Vinicius Freitas de Mattos

Clinical features and prognosis of a sample of patients with trisomy 13 (Patau syndrome) from Brazil.

Trisomy 13 or Patau syndrome (PS) is a chromosomal disorder characterized by a well known presentation of multiple congenital anomalies. Our objective was to determine the clinical features and prognosis observed in a sample of patients with PS. The series was composed of patients with diagnosis of PS consecutively evaluated by a Clinical Genetics Service from a reference hospital of southern Brazil, in the period between 1975 and 2012. Statistical analysis was performed using PEPI program (version 4.0), with two‐tailed Fishers exact test for comparison of frequencies (P < 0.05). The sample consisted of 30 patients, 60% male, median age at first evaluation of 9 days. Full trisomy of chromosome 13 was the main cytogenetic alteration (73%). The major clinical findings included: cryptorchidism (78%), abnormal auricles (77%), congenital heart defects (76%), polydactyly (63%), microphthalmia (60%) and micrognathia (50%). Four patients (13%) simultaneously had micro/anophthalmia, oral clefts and polydactyly. Some findings were only observed in our sample and included, among others, preauricular tags (10%), duplication of the hallux (3%) and spots following the lines of Blaschko (3%). Mosaicism (20% of cases) had a statistically significant association only with absence of cryptorchidism. The median of survival was 26 days. Patients with and without mosaicism had similar median of survival. Our findings, in agreement with the literature, show that the anomalies in patients with PS can be quite variable, sometimes even atypical. There is no pathognomonic finding, which may make the early identification of these patients challenging.

Gómez-López-Hernández Syndrome in a Child Born to Consanguineous Parents: New Evidence for an Autosomal-Recessive Pattern of Inheritance?

BACKGROUND Gómez-López-Hernández syndrome is a rare genetic disease characterized by scalp alopecia with trigeminal anesthesia, brachycephaly or turribrachycephaly, midface retrusion, and rhombencephalosynapsis. We report the second case with this condition who presented with consanguineous parents. PATIENT This boy was evaluated shortly after birth because of suspected craniosynostosis. He was the only son of healthy, consanguineous parents (his maternal grandmother and his paternal great-grandfather were siblings). His examination was notable for turribrachycephaly, prominent forehead, bilateral parietotemporal alopecia, midfacial retrusion, anteverted nostrils, micrognathia, low-set and posteriorly rotated ears, and short neck with redundant skin. Radiographs and tridimensional computed tomography scan of skull revealed lambdoid craniosynostosis. Brain magnetic resonance imaging revealed complete rhombencephalosynapsis, aqueductal stenosis, fused colliculi, abnormal superior cerebellar penducle, mild ventriculomegaly, and dysgenesis of the corpus callosum. CONCLUSIONS Since its first description, 34 patients with this condition have been reported. The etiology of Gómez-López-Hernández syndrome is unknown. However, it is noteworthy that the patient in this report presented with a family history of consanguinity because this finding reinforces the possibility of an autosomal-recessive inheritance for this condition.

Trisomy 13 (Patau syndrome) and congenital heart defects

Trisomy 13 (Patau Syndrome) and Congenital Heart Defects Janaina B. Polli, Daniela de P. Groff, Patrı́cia Petry, Vinı́cius F. Mattos, Rosana C. M. Rosa, Paulo R. G. Zen, Carla Graziadio, Giorgio A. Paskulin, and Rafael F. M. Rosa* Pediatrics Service, Hospital Materno Infantil Presidente Vargas (HMIPV), Porto Alegre, RS, Brazil Clinical Genetics, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA) and Complexo Hospitalar Santa Casa de Porto Alegre (CHSCPA), Porto Alegre, RS, Brazil Graduate Program in Pathology, UFCSPA, Porto Alegre, RS, Brazil Clinical Genetics, HMIPV, Porto Alegre, RS, Brazil

Clinical and cytogenetic features of a Brazilian sample of patients with phenotype of oculo-auriculo-vertebral spectrum: a cross-sectional study

