Over the past 30 years, the link between etiology and outcome has played an increasingly more central role in the fields of intellectual disability (ID) science and practice. This paper reviews the expansion of behavioral and developmental science in the field of etiology-related ID research over the past few decades, with an emphasis on the range of etiology-related research approaches that have become prominent. Methodological issues and challenges are considered, as well as new directions for etiology-specific educational approaches, treatments, and interventions.

The Central Role of Etiology in Science and Practice in Intellectual Disability

Summary: Atypical Down syndrome phenotype in a girl with 21;21 translocation trisomy: We describe a girl with microcephaly, short stature, coarse face, severe growth and developmental delay, seizures, hypertonia, bilateral flexion contractures of the knees, and a de novo 21 ;2 1 translocation trisomy 2 1 in peripheral blood lymphocytes. Fluorescence in situ hybridization (FISH) analysis confirmed the trisomy 21 translocation using whole chromosome painting probe 21 (WCP21). Chromosome analysis which was also performed on skin fibroblasts and revealed mosaicism for a translocation trisomy 21 cell line (22.3%) as well as a second cell line consisting of one normal chromosome 21 and a small ring chromosome 21 derived from the translocation 21q21q (61%) and a third line consisting of monosomy 21 (16.7%). FISH analyses by LSI21 probe for the critical (2Iq22.2-22.3) region of Down syndrome (DS) on interphase blood cells resulted with 30% two signals and 70% three signals, skin fibroblasts showed 84% single signal, 9% two signals and 7% three signals. The size of ring chromosome 21 in skin fibroblasts was very small and probably there was a large, more proximally located deletion including chromosome 21q22 band. We consider that the atypical DS phenotype of the patient originated from the small ring chromosome 21 and the monosomy 21 in the skin fibroblasts and other tissues not available for analysis. Therefore, the clinical findings of the patient were most similar to monosomy 21 mosaicism syndrome. Key-words: Down syndrome - Monosomy 21 - Mosaicism- Ring 21 INTRODUCTION Down Syndrome (DS) is the most common chromosomal disorder associated with mental retardation and typical facial features. Previous reports have indicated that most of phenotypical features can be correlated with trisomie condition of the DS 21q22.2 critical region (3, 5). In 1974, Orye and Craen (6) and later in 1982 Dallapiccola et al. (2) reported t(2 1 q2 1 q)/r[t(2 1 q2 1 q)] mosaic karyotypes in blood lymphocytes of unrelated infants with mild manifestations of DS. Avramopoulos et al. (1) presented a patient also with an atypical or mild phenotype of DS with full free trisomy 21 in blood and skin fibroblasts while placental mosaicism was present. Recently, Keppler-Noreuil et al. (4) reported a patient who had a 21;21 translocation trisomy 21 in blood cells while mosaicism in skin fibroblast cells with an atypical DS phenotype consisting of microcephaly, downslanting palpebral fissures, short stature, severe developmental delay, seizures and hypertonia. CASE REPORT A 10-years-old female patient was admitted to our unit because of dysmorphic features and severe developmental delay. She was the fourth child of non-consanguineous parents, a 45-year-old father and a 37-year-old mother, who were both in good health. She had two brothers and one sister who were all healthy. The pregnancy was uncomplicated. She was born on the 38th gestational week with intrauterine growth retardation (birth weight: 1300 g). Her psychomotor development was severely delayed; head control was gained at 12 months, she was sitting supported at 5 years, could not walk without support and could not speak any word at the age of 10 years. She had three seizures between 7 months and 5 years. Her weight, height and head circumferences were 13.5 kg (-3.6 SD), 1 03 cm (- 5.3 SD) and 44.5 cm ( Abdominal ultrasonography was normal. The cranial MRI revealed cortical atrophy and corpus callosum agenesis. …

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Atypical Down syndrome phenotype in a girl with 21;21 translocation trisomy.