ABSTRACT
Cryptic rearrangements involving the terminal regions of chromosomes are suspected to be the cause of idiopathic mental retardation in a significant number of cases. This finding highlights the necessity of a primary screening test for such chromosome aberrations. Here we present a multiplex fluorescence in situ hybridization telomere integrity assay which allows the detection of submicroscopic aberrations in the telomeric regions of all chromosomes. This novel approach identified an unbalanced cryptic translocation der(5)t(3;5)(q27;p15.3) in a family with three cases of unexplained mental retardation and dysmorphic features. The symptoms of the patients represent neither the classical dup(3q)- nor cri du chat syndrome, although all affected individuals demonstrate several features of both syndromes. The identification of two balanced translocation carriers emphasizes the significance of the telomere integrity assay for genetic counseling and prenatal diagnosis.
Subject(s)
Chromosomes, Human, Pair 3 , Chromosomes, Human, Pair 5 , In Situ Hybridization, Fluorescence , Intellectual Disability/genetics , Telomere/ultrastructure , Translocation, Genetic , Adult , Child, Preschool , Facies , Family Health , Female , Humans , Male , PedigreeABSTRACT
We report on a mother and her 5-year old son, both with a terminal deletion of the short arm of the X chromosome. By molecular genetic analysis the breakpoint was located distal to steroid sulfatase gene. The boy manifested, due to nullisomy of this region, short stature (SHOX), chondrodysplasia punctata (ARSE), and mental retardation (putative mental retardation gene MRX 49). Short stature is present in mother and son, but both also had bilateral Madelung deformity, a key finding in the Léri-Weill syndrome. We discuss the phenotype in relationship to hitherto published cases with chromosomal aberrations and contiguous gene syndromes of Xp22.3.
Subject(s)
Sex Chromosome Aberrations/diagnosis , X Chromosome , Abnormalities, Multiple/genetics , Adult , Bone and Bones/abnormalities , Child, Preschool , Chromosome Deletion , Deafness/genetics , Female , Forearm/diagnostic imaging , Homeodomain Proteins/genetics , Humans , In Situ Hybridization, Fluorescence , Male , Mental Disorders/genetics , Radiography , Seizures/genetics , Short Stature Homeobox Protein , SyndromeABSTRACT
Congenital horizontal gaze paralysis is a rare disorder which may be associated with severe scoliosis of early onset. We present the clinical findings of two sisters with this syndrome. The additional finding of a unique pericentric inversion of chromosome 12 is considered to be incidental. Every child with congenital horizontal gaze paralysis should be evaluated for a possibly associated scoliosis. If present, a diagnosis of this presumably autosomal recessive syndrome can be made with appropriate treatment and genetic counseling.
Subject(s)
Kyphosis/complications , Nuclear Family , Ocular Motility Disorders , Scoliosis/complications , Child , Family Health , Female , Humans , Infant , Ocular Motility Disorders/complications , Ocular Motility Disorders/congenitalABSTRACT
The data of 16 children who died while receiving valproate (VPA) therapy in West Germany were analyzed. Five were normally developed, 5 were receiving VPA-monotherapy, and only 2 patients were aged less than 3 years. The first clinical symptoms of impending hepatotoxicity usually included nausea, vomiting, and apathy; pathologic laboratory tests reflected liver failure. Liver histology revealed microvesicular steatosis, cell necrosis, and bile duct proliferation of varying degree. An abnormal metabolite, 4-ene-VPA, was detected in all examined patients (six of six) and persisted after drug withdrawal. The pathogenesis of fatal liver failure during VPA treatment remains unknown. World-wide, approximately 100 fatalities have been reported in relation to VPA treatment. More than 90% were aged less than 20 years, 95% developed their first symptoms within the first 6 months of treatment, and 16 were treated with VPA alone. Since it is difficult precisely to define a group at risk for fatalities with VPA, careful clinical and laboratory monitoring with a special focus on vomiting and apathy, liver enzymes, and coagulation tests seem mandatory during the first 6 months after introduction of VPA. Taking into account the considerable number of fatalities during VPA treatment, the indication for its use requires careful reevaluation.
Subject(s)
Chemical and Drug Induced Liver Injury , Valproic Acid/adverse effects , Adolescent , Child , Child, Preschool , Epilepsy/drug therapy , Epilepsy/metabolism , Female , Humans , Infant , Liver Diseases/mortality , Liver Diseases/pathology , Male , Valproic Acid/metabolism , Valproic Acid/therapeutic useABSTRACT
A five-year-old, normally developed boy who had been healthy except for an absence epilepsy prior to valproate (VPA) treatment died 16 weeks after the introduction of VPA-monotherapy due to liver failure and intractable bleeding disorder. This case emphasizes that the restriction of VPA-therapy to children of more than two years of age, on monotherapy, and without evidence of other diseases or retardation does not exclude fatal complications. Until today world-wide about 100 patients have died during VPA-treatment.