CONTEXT AND OBJECTIVE Oculo-auriculo-vertebral spectrum (OAVS) is considered to be a defect of embryogenesis involving structures originating from the first branchial arches. Our objective was to describe the clinical and cytogenetic findings from a sample of patients with the phenotype of OAVS. DESIGN AND SETTING Cross-sectional study in a referral hospital in southern Brazil. METHODS The sample consisted of 23 patients who presented clinical findings in at least two of these four areas: orocraniofacial, ocular, auricular and vertebral. The patients underwent a clinical protocol and cytogenetic evaluation through high-resolution karyotyping, fluorescence in situ hybridization for 5p and 22q11 microdeletions and investigation of chromosomal instability for Fanconi anemia. RESULTS Cytogenetic abnormalities were observed in three cases (13%) and consisted of: 47,XX,+mar; mos 47,XX,+mar/46,XX; and 46,XX,t(6;10)(q13; q24). We observed cases of OAVS with histories of gestational exposition to fluoxetine, retinoic acid and crack. One of our patients was a discordant monozygotic twin who had shown asymmetrical growth restriction during pregnancy. Our patients with OAVS were characterized by a broad clinical spectrum and some presented atypical findings such as lower-limb reduction defect and a tumor in the right arm, suggestive of hemangioma/lymphangioma. CONCLUSIONS We found a wide range of clinical characteristics among the patients with OAVS. Different chromosomal abnormalities and gestational expositions were also observed. Thus, our findings highlight the heterogeneity of the etiology of OAVS and the importance of these factors in the clinical and cytogenetic evaluation of these patients.

Nager syndrome and Pierre Robin sequence

Nager syndrome is considered a rare genetic syndrome characterized by craniofacial and radial anomalies. Pierre Robin sequence is a triad that includes micrognathia, cleft palate and glossoptosis. The present patient had typical findings of Nager syndrome and Pierre Robin sequence. He progressed to severe respiratory distress, requiring mechanical ventilation and tracheostomy. At 1 year and 11 months, he had episodes of cardiorespiratory arrest and died. In the literature review, we identified the clinical description of 44 patients with Nager syndrome. Among them, 93.1% had micrognathia, 38.6% cleft palate and 11.3% glossoptosis. Only one (2.3%) had all three features, as observed in the present patient. Therefore, despite the fact that the features of Pierre Robin sequence are common, there are few patients who have the complete triad. It is noteworthy, however, that they may be associated with respiratory distress, which may put the patients life at risk.

Importance of a multidisciplinary approach and monitoring in fetal warfarin syndrome

Warfarin is a synthetic oral anticoagulant that crosses the placenta and can lead to a number of congenital abnormalities known as fetal warfarin syndrome. Our aim is to report on the follow‐up from birth to age 8 years of a patient with fetal warfarin syndrome. He presented significant respiratory dysfunction, as well as dental and speech and language complications. The patient was the second child of a mother who took warfarin during pregnancy due to a metallic heart valve. The patient had respiratory dysfunction at birth. On physical examination, he had a hypoplastic nose, pectus excavatum, and clubbing of the fingers. Nasal fibrobronchoscopy showed upper airway obstruction due to narrowing of the nasal cavities. He underwent surgical correction with Max Pereira graft, zetaplasty, and osteotomies for the piriform aperture. At dental evaluation, he had caries and delayed eruption of the upper incisors. Speech and language assessment revealed high palate, mouth breathing, little nasal patency, and shortened upper lip. Auditory long latency and cognitive‐related potential to auditory stimuli demonstrated functional changes in the cortical auditory pathways. We believe that the frequency of certain findings observed in our patient may be higher in fetal warfarin syndrome than is appreciated, since a significant number result in abortions, stillbirths, or children evaluated in the first year of life without a follow‐up. Thus, a multidisciplinary approach and long‐term monitoring of these patients may be necessary.

Microcephaly-chorioretinopathy syndrome, autosomal recessive form. A case report

CONTEXT The autosomal recessive form of microcephaly-chorioretinopathy syndrome is a rare genetic condition that is considered to be an important differential diagnosis with congenital toxoplasmosis. CASE REPORT Our patient was a seven-year-old white boy who was initially diagnosed with congenital toxoplasmosis. However, his serological tests for congenital infections, including toxoplasmosis, were negative. He was the first child of young, healthy and consanguineous parents (fourth-degree relatives). The parents had normal head circumferences and intelligence. The patient presented microcephaly and specific abnormalities of the retina, with multiple diffuse oval areas of pigmentation and patches of chorioretinal atrophy associated with diffuse pigmentation of the fundus. Ophthalmological evaluations on the parents were normal. A computed tomography scan of the childs head showed slight dilation of lateral ventricles and basal cisterns without evidence of calcifications. We did not find any lymphedema in his hands and feet. He had postnatal growth retardation, severe mental retardation and cerebral palsy. CONCLUSIONS The finding of chorioretinal lesions in a child with microcephaly should raise suspicions of the autosomal recessive form of microcephaly-chorioretinopathy syndrome, especially in cases with an atypical pattern of eye fundus and consanguinity. A specific diagnosis is essential for an appropriate clinical evaluation and for genetic counseling for the patients and their families.

