hyperlipidemia and obesity decreased. The incidence of atrial fibrillation was unaltered. None of the participants in 2016 admitted smoking (previously this ratio was 20.8%) or drinking heavily. The findings of the carotid ultrasonography revealed a more favorable vascular status. Ophthalmological assessments (predominantly hypertensive alterations on fundoscopy) revealed that the pathological vs. physiological ratio switched to 1:2 from 2:1. The final evaluation of the screening program likewise demonstrated an improved overall state of health of the population. CONCLUSION: We observed a more favorable stroke risk status of the population in 2016. Whether it is indeed a tendency unknown at present. The role of the local media in calling for screening is still decisive, and the cohesive power of the family is important.

Clinical and genetic characteristics of craniosynostosis in Hungary.

Craniosynostosis, the premature closure of cranial sutures, is a common craniofacial disorder with heterogeneous etiology and appearance. The purpose of this study was to investigate the clinical and molecular characteristics of craniosynostoses in Hungary, including the classification of patients and the genetic analysis of the syndromic forms. Between 2006 and 2012, 200 patients with craniosynostosis were studied. Classification was based on the suture(s) involved and the associated clinical features. In syndromic cases, genetic analyses, including mutational screening of the hotspot regions of the FGFR1, FGFR2, FGFR3, and TWIST1 genes, karyotyping and FISH study of TWIST1, were performed. The majority (88%) of all patients with craniosynostosis were nonsyndromic. The sagittal suture was most commonly involved, followed by the coronal, metopic, and lambdoid sutures. Male, twin gestation, and very low birth weight were risk factors for craniosynostosis. Syndromic craniosynostosis was detected in 24 patients. In 17 of these patients, Apert, Crouzon, Pfeiffer, Muenke, or Saethre-Chotzen syndromes were identified. In one patient, multiple-suture craniosynostosis was associated with achondroplasia. Clinical signs were not typical for any particular syndrome in six patients. Genetic abnormalities were detected in 18 syndromic patients and in 8 relatives. In addition to 10 different, known mutations in FGFR1,FGFR2 or FGFR3, one novel missense mutation, c.528C>G(p.Ser176Arg), was detected in the TWIST1 gene of a patient with Saethre-Chotzen syndrome. Our results indicate that detailed clinical assessment is of paramount importance in the classification of patients and allows indication of targeted molecular testing with the highest possible diagnostic yield.

[Results of clinical and genetic diagnosis of rare diseases in the Eastern region of Hungary (2007-2013)]. / Ritka genetikai betegségek klinikai és genetikai diagnosztikájában szerzett tapasztalataink a kelet-magyarországi régióban (2007-2013).

INTRODUCTION: 80% of rare diseases have a genetic origin, and 50% manifest themselves as congenital anomalies. Their adequate health care includes early recognition of genetic anomalies and prevention of recurrence. AIM: The aims of the authors were to provide correct diagnoses to patients with multiple congenital anomalies with or without mental retardation attending to the outpatient clinic of the Clinical Genetics Center at the University of Debrecen in the time interval between August 1, 2007 and March 31, 2013, establish the possibility of prenatal diagnosis, assess the distribution of different genetic mechanisms in the background of rare genetic diseases, compare them with international data, and develop an algorithm for the diagnostic approach of rare genetic diseases applicable in Hungary. METHOD: Clinical data and genetic results of patients were evaluated, and patients were categorized into one of the ten proposed etiological groups, based on which the distribution of genetic causes was defined. RESULTS: Clinical diagnosis was achieved in 64.3% of patients, confirmed genetic diagnosis in 37.8%, while 35.7% of patients remained undiagnosed. Several dysmorphic syndromes and metabolic disorders were first diagnosed in Hungary, two of which unique in the literature. CONCLUSIONS: In the centre of the authors the diagnostic effectiveness of chromosome aberrations exceeds the international standards, that of known microdeletions and dysmorphic syndromes meets international data, and the genetic diagnosis of mendelian disorders and submicroscopic copy number changes remain below international figures.

[Deletion 15q26 syndrome]. / 15q26-microdeletio-szindróma.

