A clinical follow-up of 35 Brazilian patients with Prader-Willi Syndrome

OBJECTIVE: Prader-Willi Syndrome is a common etiology of syndromic obesity that is typically caused by either a paternal microdeletion of a region in chromosome 15 (microdeletions) or a maternal uniparental disomy of this chromosome. The purpose of this study was to describe the most significant clinical features of 35 Brazilian patients with molecularly confirmed Prader-Willi syndrome and to determine the effects of growth hormone treatment on clinical outcomes. METHODS: A retrospective study was performed based on the medical records of a cohort of 35 patients diagnosed with Prader-Willi syndrome. The main clinical characteristics were compared between the group of patients presenting with microdeletions and the group presenting with maternal uniparental disomy of chromosome 15. Curves for height/length, weight and body mass index were constructed and compared between Prader-Willi syndrome patients treated with and without growth hormone to determine how growth hormone treatment affected body composition. The curves for these patient groups were also compared with curves for the normal population. RESULTS: No significant differences were identified between patients with microdeletions and patients with maternal uniparental disomy for any of the clinical parameters measured. Growth hormone treatment considerably improved the control of weight gain and body mass index for female patients but had no effect on either parameter in male patients. Growth hormone treatment did not affect height/length in either gender. CONCLUSION: The prevalence rates of several clinical features in this study are in agreement with the rates reported in the literature. Additionally, we found modest benefits of growth hormone treatment but failed to demonstrate differences between patients with microdeletions and those with maternal uniparental disomy. The control of weight gain in patients with Prader-Willi syndrome is complex and does not depend exclusively on growth hormone treatment.

Synteny of human chromosomes 14 and 15 in the platyrrhines (Primates, Platyrrhini)

In order to study the intra- and interspecific variability of the 14/15 association in Platyrrhini, we analyzed 15 species from 13 genera, including species that had not been described yet. The DNA libraries of human chromosomes 14 and 15 were hybridized to metaphases of Alouatta guariba clamitans, A. caraya, A. sara, Ateles paniscus chamek, Lagothrix lagothricha, Brachyteles arachnoides, Saguinus midas midas, Leontopithecus chrysomelas, Callimico goeldii, Callithrix sp., Cebus apella, Aotus nigriceps, Cacajao melanocephalus, Chiropotes satanas and Callicebus caligatus. The 14/15 hybridization pattern was present in 13 species, but not in Alouatta sara that showed a 14/15/14 pattern and Aotus nigriceps that showed a 15/14/15/14 pattern. In the majority of the species, the HSA 14 homologue retained synteny for the entire chromosome, whereas the HSA 15 homologue displayed fragmented segments. Within primates, the New World monkeys represent the taxon with the highest variability in chromosome number (2n = 16 to 62). The presence of the HSA 14/15 association in all species and subspecies studied herein confirms that this association is the ancestral condition for platyrrhines and that this association has been retained in most platyrrhines, despite the occurrence of extensive inter- and intrachromosomal rearrangements in this infraorder of Primates.

Trissomia, Tetrassomia e pentassomia do cromossomo X: relato de 11 casos / X chromosome trisomy, tetrasomy, pentasomy: report of 11 cases

Objetivo: apresentar o quadro clínico de pacientes com trissomia, tetrassomia e pentassomia do cromossomo X...

Objective: to present the clinical findings featured by patients bearing chromossome X trisomy, tetrasomy and pentasomy...

