Assessment of Intellectual and Visuo Spatial Abilities in Children and Adults with Williams Syndrome / Evaluación de habilidades intelectuales y visuoespaciales de niños y adultos con Síndrome de Williams

The Williams-Beuren syndrome (SWB), also known as Williams syndrome, is a contiguous gene deletion of the region 7q.11.23. The main clinical characteristics are typical faces, supravalvular aortic stenosis, failure to thrive, short stature, transient neonatal hypercalcemia, delayed language, friendly personality, hyperacusis and intellectual disability. The diagnosis of SWB is confirmed by the detection of micro deletion by different techniques of molecular cytogenetics, FISH, MLPA or polymorphic markers. This study assessed the verbal intelligence quotient (IQ) and performance and visuo-spatial skills in children and adults with WBS. The composed group was of 31 WBS patients (19 M and 12 F), whose ages ranged from 9 to 26 years (M 14.45 y). All patients had the diagnosis confirmed molecularly. The tests used were the WISC-III, WAIS-III and Rey-Osterrieth Complex Figure Test. The results indicated a total IQ ranged from 51 to 86 (M 63): 22 with mild intellectual disability, 4 with moderate intellectual disability, 4 borderlines and 1 below the normal media. All patients had marked visual-spatial deficits. The results suggest nonverbal reasoning, visuo-spatial perception, spatial representation, working memory, motor planning and executive functions are very affected in this group.

El síndrome de Williams-Beuren (SWB), también conocido como síndrome de Williams, es un síndrome de deleción de genes contiguos de la región 7q.11.23. Se caracteriza por dimorfismo facial típico asociado a anomalías cardiovasculares, personalidad amigable, hiperacusia y deficiencia intelectual. El diagnóstico del SWB es confirmado por la detección de microdeleción a partir de las diferentes técnicas de citogenética molecular: FISH, marcadores polimórficos o MLPA. Este estudio evaluó el cociente intelectual verbal y manipulativo, así como las habilidades visuoespaciales en niños y adultos con SWB. El grupo estuvo formado por 31 pacientes con SWB (19 de sexo masculino y 12 de sexo femenino), cuyas edades variaron entre 9 y 26 años (media 14.45 años). Todos los pacientes tenían el diagnóstico confirmado molecularmente. Los test utilizados fueron las escalas WISC-III, WAIS-III y el Test Figuras Complejas Rey-Osterrieth. Los resultados indicaron un cociente intelectual que osciló de 51 a 86 (media 63), distribuido así: 22 con deficiencia intelectual leve, 4 con deficiencia intelectual moderada, 4 limítrofes, 1 en la media inferior. Todos los pacientes presentaron déficit visuoespacial. Los resultados sugieren que el razonamiento no verbal, la percepción visuoespacial, la representación espacial, la memoria de trabajo, la planificación motora y las funciones ejecutivas están muy comprometidos en el grupo estudiado.

Angiokeratoma: a cutaneous marker of Fabry's disease.

The initial symptoms of Fabry's disease (FD) may seem harmless and may delay its diagnosis. A survey and screening for FD were performed on men with biopsy-proven angiokeratoma and some of their relatives (n = 29). Three patients were identified. Dermatologists should be aware of this prominent early feature and investigate unexplained cutaneous vascular lesions to detect FD.

CHILD syndrome caused by a deletion of exons 6-8 of the NSDHL gene.

The X-linked dominant CHILD syndrome (congenital hemidysplasia with ichthyosiform nevus and limb defects) is a rare developmental defect characterized by a strictly lateralized inflammatory nevus. In the majority of cases, the right side of the body is affected. Ipsilateral hypoplastic lesions may involve the brain, skeletal structures, lungs, heart or kidneys. We describe a case of CHILD syndrome involving the left side of the body. Absence of metacarpal, metatarsal and phalangeal bones of the left hand and foot resulted in oligodactyly, with only 3 fingers and 1 toe. An ipsilateral inflammatory epidermal nevus with hyperkeratosis, parakeratosis, acanthosis and perivascular lymphohistiocytic infiltrate was strictly confined to the left half of the patient's body. The phenotype was shown to be associated with a deletion of exons 6-8 of the X-linked NSDHL gene, confirming that CHILD syndrome is due to loss of function of an enzyme involved in cholesterol biosynthesis.