The association of short stature, microcephaly, congenital cardiac anomaly and intellectual deficit should always raise the suspicion of chromosomal etiology. If G-banded karyotyping fails to detect large chromosomal aberrations, array comparative genomic hybridization (array CGH) should be performed to screen for submicroscopic pathological copy number changes. The authors present a six-year-old girl whose symptoms arose from a 4.1 Mb loss in the 15q26.2-26.3 telomeric region. The syndrome is characterized by a resistance to the insulin-like growth factor 1 - in our case the increased level of the insulin-like growth factor 1 together with the persistent longitudinal growth failure was an important finding and differential diagnostic feature. A brief overview of the literature is provided.

Achondroplasia with multiple-suture craniosynostosis: a report of a new case of this rare association.

We report on a female patient with an exceedingly rare combination of achondroplasia and multiple-suture craniosynostosis. Besides the specific features of achondroplasia, synostosis of the metopic, coronal, lambdoid, and squamosal sutures was found. Series of neurosurgical interventions were carried out, principally for acrocephaly and posterior plagiocephaly. The most common achondroplasia mutation, a p.Gly380Arg in the fibroblast growth factor receptor 3 (FGFR3) gene, was detected. Cytogenetic and array CGH analyses, as well as molecular genetic testing of FGFR1, 2, 3 and TWIST1 genes failed to identify any additional genetic alteration. It is suggested that this unusual phenotype is a result of variable expressivity of the common achondroplasia mutation.

[Citogenetic and molecular genetic studies in infertility in eastern Hungary]. / Infertilitásban végzett citogenetikai és molekuláris genetikai vizsgálatok a kelet-magyarországi régióban.

INTRODUCTION: In developed countries 10-15% of the couples are affected by infertility. In half of them genetic factors can be identified. AIMS: We studied genetic alterations in infertility in Hungarian patients. METHODS: Cyogenetic analyses were performed in 195 females and 305 males. In 17 females FMR1 mutations, in 150 males Y microdeletions, and aneuploidy were studied in the sperm of 28 males. In a carrier male sperm meiotic segregation was studied. RESULTS: The most common aberrations in females were X chromosome aneuploidia and inversion (3.6%), while the same in males Klinefelter-syndrome (3.3%) and autosomal translocations (2%). In two females FMR1 premutation was found. While Y microdeletions were identified only in azoospermic and severe oligozoospermic men, partial microdeletions could also be detected in normozoospermic males. A higher aberration rate was found in cases with abnormality in both the number and motility of sperm. In a male patient with 46,XY,t(3;6)(q21;q23) karyotype, 53.2% of spem carried unbalanced chromosome assortment. CONCLUSIONS: Knowledge of abnormalities may help in genetic counseling and choosing the most effective reproduction technique.

Subtelomeric 6.7 Mb trisomy 10p and 5.6 Mb monosomy 21q detected by FISH and array-CGH in three related patients.

Cryptic subtelomeric chromosomal aberrations are responsible for 5-10% of moderate/severe and 1% of mild intellectual disability. Unbalanced subtelomeric chromosomal rearrangements result in variable phenotypes which seem to be highly influenced by both the size of the duplication/deletion and the chromosomes involved in the translocation. We report on three related patients with moderate intellectual disability, language delay, hypotonia, facial dysmorphism, cardiac anomalies, scoliosis, and kyphosis in whom a familial (maternal) unbalanced submicroscopic translocation was found by subtelomeric fluorescence in situ hybridization (FISH). This rearrangement resulted in a partial trisomy 10pter and partial monosomy 21qter. The karyotype was 46,XY.ish der(21)t(10;21)(p14;q22.2). Confirmation of a 6.7 Mb size distal duplication of the p15.3-14 region of chromosome 10 and a 5.6 Mb distal deletion of the q22.2-22.3 region of chromosome 21 was obtained by array-CGH. To our best knowledge, such a composition of subtelomeric unbalanced translocations has not yet been published. Detection of this aberration in successive pregnancies of carrier members of the family by prenatal FISH could prevent the recurrence of the disease. Furthermore, detection of the rearrangements and identification of genes located in the chromosomal regions involved might be of interest.

Correlation study between sperm concentration, hyaluronic acid-binding capacity and sperm aneuploidy in Hungarian patients.

