Marina Boff Lorenzen

Trisomy 18: Experience of a reference hospital from the south of Brazil

Trisomy 18 is a chromosomal syndrome characterized by a broad clinical picture, as well as a very reserved prognosis. The aim of our study was to verify the clinical characteristics and survival of patients diagnosed in a referral hospital in southern Brazil. Our sample consisted of 31 patients, 22 were female (71%), ages ranging from 1 to 1,395 days (median 14 days). The majority had a single cell lineage with full trisomy of chromosome 18 (94%). Concerning pregnancy complications, pre‐eclampsia was the main abnormality described (17%). Fetal ultrasound was performed in 23 cases, and the most frequent abnormalities were polyhydramnios (41%) and intrauterine growth retardation (27%). There were no reports of prenatal identification of the syndrome. Most patients were born by cesarean due to pregnancy and fetal complications and about half of the cases were premature. Congenital heart defects represented the main major malformation observed (94%). Thirty patients (97%) progressed to death (survival ranged from 2 to 780 days, and 87% died within the first 6 months of life). Trisomy 18 is a serious chromosomal disorder with limited survival. Abnormalities of pregnancy appear to be frequent, which can lead to complications for both fetus and mother. The prenatal identification of these patients in our country is still inadequate, resulting in important implications for genetic counseling and management of these patients and their families. And this makes the possibility of interruption of pregnancy, regardless of ethical factors involved, an unlikely option.

New report of a familial case of Moebius syndrome presenting skeletal findings

New Report of a Familial Case of Moebius Syndrome Presenting Skeletal Findings Carla Graziadio, Marina B. Lorenzen, Rafael F.M. Rosa, Louise L.C. Pinto, Paulo R.G. Zen, Giovanni M. Travi, Fabiana Valiatti, and Giorgio A. Paskulin* Clinical Genetics, Universidade Federal de Ciências da Sa ude de Porto Alegre (UFCSPA), Rio Grande do Sul, Brazil Clinical Genetics, Complexo Hospitalar Santa Casa de Porto Alegre (CHSCPA), Rio Grande do Sul, Brazil Department of Clinical Medicine, UFCSPA, Rio Grande do Sul, Brazil Graduate Program in Pathology, UFCSPA, Rio Grande do Sul, Brazil Department of Ophthalmology, CHSCPA, Rio Grande do Sul, Brazil

Trisomy 18: Frequency, types, and prognosis of congenital heart defects in a Brazilian cohort†

Trisomy 18: Frequency, Types, and Prognosis of Congenital Heart Defects in a Brazilian Cohort Rafael F.M. Rosa, Rosana C.M. Rosa, Marina B. Lorenzen, Ceres A.V. de Oliveira, Carla Graziadio, Paulo R.G. Zen, and Giorgio A. Paskulin* Graduate Program in Pathology, Universidade Federal de Ciencias da Sa ude de Porto Alegre (UFCSPA), RS, Brazil Clinical Genetics, UFCSPA and Complexo Hospitalar Santa Casa de Porto Alegre (CHSCPA), RS, Brazil Clinical Genetics, Hospital Materno Infantil Presidente Vargas (HMIPV), RS, Brazil Department of Clinical Medicine, UFCSPA, RS, Brazil Institute of Education and Research, Hospital Moinhos de Vento, RS, Brazil

