Phenotypic variability in Patau syndrome.

UNLABELLED: Patau syndrome has an incidence of 1/10.000-20.000, the clinical diagnosis being suggested by the triad cleft lip and palate, microphthalmia/anophthalmia and postaxial polydactyly. Most frequent cytogenetic abnormality is free and homogeneous trisomy 13 (80.0%), rarely being detected trisomy mosaics or Robertsonian translocations. The objective of the study was to identify phenotypic features of trisomy 13. MATERIAL AND METHODS: The retrospective study was conducted on a trial group of 14 cases diagnosed cytogenetically with trisomy 13 between January 2000 and December 2012 at lasi Medical Genetics Centre. RESULTS: Of the 14 cases, 3 were evaluated pathologically (two aborted foetuses and one stillborn), 8 cases were detected in the neonatal period, and 3 in infancy. Clinical diagnosis was supported by the identification of a model of abnormal development, mainly characterized by: maxillary cleft (lip and palate--5 cases; lip--1 case), ocular abnormalities (microphthalmia/anophthalmia--7 cases; cyclopia--1 case), postaxial polydactyly (7 cases), scalp defects (6 cases), congenital heart anomalies (10 cases, 6 patients with atrial septal defect), complete holoprosencephaly (4 cases), ear abnormalities (11 cases), broad nasal root (10 cases). An important issue in confirming the phenotypic variability of Patau syndrome is that the classic clinical triad was identified only in one case. CONCLUSIONS: Patau syndrome is a disease with variable expression and is characterized by a pattern of abnormal prenatal development characterized by facial dysmorphia, polydactyly and severe birth defects (heart, brain) that generate an increased in utero and perinatal mortality.

Dicentric Chromosome 14;18 Plus Two Additional CNVs in a Girl with Microform Holoprosencephaly and Turner Stigmata.

We report a 20-year-old female with features evocative of Turner syndrome (short stature, broad trunk, mild webbed neck), dysmorphic face, minor features of holo-prosencephaly (HPE), small hands and feet, excessive hair growth on anterior trunk and intellectual disability. Cytogenetic analysis identified a pseudodicentric 14;18 chromosome. Genome wide single nucleotide polymorphism (SNP) array showed a terminal deletion of approximately 10.24 Mb, from 18p11.32 to 18p11.22, flanked by a duplication of approximately 1.15 Mb, from 18p11.22 to 18p11.21. In addition, the SNP array revealed a duplication of 516 kb in 16p11.2. We correlated the patient's clinical findings with the features mentioned in the literature for these copy number variations. This case study shows the importance of microarray analysis in the detection of cryptic chromosomal rearrangements in patients with intellectual disability and multiple congenital anomalies.

Ring autosomes: some unexpected findings.

Ring chromosomes are rare entities, usually associated with phenotypic abnormalities in correlation with the loss of genetic material. There are various breakpoints and sometimes there is a dynamic mosaicism that is reflected in clinical features. Most of the ring chromosomes are de novo occurrences. Our study reflects the experience of three Romanian cytogenetic laboratories in the field of ring chromosomes. We present six cases with ring chromosomes involving chromosomes 5, 13, 18, and 21. All ring chromosomes were identified after birth in children with plurimalformative syndromes. The ring chromosome was present in mosaic form in three cases, and this feature reflects the ring's instability. In case of ring chromosome 5, we report a possible association with oculo-auriculo-vertebral spectrum.

[Improvement of genetic diagnostic strategy in velo-cardio-facial syndrome]. / Optimizarea strategiei de diagnostic genetic în sindromul velo-cardio-facial.

UNLABELLED: Velo-Cardio-Facial Syndrome (VCFS) is characterized by congenital heart defects (CHD), palatal abnormalities, facial dysmorphism, neonatal hypocalcemia, immune deficit, speech and learning disabilities. SVCF is caused by microdeletion 22q11.2. Microdeletion is detected by fluorescence in situ hybridization (FISH). The highly variable phenotype makes diagnosis and selection for FISH more difficult. AIM: To retrospectively analyze and compare the phenotype of children with a clinical diagnosis of VCFS with/without 22q11 deletion; to verify the validity of literature guidelines and to describe combinations of clinical features that should lead to molecular analysis. MATERIAL AND METHODS: The present study was performed in 21 patients with a clinical diagnosis of VCFS. Methaphase chromosome spreads were prepared from phytohaemagglutinin stimulated lymphocyte culture by standard methods before FISH. The patients were divided into two groups according to FISH test: positive and negative. RESULTS: The features commonly noticed in FISH positive patients were: palatal abnormalities/hypernasal speech, learning disabilities, facial dysmorphism, tapered fingers (6/6), CHD (5/6) and recurrent infections (2/6). In FISH negative patients the following were found: learning disabilities, CHD (12/15); facial dysmorphism (10/15), family history of CHD (7/15), short stature (6/15), hypocalcemia, tapered fingers (5/15), recurrent infections (3/15) and palatal cleft (2/15). In both groups, Tobias and McDonald-McGinn guidelines were positive. CONCLUSIONS: VCFS has a highly variable phenotype. Our study suggests that 22q11.2 deletion analysis by FISH should be performed in patients who have at least 2 (newborn)/3 (child, adult) specific criteria: CHD, hypocalcemia, palatal abnormalities, facial dysmorphism, learning disabilities, digital anomalies, and immune deficit.

