Relaxation of insulin-like growth factor 2 imprinting and discordant methylation at KvDMR1 in two first cousins affected by Beckwith-Wiedemann and Klippel-Trenaunay-Weber syndromes.

Beckwith-Wiedeman syndrome (BWS) and Klippel-Trenaunay-Weber syndrome (KTWS) are different human disorders characterized, among other features, by tissue overgrowth. Deregulation of one or more imprinted genes located at chromosome 11p15.5, of which insulin-like growth factor 2 (IGF2) is the most likely candidate, is believed to cause BWS, whereas the etiology of KTWS is completely obscure. We report a case of BWS and a case of KTWS in a single family. The probands, sons of two sisters, showed relaxation of the maternal IGF2 imprinting, although they inherited different 11p15.5 alleles from their mothers and did not show any chromosome rearrangement. The patient with BWS also displayed hypomethylation at KvDMR1, a maternally methylated CpG island within an intron of the KvLQT1 gene. The unaffected brother of the BWS proband shared the same maternal and paternal 11p15.5 haplotype with his brother, but the KvDMR1 locus was normally methylated. Methylation of the H19 gene was normal in both the BWS and KTWS probands. Linkage between the insulin-like growth factor 2 receptor (IGF2R) gene and the tissue overgrowth was also excluded. These results raise the possibility that a defective modifier or regulatory gene unlinked to 11p15.5 caused a spectrum of epigenetic alterations in the germ line or early development of both cousins, ranging from the relaxation of IGF2 imprinting in the KTWS proband to disruption of both the imprinted expression of IGF2 and the imprinted methylation of KvDMR1 in the BWS proband. Analysis of these data also indicates that loss of IGF2 imprinting is not necessarily linked to alteration of methylation at the KvDMR1 or H19 loci and supports the notion that IGF2 overexpression is involved in the etiology of the tissue hypertrophy observed in different overgrowth disorders, including KTWS.

Mild phenotype associated with an interstitial deletion of the long arm of chromosome 1.

We report on a 21 month old child referred to us because of facial dysmorphism and psychomotor retardation. The patient's phenotype was characterised by a wide and receding forehead, broad nasal bridge, redundant retronuchal skin, low set and poorly shaped ears, micrognathia, and small hands and feet. High resolution R and G banding karyotype analysis of peripheral blood lymphocytes showed an interstitial deletion of the long arm of chromosome 1 spanning bands q22 to q24. The cytogenetic results were confirmed by molecular analysis. The phenotype observed in our patient was relatively milder than those reported in other patients with an interstitial deletion of chromosome 1q.

Molecular and cytogenetic characterization of a recurrent unbalanced translocation (4;21)(p16.3;q22.1): relevance to the Wolf-Hirschhorn and Down syndrome critical regions.

We report on an aneuploidy syndrome due to the unbalanced segregation of a familial translocation (4;21)(p16.3;q22.1) causing a partial 4p monosomy and a partial 21q trisomy. The three affected children presented with severe failure to thrive, short stature, microcephaly, profound hypotonia, and mental retardation. The face, very similar in the three children, is characterized by frontal bossing, upslanting of the palpebral fissures, short nose, and deep set ears, giving the overall appearance of the Down syndrome. The molecular study has defined the aneuploid segment on both 4p and 21q. Most of the Down syndrome critical region was found to the trisomic, while only part of the candidate Wolf-Hirschhorn syndrome critical region was deleted, suggesting that this region is not critical for the major malformations characteristic for WHS.

Cutis verticis gyrata--mental deficiency syndrome: a patient with drug-resistant epilepsy and polymicrogyria.

We report a case of cutis verticis gyrata-mental deficiency syndrome (CVG-MD) which was associated with drug-resistant epilepsy and bilateral occipital polymicrogyria. Genetic analysis showed an increased number of breaks at the 3p14 and 16q23 sites. We hypothesize that a deleterious factor acting at a critical period of intrauterine development could result in the cerebral malformation and in the development of CVG. Neuroradiological investigation is warranted in cases of CVG-MD.

Prenatal ultrasound diagnosis of Roberts syndrome in a family with negative history.

A case is presented in which the ultrasonographic detection of multiple congenital anomalies led to the diagnosis of Roberts syndrome in the fetus of a woman with a negative family history. The fetus had bilateral cleft lip and palate, bilateral amesomelia with ectrodactyly, a complex congenital heart disease and intrauterine growth retardation. These malformations are frequent in Roberts syndrome and, therefore, an amniocentesis was performed to detect the cytogenetic marker of this syndrome, premature centromere separation. This phenomenon could not be detected in metaphases from amniocytes, but it was present in peripheral lymphocytes cultured at birth. The clinical implications of these findings are discussed. Furthermore, to our knowledge, this represents the first case in which the suspicion of Roberts syndrome was raised by ultrasound in a family with a negative family history.

Current treatment approaches to obsessive-compulsive disorder.

The two most useful treatments in obsessive-compulsive disorder are pharmacotherapy with potent serotonin reuptake-blocking agents and behavioral techniques, such as exposure and response prevention. Based on the authors' cumulative clinical experience, it is suggested that patient education, cognitive therapy, and psychodynamic psychotherapy are helpful adjuncts during various treatment stages of obsessive-compulsive disorder. The patient's strengths and knowledge of the illness can be used by the nurse-therapist to determine the implementation and timing of these therapeutic measures. Specific behavioral and cognitive techniques that may be useful in treating specific symptoms of obsessive-compulsive disorder are highlighted. Suggestions for future nursing research are outlined.

A malformed girl with a de novo proximal 6q deletion.

An additional case of interstitial deletion of chromosome 6, the first with breakpoints in q12 and q14, is reported. The female infant was the malformed first child of young, healthy parents. A review of proximal 6q deletions is made.

Cytogenetic study of a cell line of human penile cancer.

A cell line of penile cancer from a 60-year-old Ugandan black patient has been studied by the authors. Transmission and scanning electron microscopy showed a large number of blebs and microvilli at cell surface; desmosomes were evident at TEM. Cytogenetic investigation (R-, C-, Nor-banding) showed the frequent presence of some markers: del(1p),del(1q),iso(3q),der(4),del(8p),11q+, t rob(13;14), 14p+, t rob(21;21). The epidemiology, geographical distribution, and aetiological role of human papilloma virus type 16 and herpes simplex type 2 are discussed.

Double independent balanced translocation in a girl with mild phenotypical stigmata.

A case of de novo double independent balanced translocation t(1;7)(q44;q22), t(8;10)(q22;q26) in a girl with mild phenotypical stigmata is reported. Beside hyposomia with retarded bone age and slightly dysmorphic ear, no other abnormality was detectable and the psychomotor development was normal. A review of the similar casuistry in literature is made.

Expression of the autosomal folate-sensitive fragile sites in ten kindreds with Martin-Bell syndrome.

The authors analyse the expression of all the folate-sensitive fra sites in a sample of 24 male patients with Martin-Bell syndrome (MBS) and their 12 mothers distributed in 10 kindreds. The cytogenetic results are compared with that of a control group, constituted by 8 unrelated normal subjects. Except for the fra Xq27, there was no autosomal folate-sensitive fra site significantly more expressed in patients with MBS than in the control group. On the basis of the present cytogenetic sample of about 6 500 R-banded mitoses, a list of all the in vitro folate-sensitive fra sites and their relative frequencies is given.