Limb abnormalities on trisomy 18: evidence for early diagnosis

OBJECTIVE To assess the frequency and types of limb abnormalities observed among patients with trisomy 18, or Edwards syndrome (ES). METHOD The sample consisted of consecutive patients evaluated by a clinical genetics service in the period from 1975 to 2008. The results of the cytogenetic analysis, as well as the clinical data were retrieved from the medical records, with special attention to limb abnormalities findings. All the karyotype analysis was performed at the same laboratory. RESULTS During the study period, 50 patients were identified, 33 (66%) of them females, with ages at the first evaluation ranging from 1 day to 16 years (median 14 days). The single lineage with free trisomy 18 was the most frequent chromosomal disorder (90%). Mosaicism was observed in 10% of the cases. Clenched fist with overlapping fingers was the predominant anomaly of the upper limbs (70%). Other common disorders included the single palmar crease (42%) and hypoplastic nails (36%). Radial abnormalities were found in 11 patients (22%). As for the lower limbs, hypoplastic nails were the most common abnormality (58%), followed by the rocker bottom foot with prominent calcaneus (50%). One patient had unilateral ectrodactyly as well. CONCLUSIONS Despite the classical description, limb anomalies can be much variable in ES. Some patients may show unusual abnormalities, such as radial defects and ectrodactyly. These findings are extremely important for the clinical suspicion and early identification of patients with ES.

Importância da análise cromossômica dos fibroblastos em casos suspeitos de mosaicismo: experiência de um serviço de Genética Clínica

ABSTRACT Objective: To verify clinical characteristics and cytoge-netic findings of patients suspects of having mosaicism and submitted to chromosomal analysis of lymphocytes and fibroblasts through GTG-Banding karyotype. Methods: This is a retrospective analysis of the patients evaluated in the Genetic Clinic of Complexo Hospitalar Santa Casa de Porto Alegre of the Universidade Federal de Ciencias da Saude de Porto Alegre, from 1975 to 2009 (clini-cal data and results of cytogenetic exams were evaluated). Results: Fifteen patients were enrolled, being six males (40%) with ten days to 14 years-old. Alterations in the chro-mosomal analysis of blood were observed in four patients (26.7%) and included one case of balanced translocation [t(2;9)pat] and three cases of mosaicism [mos 45,X/46,X,+mar; mos 46,XY,r(12)/45,XY,-12/47,XY,r(12),+r(12) and mos 46,XY/47,XY,+9]. The patients were then submitted to skin karyotype to confirm or to identify a chromosomal mosaicism. The main reasons for such suspicion in patients with blood karyotype without mosaicism were the presence of hemi-hypertrophy (n=5) and skin spots following the Blaschko lines (n=4). Mosaicism was confirmed in two cases and identified in another two (two cases of mos 46,XX/47,XX,+22). The mos 46,XY/47,XY,+9 was not verified in the fibroblast study.

Importance of the fibroblast chromosomal analysis in suspected cases of mosaicism: experience of a clinical Genetics service

ABSTRACT Objective: To verify clinical characteristics and cytoge-netic findings of patients suspects of having mosaicism and submitted to chromosomal analysis of lymphocytes and fibroblasts through GTG-Banding karyotype. Methods: This is a retrospective analysis of the patients evaluated in the Genetic Clinic of Complexo Hospitalar Santa Casa de Porto Alegre of the Universidade Federal de Ciencias da Saude de Porto Alegre, from 1975 to 2009 (clini-cal data and results of cytogenetic exams were evaluated). Results: Fifteen patients were enrolled, being six males (40%) with ten days to 14 years-old. Alterations in the chro-mosomal analysis of blood were observed in four patients (26.7%) and included one case of balanced translocation [t(2;9)pat] and three cases of mosaicism [mos 45,X/46,X,+mar; mos 46,XY,r(12)/45,XY,-12/47,XY,r(12),+r(12) and mos 46,XY/47,XY,+9]. The patients were then submitted to skin karyotype to confirm or to identify a chromosomal mosaicism. The main reasons for such suspicion in patients with blood karyotype without mosaicism were the presence of hemi-hypertrophy (n=5) and skin spots following the Blaschko lines (n=4). Mosaicism was confirmed in two cases and identified in another two (two cases of mos 46,XX/47,XX,+22). The mos 46,XY/47,XY,+9 was not verified in the fibroblast study.

Trisomy 18 (Edwards syndrome) and major gastrointestinal malformations.