Friedreich's ataxia: clinical and molecular study of 25 Brazilian cases.

INTRODUCTION: Friedreich's ataxia is a neurodegenerative disorder whose clinical diagnostic criteria for typical cases basically include: a) early age of onset (< 20 or 25 years), b) autosomal recessive inheritance, c) progressive ataxia of limbs and gait, and d) absence of lower limb tendon reflexes. METHODS: We studied the frequency and the size of expanded GAA and their influence on neurologic findings, age at onset, and disease progression in 25 Brazilian patients with clinical diagnosis of Friedreich's ataxia - 19 typical and 6 atypical - using a long-range PCR test. RESULTS: Abnormalities in cerebellar signs, in electrocardiography, and pes cavus occurred more frequently in typical cases; however, plantar response and speech were more frequently normal in this group when the both typical and atypical cases were compared. Homozygous GAA expansion repeats were detected in 17 cases (68%) - all typical cases. In 8 patients (32%) (6 atypical and 2 typical), no expansion was observed, ruling out the diagnosis of Friedreich's ataxia. In cases with GAA expansions, foot deformity, cardiac abnormalities, and some neurologic findings occurred more frequently; however, abnormalities in cranial nerves and in tomographic findings were detected less frequently than in patients without GAA expansions. DISCUSSION: Molecular analysis was imperative for the diagnosis of Friedreich's ataxia, not only for typical cases but also for atypical ones. There was no genotype-phenotype correlation. Diagnosis based only on clinical findings is limited; however, it aids in better screening for suspected cases that should be tested. Evaluation for vitamin E deficiency is recommended, especially in cases without GAA expansion.

Cardiac findings in 31 patients with Noonan's syndrome.

OBJECTIVE: To evaluate cardiac findings in 31 Noonan syndrome patients. METHODS: Thirty-one (18 males and 13 females)patients from 26 families affected with Noonan's syndrome were evaluated from the cardiac point of view with electrocardiography and Doppler echocardiography. RESULTS: Twenty patients had some type of cardiac abnormality. The most frequent was pulmonary valve stenosis followed by hypertrophic myocardiopathy, commonly associated with valve defects. Upper deviation of the QRS axis was observed in 80% of these patients. CONCLUSION: In view of the high frequency and diversity of cardiac abnormalities present in Noonan syndrome, cardiac evaluation with electrocardiography and echocardiography should be performed in all patients diagnostically suspected of having this disease.

AEC syndrome and CHAND syndrome: further evidence of clinical overlapping in the ectodermal dysplasias.

Among the ectodermal dysplasias, there are several examples of overlapping phenotypes in disorders that are considered distinct. We report a 5-year-old boy born to nonconsanguineous parents and presenting with ectodermal dysplasia, ankyloblepharon filiforme adnatum, and bilateral choanal atresia consistent with the diagnosis of AEC syndrome. We compare the findings in our patient with the previous reported cases and discuss the overlapping phenotype of this disorder with CHAND syndrome.

[The importance of genetics in the public health care system: report on the closing down of a genetics division in São Paulo, Brazil]. / Importância da genética no serviço público: relato da extinção de um setor de genética no Município de São Paulo, Brasil.

The availability of genetics services in hospitals should be an issue of public concern. Having genetics services helps shorten the time spent in making diagnoses and reduces the average number of inpatient days; it also helps accelerate the choice of adequate treatments, prevents or minimizes sequelae, and, ultimately, reduces costs. The objective of the present study was to describe the closing down in 1996 of the genetics division at the Menino Jesus Children's Hospital, a pediatric institution located in the city of São Paulo, SP, Brazil. A retrospective analysis was carried out of the work performed by this division between 1992 and 1996, with an emphasis on the detection of chromosomal abnormalities. Of all cases assessed during the study period, 571 were entered into a database. Some kind of chromosomal abnormality was observed in 20% of the 350 karyotypes performed. The existence of genetics services in hospitals helps minimize the appearance of clinical symptoms in carriers of genetic abnormalities, improves the quality of life of these patients, and enables them to receive information regarding risk of recurrence, while preventing the waste of resources that results from tests that are costly and unnecessary. Such benefits amply justify the investment in setting up genetics services of the type described here.