Infertile men with low sperm concentration and/or less motile spermatozoa have an increased risk of producing aneuploid spermatozoa. Selecting spermatozoa by hyaluronic acid (HA) binding may reduce genetic risks such as chromosomal rearrangements and numerical aberrations. Fluorescence in-situ hybridization (FISH) has been used to evaluate the presence of aneuploidies. This study examined spermatozoa of 10 oligozoospermic, 9 asthenozoospermic, 9 oligoasthenozoospermic and 17 normozoospermic men by HA binding and FISH. Mean percentage of HA-bound spermatozoa in the normozoospermic group was 81%, which was significantly higher than in the oligozoospermic (P<0.001), asthenozoospermic (P<0.001) and oligoasthenozoospermic (P<0.001) groups. Disomy of sex chromosomes (P=0.014) and chromosome 17 (P=0.0019), diploidy (P=0.03) and estimated numerical chromosome aberrations (P=0.004) were significantly higher in the oligoasthenozoospermic group compared with the other groups. There were statistically significant relationships (P<0.001) between sperm concentration and HA binding (r=0.658), between sperm concentration and estimated numerical chromosome aberrations (r=-0.668) and between HA binding and estimated numerical chromosome aberrations (r=-0.682). HA binding and aneuploidy studies of spermatozoa in individual cases allow prediction of reproductive prognosis and provision of appropriate genetic counselling. Infertile men with normal karyotypes and low sperm concentrations and/or less motile spermatozoa have significantly increased risks of producing aneuploid (diminished mature) spermatozoa. Selecting spermatozoa by hyaluronic acid (HA) binding, based on a binding between sperm receptors for zona pellucida and HA, may reduce the potential genetic risks such as chromosomal rearrangements and numerical aberrations. In the present study we examined sperm samples of 45 men with different sperm parameters by HA-binding assay and fluorescence in-situ hybridization (FISH). Mean percentage of HA-bound spermatozoa in the normozoospermic group was significantly higher than the oligozoospermic, the asthenozoospermic and the oligoasthenozoospermic groups. Using FISH, disomy of sex chromosomes and chromosome 17, diploidy and estimated numerical chromosome aberration frequencies were significantly higher in the oligoasthenozoospermic group compared with the three other groups. A significant positive correlation was found between the sperm concentration and the HA-binding capacity, and significant negative correlations between the sperm concentration and the estimated numerical chromosomes aberrations as well as between the HA-binding ability and the estimated numerical chromosome aberrations were identified. We conclude that HA-binding assay and sperm aneuploidy study using FISH may help to predict the reproductive ability of selected infertile male patients and to provide appropriate genetic counselling.

[Dysgenetic male pseudohermaphroditism]. / Dysgeneticus pseudohermaphroditismus masculinus.

The authors report a case of a dysgenetic male pseudohermaphroditism with a 45,X/46,XY karyotype in a mosaic form, which was diagnosed in an infant. The one-week-old infant was evaluated because of proximal hypospadias and retention of the right testis. The results of hormonal tests were the followings: serum FSH 5.2 mU/ml; LH: 2.0 mU/ml; testosterone: 144.3 ng/dl; androstendione: 0.42 µg/l; 17-hydroxyprogesterone: 1.12 ng/ml. Chromosomal analysis revealed 45,X/46,XY karyotype. Fluorescent in vitro hybridization showed that 51% of the lymphocytes had the Y chromosome and the SRY gene. Analysis of the SRY showed no deletion in the AZF a,b,c regions. Pelvic magnetic resonance imaging indicated the presence of vagina between the bladder and the rectum, and it showed a mass measuring 15×8 mm in the right inguinal canal as well as an oval gonadal mass with a size of 13×7 mm in the left scrotum. During surgical intervention, performed at the age of one, the right gonad was removed and biopsy of the scrotal testis was performed. Histological examination revealed dysgenetic testis in both sides. The authors emphasize the necessity of cytogenetic and endocrinological investigations of newborns with perineoscrotal hypospadia and bilateral or unilateral maldescent testes immediately after birth. Surgical removal of the dysgenetic testicular tissue located in the abdominal cavity and its histological evaluation provides separation of mixed gonadal dysgenesis, dysgenetic male pseudohermaphroditism, bilateral gonadal dysgenesis and ovotestis in the 45,X/46,XY mosaic cases. An accurate evaluation is necessary for a correct sex assignment and for surgical intervention to prevent neoplastic degeneration of the dysgenetic gonad.

Blepharophimosis mental retardation syndrome Say-Barber/Biesecker/Young-Simpson type - new findings with neuroimaging.