Cytogenetic profile of patients with Down syndrome in southern Brazil.

The aim of our study was to investigate the cytogenetic findings of patients with Down syndrome who were diagnosed by a clinical genetics service in southern Brazil between 1975 and 2008. All karyotyping was performed in the same labo-ratory, using the G-bands by trypsin using Giemsa (GTG) technique. A mean of 22 cells per case were analyzed (range: 5 – 80).Our sample comprised 644 patients (364 males and 280 females). Full trisomy of chromo-some 21 was the predominant alteration observed in 598 of these patients (92.9%). Chromosomal abnormalities of structural type were observed in 26 patients (4%). These were composed of Robertsonian translocations involving chromosome 21 and chromosomes 14 (n = 12), 21 (n = 10), 15 (n = 1) and 22 (n = 1). In addition, two cases showed a reciprocal translocation, one of them involving chromosomes 21 and 5 and another with a complex translocation involv -ing chromosomes 5, 21 and 22. Among the patients with structural chromosomal abnormali-ties, karyotyping analysis on the parents was performed in relation to 11 patients. Structurally balanced alterations were detected in five of them (45.5%). Mosaicism was identified in 20 patients (3.1%) and usually involved two cell lines: one normal and one with trisomy 21 (n = 15). However, two patients (10%) presented mosaicism involving three cell lines. Five cases (25%) showed a cell line with double aneuploidy, and four of them involved chromosomes 9, 14, 21 and X, respectively. The fifth patient presented an additional marker chromosome. Six patients (30%) among the 20 had mosaicism for trisomy 21 that was lower than 10%. The mean number of cells analyzed in these cases was 42 (the maximum was 80 cells; range: 15 – 80).In our review of the literature, using the PubMed, SciELO and Lilacs databases, we did not identify any studies that evaluated the cytogenetic profile of patients with Down syndrome in Latin America. The frequencies of the different changes to chromosome 21 observed in our study were consistent with those described in the literature.

Trisomy 13 and gallbladder agenesis

Trisomy 13 and Gallbladder Agenesis Rafael F. M. Rosa, Elisa P. E. Correia, Vict oria B. Guimar~aes, J ulia S. Trombetta, Luciana A. Beltr~ao, Karen L. P. Lliguin, Vinicius Freitas de Mattos, Rosana C. M. Rosa, and Paulo R. G. Zen* Graduate Program in Pathology, Universidade Federal de Ciências da Sa ude de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil Graduate Program in Biosciences, Universidade Federal de Ciências da Sa ude de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil Clinical Genetics, Universidade Federal de Ciências da Sa ude de Porto Alegre (UFCSPA) and Complexo Hospitalar Santa Casa de Porto Alegre (CHSCPA), Porto Alegre, RS, Brazil Graduation in Medicine, UFCSPA, Porto Alegre, RS, Brazil

Role of hypocalcemia in identification of 22q11 deletion syndrome among patients with congenital heart defects

a Clinical Genetics, Universidade Federal de Ciencias da Saude de Porto Alegre (UFCSPA) and Complexo Hospitalar Santa Casa de Porto Alegre (CHSCPA), RS, Brazil b Graduation in Medicine, Universidade Federal de Ciencias da Saude de Porto Alegre (UFCSPA), RS, Brazil c Graduate Program in Pathology, Universidade Federal de Ciencias da Saude de Porto Alegre (UFCSPA), RS, Brazil d Human Genetics, Universidade Federal de Ciencias da Saude de Porto Alegre (UFCSPA), RS, Brazil e School of Medicine, Division of Medical Oncology, University of Colorado Denver, CO, USA f Clinical Genetics, Hospital Materno Infantil Presidente Vargas (HMIPV), RS, Brazil