Clinical and laboratorial study of 19 cases of mucopolysaccharidoses.

UNLABELLED: The mucopolysaccharidoses (MPS) are a heterogeneous group of inborn errors of lysosomal glycosaminoglycan (GAG) metabolism. The importance of this group of disorders among the inborn errors of metabolism led us to report 19 cases. METHOD: We performed clinical, radiological, and biochemical evaluations of the suspected patients, which allowed us to establish a definite diagnosis in 19 cases. RESULTS: Not all patients showed increased GAG levels in urine; enzyme assays should be performed in all cases with strong clinical suspicion. The diagnosis was made on average at the age of 48 months, and the 19 MPS cases, after a full clinical, radiological, and biochemical study, were classified as follows: Hurler - MPS I (1 case); Hunter - MPS II (2 cases); Sanfilippo - MPS III (2 cases); Morquio - MPS IV (4 cases); Maroteaux-Lamy - MPS VI (9 cases); and Sly - MPS VII (1 case). DISCUSSION: The high relative frequency of Maroteaux-Lamy disease contrasts with most reports in the literature and could express a population variability.

Prenatal exposure to misoprostol and vascular disruption defects: a case-control study.

Prenatal exposure to misoprostol has been associated with Moebius and limb defects. Vascular disruption has been proposed as the mechanism for these teratogenic effects. The present study is a multicenter, case-control study that was designed to compare the frequency of prenatal misoprostol use between mothers of Brazilian children diagnosed with vascular disruption defects and matched control mothers of children diagnosed with other types of defects. A total of 93 cases and 279 controls were recruited in eight participating centers. Prenatal exposure was identified in 32 infants diagnosed with vascular disruption defects (34.4%) compared with only 12 (4.3%) in the control group (P<0.0000001). Our data suggest that prenatal exposure to misoprostol is associated to the occurrence of vascular disruption defects in the newborns.

Clinical and radiological aspects in Melnick-Needles syndrome.

Melnick-Needles syndrome is an X-linked dominant bone dysplasia, lethal in males, characterized by a typical facies and characteristic radiological findings: including sclerosis of skull base and mastoids. S-shaped appearance of tibia; cortical irregularities with a ribbon appearance of the ribs. About 48 well-documented cases have been reported, most of them were sporadic. Parental transmission has been published in only 11 kindreds. We are presenting the first Brazilian family with mother-daughter transmission. The proposita presented the typical clinical and radiological features with characteristic facies, severe thoracic cage restriction and pulmonary hypertension. Her mother was more mildly affected.

Noonan syndrome: a clinical and genetic study of 31 patients.

Noonan syndrome is a multiple congenital anomaly syndrome, inherited in an autosomal dominant pattern. We studied 31 patients (18 males and 13 females) affected by this disorder regarding their clinical and genetic characteristics. The most frequent clinical findings were short stature (71%); craniofacial dysmorphisms, especially hypertelorism, ptosis, downslanting of the palpebral fissures; short or webbed neck (87%); cardiac anomalies (65%), and fetal pads in fingers and toes (70%). After studying the probands' first-degree relatives, we made the diagnosis of Noonan syndrome in more than one family member in three families. Therefore, the majority of our cases were sporadic.