We report on a female patient with blepharophimosis mental retardation syndrome of Say/Barber/Biesecker/Young-Simpson (SBBYS) type. Main findings in her were marked developmental delay, blepharophimosis, ptosis, cleft palate, external auditory canal stenosis, small and malformed teeth, hypothyroidism, hearing impairment, and joint limitations. We performed diffusion tensor magnetic resonance imaging (MRI) and tractography of the brain which showed inappropriate myelination and disturbed white matter integrity. Cytogenetic analysis, subtelomeric fluorescence in situ hybridization and comparative genomic hybridization failed to identify an abnormality. It remains uncertain whether the MRI findings are specific to the present patient or form part of the SBBYS syndrome.

A patient with Smith-Lemli-Opitz syndrome: novel mutation of the DHCR7 gene and effects of therapy with simvastatin and cholesterol supplement.

BACKGROUND: The Smith-Lemli-Opitz (SLO) syndrome is a multiple congenital anomaly with mental retardation due to a decreased or lack of activity of 7-dehydrocholesterol reductase as a consequence of mutations of the DHCR7 gene. This paper describes a special patient with SLO syndrome. Laboratory examination showed low cholesterol (2.77 mmol/L) and increased 7-dehydrocholesterol level (102 mg/L). Molecular genetic analysis revealed a compound heterozygosity c.964-1G>C/p.G366V (c.G1370T) of the proband. The p.G366V is a novel mutation of the DHCR7 gene with guanine by thymine nucleotide exchange resulting in glycin by valin amino acid exchange in the dehydrocholesterol reductase enzyme. Simvastatin (0.2 mg/kg/day) and cholesterol replacement therapy (150-250 mg/kg/day) led to significant improvement in the patient's laboratory findings (7-dehydrocholesterol, cholesterol) as well as in his behavior and gross motor function. CONCLUSION: Our patient demonstrates that the c.964-1G>C/p.G366V (c.G1370T) genotype of combined heterozygosity is associated with a typical form of SLO syndrome along with moderately altered laboratory findings and a favorable biochemical response to cholesterol and simvastatin treatment.

[Detection of subtelomeric chromosomal rearrangements in idiopathic mental retardation]. / Szubtelomerikus kromoszómaátrendezodések kimutatása idiopathiás mentális retardációban.

Subtelomeric regions of chromosomes are rich in genes; their rearrangements cannot be identified by traditional chromosome analysis. Since these subtelomeric aberrations are responsible for about 7% of cases with mental retardation, their detection is important both from the diagnostic point of view and to prevent recurrence in the family. Subtelomeric chromosomal alterations can be detected by fluorescence in situ hybridization. Based on international criteria, 35 out of 59 patients with mental retardation have been selected. Subtelomeric rearrangements were revealed in 6 patients (5 familial cases, 1 new onset) whereas the subtelomeric FISH result was normal in 29 cases. Deletion of 8pter and duplication of 12pter were detected in 2 patients, while a deletion of 21qter and duplication of the 10pter due to an unbalanced translocation were found in 3 other cases. Finally, a new onset deletion of 3qter was observed in 1 patient. In order to clarify the origin of chromosome aberrations, 12 healthy family members were also examined, 5 of them carried balanced translocations. We concluded that the phenotype is mostly influenced by the size of regions involved in deletion/duplication and - in case of translocations - by the associated chromosomal abnormalities.

[Conductive education for children with neurological diseases]. / A konduktív nevelés gyermekneurológiai indiikációja.

Conductive education, developed by the 40-ies of the last century, spread around the world in spite the lack of hard scientific evidence for its benefit. There are types of cerebral palsy (athetosis, ataxia) in which conductive education might have the unique role to help. In cerebral palsy of other types it is much helpful if the disturbance of body scheme and degree of somatomotor neglect are superior to the palsy. Short-term results of conductive education are visible in the better movement coordination while the long-term outcome is the increased activities of daily living.

Pattern of increased cerebral FDG uptake in Down syndrome patients.