Trisomy 18 or Edwards syndrome is a chromosomal disease characterized by involvement of many organs and systems, and limited survival.1 The aim of our study was to determine the frequency and types of major gastrointestinal abnormalities observed among patients with Edwards syndrome. The sample consisted of patients consecutively evaluated over the period between 1975 and 2008 in a clinical genetics service at a referral hospital in southern Brazil. Clinical data and karyotype results were gathered from this hospital’s medical records. We use Fisher’s exact test (two-tailed) to compare frequencies (P values < 0.05 were considered significant). Thus, our sample was composed of 50 patients, of whom 33 (66%) were female. Their ages at the first evaluation ranged from 1 day to 16 years (median 14 days). Eight of the patients (16%) were born in that hospital. Presence of a single lineage with free trisomy of chromosome 18 was the main abnormality, observed in 90% of the cases. The remainder consisted of patients with mosaicism. Major gastrointestinal abnormalities were observed in eight patients (16%): two cases of esophageal atresia (4%), three of tracheoesophageal fistula (6%) (one associated with esophageal atresia), one of diaphragmatic hernia (2%) and three of omphalocele (6%). Among these eight patients, five (62%) were female. Their ages at the time of the initial evaluation ranged from one to 70 days (median 7.5 days). Only two patients (25%) presented a clinical suspicion of Edwards syndrome. Additional abnormalities, including minor and major anomalies, were observed in all cases. These included dysmorphic features like a clenched fist with overlapping fingers and major malformations like congenital heart defects. None had a chromosomal constitution with mosaicism. Three patients underwent surgical correction of their defects (one with esophageal atresia, one with tracheoesophageal fistula and one with omphalocele). In all cases, the diagnosis of Edwards syndrome was made only after surgery. Gastrointestinal malformations are frequent among patients with Edwards syndrome. In the literature, the frequency of esophageal atresia among these patients ranges from 16 to 18%.2-4 Despite the frequency of 4% observed in our study, no statistically significant difference was seen using Fisher’s exact test when we compared it with these studies. However, it is noteworthy that the samples in other studies (n = 24 to 39 patients) were smaller than in ours (n = 50). Patients with esophageal atresia usually present the associated finding of tracheoesophageal fistula,4,5 as observed in one of our two patients. Omphalocele has been described in less than 10% of the patients,2-5 which is compatible with the rate in our study (6%). Despite the possible association described in the literature,5 none of our patients with omphalocele presented a neural tube defect. Diaphragmatic hernia is considered to be a less common abnormality, and has been described in less than 8% of the patients.2-4 This frequency was similar to our study (2%). Thus, Edwards syndrome should always be considered among dysmorphic children presenting these major gastrointestinal malformations. Diagnosing it is important for proper management and for determining the prognosis for these patients. IPhD. Clinical Geneticist, Universidade Federal de Ciencias da Saude de Porto Alegre (UFCSPA) and Complexo Hospitalar Santa Casa de Porto Alegre (CHSCPA), Porto Alegre, Rio Grande do Sul, Brazil. IIMD. Postgraduate, Postgraduate Program on Pathology, Universidade Federal de Ciencias da Saude de Porto Alegre (UFCSPA), Porto Alegre, Rio Grande do Sul, Brazil. IIIUndergraduate Medical Student, Universidade Federal de Ciencias da Saude de Porto Alegre (UFCSPA), Porto Alegre, Rio Grande do Sul, Brazil. IVPhD. Adjunct Professor of Clinical Genetics and Professor of the Postgraduate Program on Pathology, Universidade Federal de Ciencias da Saude de Porto Alegre (UFCSPA), and Clinical Geneticist, Universidade Federal de Ciencias da Saude de Porto Alegre (UFCSPA) and Complexo Hospitalar Santa Casa de Porto Alegre (CHSCPA), Porto Alegre, Rio Grande do Sul, Brazil. VMD. Professor, Instituto de Educacao e Pesquisa (IEP), Hospital Moinhos de Vento (HMV), Porto Alegre, Rio Grande do Sul, Brazil. VIMD. Postgraduate Student, Postgraduate Program on Pathology, and Assistant Professor of Clinical Genetics, Universidade Federal de Ciencias da Saude de Porto Alegre (UFCSPA), and Clinical Geneticist, Universidade Federal de Ciencias da Saude de Porto Alegre (UFCSPA) and Complexo Hospitalar Santa Casa de Porto Alegre (CHSCPA), Porto Alegre, Rio Grande do Sul, Brazil. VIIPhD. Associate Professor of Clinical Genetics and Coordinator of the Postgraduate Program on Pathology, Universidade Federal de Ciencias da Saude de Porto Alegre (UFCSPA), and Clinical Geneticist, Universidade Federal de Ciencias da Saude de Porto Alegre (UFCSPA) and Complexo Hospitalar Santa Casa de Porto Alegre (CHSCPA), Porto Alegre, Rio Grande do Sul, Brazil.