Modos ventilatorios y retirada de la ventilación mecánica en pediatría: corte de prevalencia, estudio multicéntrico / Modes of ventilation and weaning of the mechanical ventilation in pediatrics: prevalence cut-multicentric study

Objetivo: Conocer la proporción de los pacientes que requieren ventilación mecánica (AVM) entre los ingresados en la unidad de cuidados intensivos pediátricos (UCIP) y los modos de ventilación utilizados. Material y métodos: Se realizó un estudio observacional y prospectivo de la ventilación mecánica en 12 UCIP distribuidas por Argentina durante 1997, en dos fechas climatológicas diferenciadas, 13 de mayo (M97) y 13 de agosto (A97). Se utilizó un cuestionario cumplmentado para cada paciente. Resultados: 92 pacientes ingresaron a la UCIP en M97 y 107 en A97. El 54,3 por ciento (IC 97 por ciento 47,6-61) y 51,4 por ciento (IC 95 por ciento 44,7-58,1) estaban en AVM respectivamente. La causa más frecuente de ingreso al respirador fue la insuficiencia respiratoria aguda 62 por ciento (IC 95 por ciento 48,5-75,4) en M97 y 61,8 por ciento (IC 95 por ciento 48,9-74,6) en A97. El modo de ventilación más utilizado en ambos cortes fue la IMV/SIMV 48 por ciento (IC 95 por ciento 35-61) y 52,7 (IC 95 por ciento 39,5-65,7). El porcentaje de pacientes en proceso de retirada de la ventilación fue del 40 por ciento (IC 95 por ciento 26,5-53) en M97 y 38 por ciento (IC 95 por ciento 25,2-50,8) en A97. Conclusiones: Nuestro estudio, que es el primero realizado en pediatría con carácter multicéntrico y con éstos objetivos, muestra un porcentaje de pacientes ventilados en torno al 50 por ciento. Igual porcentaje de pacientes estaban en ventilación con IMV/SIMV y los modos más recientes de ventilación fueron escasamente utilizados. Parece aconsejable adecuar las adquisiciones de los respiradores a las patologías que haya que tratar. La utilización racional de los recursos será sin duda uno de los objetivos en los próximos años

Modos ventilatorios y retirada de la ventilación mecánica en pediatría: corte de prevalencia, estudio multicéntrico / Modes of ventilation and weaning of the mechanical ventilation in pediatrics: prevalence cut-multicentric study

Objetivo: Conocer la proporción de los pacientes que requieren ventilación mecánica (AVM) entre los ingresados en la unidad de cuidados intensivos pediátricos (UCIP) y los modos de ventilación utilizados. Material y métodos: Se realizó un estudio observacional y prospectivo de la ventilación mecánica en 12 UCIP distribuidas por Argentina durante 1997, en dos fechas climatológicas diferenciadas, 13 de mayo (M97) y 13 de agosto (A97). Se utilizó un cuestionario cumplmentado para cada paciente. Resultados: 92 pacientes ingresaron a la UCIP en M97 y 107 en A97. El 54,3 por ciento (IC 97 por ciento 47,6-61) y 51,4 por ciento (IC 95 por ciento 44,7-58,1) estaban en AVM respectivamente. La causa más frecuente de ingreso al respirador fue la insuficiencia respiratoria aguda 62 por ciento (IC 95 por ciento 48,5-75,4) en M97 y 61,8 por ciento (IC 95 por ciento 48,9-74,6) en A97. El modo de ventilación más utilizado en ambos cortes fue la IMV/SIMV 48 por ciento (IC 95 por ciento 35-61) y 52,7 (IC 95 por ciento 39,5-65,7). El porcentaje de pacientes en proceso de retirada de la ventilación fue del 40 por ciento (IC 95 por ciento 26,5-53) en M97 y 38 por ciento (IC 95 por ciento 25,2-50,8) en A97. Conclusiones: Nuestro estudio, que es el primero realizado en pediatría con carácter multicéntrico y con éstos objetivos, muestra un porcentaje de pacientes ventilados en torno al 50 por ciento. Igual porcentaje de pacientes estaban en ventilación con IMV/SIMV y los modos más recientes de ventilación fueron escasamente utilizados. Parece aconsejable adecuar las adquisiciones de los respiradores a las patologías que haya que tratar. La utilización racional de los recursos será sin duda uno de los objetivos en los próximos años (AU)