Resting cerebral glucose metabolism was assessed by 18[F]-fluorodeoxyglucose in 11 Down syndrome patients. Standardized uptake values were determined on a pixel-by-pixel basis from the measured tissue-activity data. The results revealed a mean overall 18[F]-fluorodeoxyglucose uptake in the Down syndrome patients close to that observed in the control group, consisting of children and young adults. However, the standard deviation of the standardized uptake values was much higher in the Down syndrome group in almost all voxels relating to the gray matter. The statistical parametric mapping method was applied to compare the cerebral 18[F]-fluorodeoxyglucose accumulation patterns of the Down syndrome and control groups. Six regions (clusters) were found for which the glucose uptake was higher in the Down syndrome patients than in the control group. The anatomic localization of these clusters was based on magnetic resonance investigations and a brain-atlas technique. The localization of the identified clusters with an increased glucose metabolism in the Down syndrome patients suggests that these subjects have an enhanced resting neuronal activity in cortical areas involved in reasoning, cognition, and speech as compared with normal subjects.

[Detection of trisomy 8 and monosomy 7 in chronic granulocytic leukemia and myelodysplastic syndrome by cytogenetic analysis and fluorescence in situ hybridization]. / A citogenetikai vizsgálat és fluoreszcencia in situ hibridizáció párhuzamos alkalmazásának jelentósége krónikus granulocytás leukaemiában és myelodysplasiás szindrómában a 8-as triszómia és a 7-es monoszómia kimutatására.

INTRODUCTION AND AIMS: In this retrospective study the authors studied how interphase fluorescence in situ hybridization can be applied to the diagnosis of numerical chromosomal anomalies failed to be identified by cytogenetic analysis. METHODS: Thirty-four patients, 27 with chronic granulocytic leukemia and seven with myelodysplastic syndrome, were studied in order to identify disease-specific aberrations, trisomy 8 and monosomy 7 using both traditional cytogenetic analysis and fluorescence in situ hybridization on interphase bone marrow cells. Using alphoid-satellite centromeric specific probes, trisomy 8 indicating the progression of the disease and poor prognosis in chronic granulocytic leukemia as well as monosomy 7 in myelodysplastic syndrome were identified. RESULTS: In 21 of 34 cases both methods led to the same results. In 13 patients fluorescence in situ hybridization making possible to examine a great number of cells, provided more information about the gain and loss of chromosomes above and clarified uncertain cytogenetic results. CONCLUSIONS: In both hematological malignancies, studied by the authors, fluorescence in situ hybridization proved a useful and sensitive method to determine chromosomes unrecognized or not accurately identified by the traditional cytogenetic analysis and to define the ratio of pathological cells. At the same time the results confirm that conventional cytogenetic analysis is still essential in diagnosing the genetic alterations of malignant cells and point at the chromosomes that are worth further studying by other methods.

[Cerebral glucose metabolism in Down syndrome using positron emission tomography]. / Az agyi glükózanyagcsere vizsgálata Down-kórban pozitronemissziós tomográfiával.

Resting cerebral glucose metabolism was assessed by PET using FDG in eleven Down syndrome (DS) patients. Standardized uptake values (SUV) were determined on a pixel by pixel basis from the measured tissue FDG-activity data. The results showed that the mean value of the global FDG-uptake in the DS patients was not significantly different from the one obtained in the control group consisting of children and young adults. The standard deviation of SUV, however, was much higher in the DS group in almost all regions. The statistical parametric mapping (SPM) method was applied to compare the relative cerebral FDG accumulation pattern of the populations. Six regions (clusters) were found in which the glucose-uptake was higher in the DS patients than in the control group. The anatomical localization of these clusters was based on MRI investigations and brain-atlas technique.

[Study of pathogenetic role of Epstein-Barr virus in Hungarian patients with B-cell non-Hodgkin lymphomas]. / Az Epstein-Barr vírus patogenetikai szerepének tanulmányozása magyarországi B-sejtes non-Hodgkin lymphomás betegekben.