Craniofacial abnormalities among patients with Edwards Syndrome

OBJECTIVE To determine the frequency and types of craniofacial abnormalities observed in patients with trisomy 18 or Edwards syndrome (ES). METHODS This descriptive and retrospective study of a case series included all patients diagnosed with ES in a Clinical Genetics Service of a reference hospital in Southern Brazil from 1975 to 2008. The results of the karyotypic analysis, along with clinical data, were collected from medical records. RESULTS: The sample consisted of 50 patients, of which 66% were female. The median age at first evaluation was 14 days. Regarding the karyotypes, full trisomy of chromosome 18 was the main alteration (90%). Mosaicism was observed in 10%. The main craniofacial abnormalities were: microretrognathia (76%), abnormalities of the ear helix/dysplastic ears (70%), prominent occiput (52%), posteriorly rotated (46%) and low set ears (44%), and short palpebral fissures/blepharophimosis (46%). Other uncommon - but relevant - abnormalities included: microtia (18%), orofacial clefts (12%), preauricular tags (10%), facial palsy (4%), encephalocele (4%), absence of external auditory canal (2%) and asymmetric face (2%). One patient had an initial suspicion of oculo-auriculo-vertebral spectrum (OAVS) or Goldenhar syndrome. CONCLUSIONS: Despite the literature description of a characteristic clinical presentation for ES, craniofacial alterations may be variable among these patients. The OAVS findings in this sample are noteworthy. The association of ES with OAVS has been reported once in the literature.

Múltiplas hiperintensidades no sistema nervoso central em uma criança com neurofibromatose do tipo 1

Objective: To report a child with neurofibromatosis type 1 presenting the occasional central nervous system feature of multiple hyperintensities and a prechiasmatic hamartomatous lesion. Case description: The patient is a four-year old black boy whose father presented cafe-au-lait spots and history of ear tumor surgery. The neuropsychomotor development of the child was within the normal range, without seizures

Trisomy 18 and eye anomalies

Trisomy 18 and Eye Anomalies Jamile D. Correia, Ernani B. da Rosa, Dani elle B. Silveira, Elisa P. E. Correia, Marina B. Lorenzen, Giovanni M. Travi, Rosana C. M. Rosa, Paulo R. G. Zen, Tatiana D. Zen, and Rafael F. M. Rosa* Graduate Program in Pathology, Universidade Federal de Ciências da Sa ude de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil Graduation in Medicine, UFCSPA, Porto Alegre, RS, Brazil Pediatric Ophthalmology, Hospital da CrianS ca Santo Antônio (HCSA)/Complexo Hospitalar Santa Casa de Porto Alegre (CHSCPA), Porto Alegre, RS, Brazil Graduate Program in Biosciences, UFCSPA, Porto Alegre, RS, Brazil Clinical Genetics, UFCSPA and CHSCPA, Porto Alegre, RS, Brazil Pharmacy, Faculdade de Ciências da Sa ude, Centro Universit ario Ritter dos Reis—UniRitter, Porto Alegre, RS, Brazil