Browsing by Author "Kay, T."
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- Hypomelanosis of Ito vs Pigmentary Mosaicism: a challenging diagnosisPublication . Antunes, D.; Kay, T.; Cabete, J.; Marques, B.; Brito, F.; Correia, H.; Nunes, L.Introdution: Since 1952 several case reports and case series of Hypomelanosis of Ito (HI) has described different associations with multiple extra cutaneous manifestations, being the neurological anomalies the most frequent and important ones. Methods: We report a 5-years-old girl, refered by dyschromia , minor dysmorphic features, strabism, ventricular septal heart defect and slight learning difficulties. The peripheral blood karyotype that was normal. Hypopigmented patches along Blaschko’s lines were observed. Other anomalies included a simian palm crease on right hand, persistency of fetal pads, and mild genu valgum/recurvatum. A skin biopsy for histopathological and cytogenetic studies was performed on a hypopigmented patch and a magnetic resonance imaging (MRI) of central nervous system (CNS) was requested. Results: Histopathological study of the skin was inconclusive. However, the cytogenetic study revealed the presence of mosaicism: one normal cell line and one abnormal cell line with monosomy of chromosome 18 and presence of a marker chromosome (46,XX,-18,+mar[22]/46,XX[28]) . Fluorescence in situ hybridization (FISH) technique identified the marker as a derivative of chromosome 18, comprising the centromeric region and a small portion of euchromatic material. CNS MRI was normal. Discussion: Some authors suggest that HI would be better designated as “pigmentary mosaicism”, following the hypothesis that the chromosomal abnormalities reported specifically disrupt pigmentary genes. Although numerous cases of mosaicism concerning chromosome 18 were previously described, this specific cytogenetic anomaly was not yet reported. The mild phenotype presented in this case suggests that mosaicism may have a low expression. Nevertheless, the loss genetic material in the abnormal cell line raises several questions about future outcomes, especially regarding the theoretical concern of a predisposition to certain malignancies and the difficulty of genetic counseling. This case illustrates the challenge of a diagnosis when facing a variety of phenotypes and reinforces the importance of karyotyping other tissues besides peripheral blood.
- Microarray in clinical practice – utility vs complexity. Mixed phenotype of duplication 15q11.2q13.1 and deletion 16p11.2Publication . Antunes, Diana; Rodrigues, M.I.; Carvalho, I.; Freixo, J.P.; Marques, B.; Pedro, S.; Kay, T.; Correia, H.; Castedo, S.; Nunes, L.Introduction: There’s a consensus to perform chromosomal microarray technique as first-tier clinical diagnostic test for individuals with developmental disabilities. However, given the complexity of clinical presentations, often several diagnostic methods are held before conducting microarray. Method: We report the case of a 5 year-old boy referred to Medical Genetics due to short stature, developmental disabilities and facial dysmorphic features. He was born from eutocic delivery after an uneventful pregnancy. He had psychomotor milestones delayed like sitting at 9 months and walking at 24 months, holding an immature broad-based gait. There was history of learning difficulties from both parents, and the mother has also short stature. On examination it was noted some facial dysmorphic features like high forehead, conical canines and rarefaction of the distal portion of the eyebrows. Due to the history of an episode of transient ataxia, and suspicion of an inherited metabolic disorder, he had already performed various analytical and imaging screenings, all normal. Results: Chromosomal microarray analysis revealed two pathogenic Copy Number Variants (CNV’s): 16p11.2 deletion and 15q11.2q13.1 duplication. The 15q11q13 microduplication syndrome (OMIM # 608636) is a very rare clinical entity with about 30 reported cases with maternal origin, and it is characterized by neurobehavioral disorder, hypotonia, cognitive impairment, epilepsy and short stature. The 16p11.2 microdeletion syndrome (OMIM # 613444) is also a rare clinical entity, with high penetrance, associated with obesity and developmental disabilities. Discussion: Despite the unquestionable utility of microarray, the correlation of the CNV's with the phenotype is often difficult by the rarity of these new microdeletion/duplication clinical entities. In this case the interpretation has increased difficulty because of the simultaneous existence of two distinct clinical entities. Segregation studies, which in the first step include parental analysis, are essential for genetic counseling and determining the risk of recurrence but also for a more accurate correlation genotype-phenotype.