Phenotypic and behavioral variability within Angelman Syndrome group with UPD

The Angelman syndrome (AS) (developmental delay, mental retardation, speech impairment, ataxia, outbursts of laughter, seizures) can result either from a 15q11-q13 deletion, or from paternal uniparental disomy (UPD), imprinting, or UBE3A mutations. We describe here the phenotypic and behavioral variability detected in eight UPD patients out of a group of 58 AS patients studied. All of them presented developmental delay, mental retardation, ataxia, speech impairment, and frequent drooling. Only one had microcephaly, whereas in two of them the OFC (head circumference) was above the 98th percentile. The weight of all patients was above the 50th percentile, and in three of them the height was above the 90th percentile. Three were able to say a few words and to communicate by gestures. Two patients presented hyperphagia, and three presented skin picking, common features in the Prader-Willi syndrome (PWS). Four patients (4/7) had wide-spaced teeth. Five presented seizures, and two others did not manifest frequent laughter. One patient was very different from the others, as he showed a better understanding and abilities to communicate, to play video games and to draw. We suggest here that there seems to be an extreme phenotypic and behavioral variability within the UPD group, and that both typical patients and those with mental retardation, language impairment, happy disposition, and hyperactivity should be tested for AS

Genomic imprinting: genetic mechanisms and phenotypic consequences in Prader-Willi and Angelman syndromes

O segmento cromossômico 15q11-q13 é de grande interesse em Genética Humana uma vez que diversos rearranjos estruturais têm sido descritos nessa regiäo (deleçöes, duplicaçöes e translocaçöes) resultando em fenótipos diferentes como os das síndromes de Prader-Willi (PWS) e Angelman (AS), que foram as primeiras doenças humanas a serem relacionadas com a expressäo diferencial de alelos parentais (imprinting genômico). Contrário às leis de Mendel onde a herança parental da informaçäo genética näo influencia a expressäo gênica, o imprinting genômico é caracterizado por modificaçöes no DNA que produzem diferentes fenótipos dependendo da origem parental da mutaçäo. A manifestaçäo clínica da PWS aparece quando ocorre a perda de genes com expressäo exclusivamente paterna, e a AS resulta da perda do gene com expressäo exclusivamente materna. Diferentes mecanismos genéticos podem resultar em PWS ou AS como deleçöes, dissomia uniparental ou mutaçöes no processo de imprinting. Em pacientes com AS existe uma classe adicional de pacientes com mutaçäo no gene UBE3A. Estudos de pacientes com PWS e AS podem ajudar no entendimento do processo de imprinting e, assim, outras regiöes do genoma com características similares podem ser localizadas, e diferentes síndromes podem ter seus mecanismos genéticos elucidados.

Síndrome de Angelman: causa frequentemente näo reconhecida de deficiência mental e epilepsia: relato de caso / Angelman syndrome: a frequently undiagnosed cause of mental retardation and epilepsy. Case report

Os autores descrevem um caso típico de síndrome de Angelman. A paciente apresenta atraso de desenvolvimento neuropsicomotor, deficiência mental, macrostomia, dentes espaçados, convulsöes, ausência de fala, andar com a base alargada e instável, crises de risos. Os estudos citogenéticos e moleculares revelaram deleçäo do segmento 15q11q13 de origem materna, confirmando o diagnóstico clínico de síndrome de Angelman.

Macrossomia, macrocrania e incoordenaçäo motora da infância: síndrome de sotos (McKusick 11755); Estudo de 7 casos e revisäo de aspectos clínicos de 198 casos publicados / Macrosomia, macrocrania and motor disordes in childhood: sotos syndrome (McKusick 11755), report of 7 cases and review of clinical aspects of 198 report cases

Crianças com síndrome de Sotos apresentam aceleraçäo do crescimento, macrocrania, padröes acromegalóides e dificuldades iniciais no desenvolvimento neuropsicomotor. A delineaçäo da síndrome e o diagnóstico diferencial estäo baseados na avaliaçäo das características clínicas e no histórico evolutivo desses pacientes. Sete pacientes com síndrome de Sotos säo descritos, bem como revistas as características clínicas presentes em 198 pacientes da literatura. As dificuldades motoras presentes durante a primeira infância nos pacientes com síndrome de Sotos säo responsáveis pelo mau desempenho destas crianças nos testes de QI. A estimulaçäo especializada deve ser encorajada para ajustar os afetados a superarem suas dificuldades iniciais