INTRODUCTION: The Epstein-Barr virus is a member of herpesvirus family. It plays an important role in the etiopathogenesis of Burkitt lymphoma, other B-cell non-Hodgkin lymphomas, nasopharyngeal carcinoma, X chromosome-linked lymphoproliferative disease, Hodgkin lymphomas and a part of T-cell lymphomas. It has been suggested that association of Epstein-Barr virus with lymphomas and its pathological significance in disease varies in different geographical areas. The aim of our study was to reveal the role of Epstein-Barr virus in B-cell non-Hodgkin lymphomas diagnosed in Hungary. The authors asked: A) What is the frequency of the presence of virus genome in the biopsy specimen from B-cell non-Hodgkin patients? B) Which types of virus latency can be observed? PATIENTS AND METHODS: Genomic DNA and EBER-specific RNA of Epstein-Barr virus in paraffin-embedded specimens were detected by polymerase chain reaction and in situ hybridisation, respectively. RESULTS: Out of 36 B-cell non-Hodgkin lymphoma cases, 16 (45%) were found to be positive for Epstein-Barr virus by the above methods. Expression of latency genes, nuclear antigene-2 and latent membrane protein-1 was studied by immunohistochemical technique. The 16 virus-positive non-Hodgkin lymphoma cases showed Epstein-Barr virus latency types II. (37%) or III. (63%). CONCLUSIONS: The authors data suggest that Epstein-Barr virus may be associated with the development of B-cell non-Hodgkin lymphomas in Hungarian patients.

Lissencephaly and band heterotopia: LIS1, TUBA1A, and DCX mutations in Hungary.

The spectrum of lissencephaly ranges from absent (agyria) or decreased (pachygyria) convolutions to less severe malformation known as subcortical band heterotopia. Mutations involving LIS1 and TUBA1A result in the classic form of lissencephaly, whereas mutations of the DCX gene cause lissencephaly in males and subcortical band heterotopia in females. This report describes the clinical manifestations and imaging and genetic findings in 2 boys with lissencephaly and a girl with subcortical band heterotopia. An ovel mutation (c.83_84delAT, p.Tyr28Phefs*31) was identified in LIS1 in 1 of the boys with lissencephaly and another novel mutation (c.200delG, p.Ile68Leufs*87) was found in DCX in the girl with subcortical band heterotopia. The mutations appeared in the first half of the genes and are predicted to result in truncated proteins. A mutation was found in the TUBA1A gene (c.1205G>A, p.Arg402His) in the other boy. This mutation affects the folding of tubulin heterodimers, changing the interactions with proteins that bind microtubules.

Endocrine and anatomical findings in a case of Solitary Median Maxillary Central Incisor Syndrome.

Solitary Median Maxillary Central Incisor Syndrome (SMMCI) is a rare malformation syndrome consisting of multiple, mainly midline defects. Some authors suggest that it is a mild manifestation of the wide spectrum of holoprosencephaly, others classify it rather as a distinct entity. Authors report a case of SMMCI presenting with growth retardation, mild intellectual disability and absence of puberty. Cytogenetic and molecular cytogenetic investigations could identify no abnormalities. The presence of a single maxillary incisor called for further investigations to clarify hidden anomalies, these were empty sella, panhypopituitarism, hypothyroidism, and hypoplasia of the inner genitals. Based on the above findings, growth hormone, estrogen, and L-thyroxine substitution was introduced, which resulted in satisfactory longitudinal growth and onset of sexual maturation. We suggest genetic counselling and if needed, invasive investigations in female patients with short stature and absent/delayed puberty, with or without sex chromosomal anomalies, as the adequate therapy and even the quality of life of patient depends largely on the knowledge of their anatomical and endocrine status.

Meiotic segregation study of a novel t(3;6)(q21;q23) in an infertile man using fluorescence in situ hybridization (FISH).

Male carriers with balanced reciprocal translocations can produce a variable proportion of unbalanced gametes resulting in reproductive failures. The presence of a structural rearrangement may induce an interchromosomal effect. This is characterized by abnormal bivalents not involved in the reorganization thereby yielding non-disjunction, which would present as aneuploid spermatozoa for these chromosomes. In the present case report segregation analysis of the sperm and investigation of interchromosomal effect were carried out using cytogenetic and fluorescence in situ hybridization (FISH) analysis on blood lymphocytes. The karyotype of the patient was 46,XY,t(3;6)(q21;q23). During sperm segregation analysis a total of 2,002 sperms were evaluated, of which 46.8% showed normal/balanced (alternate segregation mode) and 53.2% of sperm showed an abnormal signal pattern. A significant difference in the frequency of the estimated number of chromosome anomalies was observed in the translocation carrier when compared to the normozoospermic group (P<0.0001) and the oligozoospermic group (P<0.0001). Meiotic segregation analysis of sperm together with aneuploidy assessment for X, Y, and 17 chromosomes using FISH allows for the determination of a reproductive prognosis in male balanced translocation carriers and can be used for appropriate genetic counseling.