[Use of MLPA test in the detection of subtelomeric rearrangements--case report]. / Utilitatea testului MLPA in depistarea rearanjamentelor subtelomerice--discutii pe marginea unor cazuri de retard mintal idiopatic.

Genetic causes of mental retardation (MR) are heterogeneous, but subtelomeric rearrangements are an important one. MLPA technique provides the best results in case detection. We have used MLPA to identify subtelomeric rearrangements in children with idiopatic MR. The protocol included: clinical selection; karyotype; antiFMRP test; MLPA. We have selected cases using de Vries diagnostic score. Patient data were recorded in a database. The group was formed of 142 MR children. In 24 (16.9%) the karyotype was abnormal. 16 cases (11.3%) presented speech delay/autism, but antiFMRP test was normal. 60 MLPA tests were done: 46 cases (76.7% were normal, 6 (10%) abnormal, 4 (6.7%) had polymorphism and 4 (6.7%) could not be interpreted. Clinical features of the cases identified are illustrated. In conclusion, the diagnostic score is useful in case selection for further testing and MLPA proves to be efficient in diagnosing subtelomeric rearrangements as a possible cause of idiopatic MR.

[Idiopathic mental retardation--importance of clinical diagnostic scores for case selection]. / Retardul mental idiopatic--importanta scorurilor de diagnostic clinic pentru selectia cazurilor.

We present a retrospective study aimed to identify the correlation between de Vries clinical score and the detection of chromosomal abnormalities in mentally retarded (MR) children. We have used the score to identify patients who should be tested by karyotyping and subsequently MLPA (multiplex ligation dependent probe amplification) for subtelomeric rearrangements. Our group is formed of 36 children with variable MR associated with other anomalies. 18 children had chromosomal defects, whereas 18 had normal karyotypes. In the first group, total scores varied between 3 and 7. Chromosomal anomalies identified were: numerical (4) and structural (14). Chromosomes involved were: 1, 4, 5, 7, 8, 9, 17, X. Deletions were the most common and correlate with a greater score (> or = 4). Common clinical features were: short stature, microcephaly, nasal, ear and hand anomalies. In the second group the most frequent clinical feature was hand anomaly (61.2%) and cases with a high score have to be further tested (e.g. using MLPA) in order to identify minor defects. In our opinion a high score indicates the karyotype and then a MLPA testing. In conclusion, we present a retrospective study that proves the use of de Vries diagnostic score in the identification of chromosomal abnormalities in MR children.

[Clinical, epidemiological and cytogenetic studies on 221 patients with Down syndrome]. / Studii clinice, epidemiologice si citogenetice pe un lot de 221 pacienti cu sindrom Down.

UNLABELLED: Down syndrome, determined by 21 trisomy, represents a major cause of infantile morbidity and mortality. AIM: The analysis of dysmorphic features in Down syndrome, incidence of major congenital abnormalities, of some epidemiological parameters and cytogenetic specifics. MATERIAL AND METHOD: Methods used were clinical, epidemiological and cytogenetical. We analysed 221 patients, from Iasi county, with clinical supposition of Down syndrome, identified in the first year of life, between 1985 and 1999. RESULTS: The majority of patients (67%) have more than 5 from 10 characteristics dysmorphic signs of Down syndrome in neonatal period. Visceral congenital abnormalities--82 cases (37.1%) were isolate (cardiac or digestive) or multiple. The presence of one visceral abnormality determined the death of patient in 30 cases (46.15% of death). Medium incidence of Down syndrome in Iasi county was 1.306 per thousand (1/769 new-born), with median value 1.091per thousand and corrected value related to the maternal age 1.056 per thousand. Cytogenetic analysis was performed at 101 patients, in 95 cases (94.05%) clinical suspicion of Down syndrome was correct, patients presenting 21 trisomy (in the majority of cases a homogenous free trisomy). CONCLUSION: The data obtained by us are concordant with the majority of literature studies, that a test the correctness of clinical trial and validate our results.

[2 cases of Lowe syndrome]. / Doua cazuri de sindrom Löwe.

Löwe syndrome is a form of X-linked mental retardation with short stature, cataracts, renal tubular dysfunction and hypotonia. We present 2 cases to illustrate this rare entity, but also to discuss the suggestive aspect of the face and to underline the importance of molecular tests for genetic counselling. Both cases associate ocular, cerebral and renal defects. Molecular tests changed the recurrence risk in the first family.

[Goldenhar syndrome in adults]. / Sindromul Goldenhar la adult.

The paper presents the case of a 43 year old female patient with multi-malformations syndrome (facio-auriculo-vertebral syndrome), distinguished by alterations of the skeleton, face, sensorial organs and the heart. The syndrome is dominant at young ages and scarce at adults, and the explanation of the favorable evolution could be the lack of severe visceral or central nervous system involvement. The peculiar anomalies of this case are: asymmetric face, epibulbar dermoid, dysplastic ears, auricular tags, conductive and sensorineural deafness, fusion of vertebrae, hemivertebrae, ventricular septal defect.