ABSTRACT
Phelan-McDermid or 22q13.3 deletion syndrome is characterized by global intellectual disability, childhood hypotonia, severely delayed or absent speech, features of autism spectrum disorder, without any major dysmorphisms or somatic anomalies. It is typically diagnosed before adolescence and data about adult patients are virtually absent. The expression of its phenotypical characteristics appears to be linearly related to the deletion size. Here, an intellectually disabled geriatric female patient is described with a long history of challenging behaviors in whom Phelan-McDermid syndrome was demonstrated. Detailed analysis of the patient's history and functioning resulted in a psychiatric diagnosis of atypical bipolar disorder and her behavior significantly improved upon maintenance treatment with a mood stabilizing agent. The present article confirms recent findings that atypical bipolar disorder may be part of the psychopathological phenotype of Phelan-McDermid syndrome, reason why careful etiological search is warranted, also in the geriatric population.
Subject(s)
Chromosome Disorders/diagnosis , Chromosome Disorders/genetics , Aged , Butyrophenones/therapeutic use , Carbamazepine/therapeutic use , Carrier Proteins/genetics , Choline Kinase/genetics , Chromosome Deletion , Chromosomes, Human, Pair 22/drug effects , Chromosomes, Human, Pair 22/genetics , Developmental Disabilities/drug therapy , Developmental Disabilities/genetics , Developmental Disabilities/pathology , Female , Follow-Up Studies , Histone-Lysine N-Methyltransferase/genetics , Humans , Intellectual Disability/genetics , Lithium/therapeutic use , Mitochondrial Proteins/genetics , Molecular Chaperones , Muscle Hypotonia/genetics , Nerve Tissue Proteins/genetics , Phenotype , Thymidine Phosphorylase/geneticsABSTRACT
An extended analysis for loss of heterozygosity (LOH) on eight chromosomes was conducted in a series of 82 Wilms tumors. Observed rates of allele loss were: 9.5% (1p), 5% (4q), 6% (6p), 3% (7p), 9.8% (11q), 28% (11p15), 13.4% (16q), 8.8% (18p), and 13.8% (22q). Known regions of frequent allele loss on chromosome arms 1p, 11p15, and 16q were analyzed with a series of markers, but their size could not be narrowed down to smaller intervals, making any positional cloning effort difficult. In contrast to most previous studies, several tumors exhibited allele loss for multiple chromosomes, suggesting an important role for genome instability in a subset of tumors. Comparison with clinical data revealed a possible prognostic significance, especially for LOH on chromosome arms 11q and 22q with high frequencies of anaplastic tumors, tumor recurrence, and fatal outcome. Similarly, LOH 16q was associated with anaplastic and recurrent tumors. These markers may be helpful in the future for selecting high-risk tumors for modified therapeutic regimens.
