Limb malformations with associated congenital constriction rings in two unrelated Egyptian males, one with a disorganization-like spectrum and the other with a probable distinct type of septo-optic dysplasia.

In this report, we describe two unrelated Egyptian male infants with limb malformations and constriction rings. The first case is developing normally but has severe limb anomalies, congenital constriction rings, scoliosis because of vertebral anomalies, a left accessory nipple, a small tumor-like swelling on his lower back with tiny skin tubular appendages, a hypoplastic scrotum, and an anchored penis. The second case is developmentally delayed with limb malformations, congenital constriction rings, a lumbar myelomeningeocele, hemangioma, and tiny tubular skin appendages on the back.

Dysmorphology of Barth syndrome.

Barth syndrome is an X-linked recessive condition caused by defective remodelling of cardiolipins in mitochondrial membranes because of mutations in the tafazzin (TAZ1/G4.5) gene located at Xq28. The cardinal features of Barth syndrome are cardiac and skeletal myopathy and neutropaenia, reported in the initial description of this condition by Barth et al.

Expression patterns of S100 proteins in melanocytes and melanocytic lesions.

S100 proteins are differentially expressed in tumours of epithelial origin. Little is known about their expression in melanocyte-derived tumours of neuroectodermal origin. We have analysed the expression of some S100 proteins in this line of lesions using SAGE Genie informatics, cell culture and human tumour tissue.

Psycho-social counselling in predictive genetic testing for cancer: the association between number of supportive sessions and client characteristics as assessed by psycho-social workers.

Given the increased demand on genetic services, it is important to identify clients who may require relatively more extensive psychosocial support. This paper describes which client characteristics, as assessed in the first psycho-social counselling session, were associated with requiring relatively more psycho-social support (> or = 3 sessions) in the process of predictive testing for cancer. The study population consisted of 244 counselees for hereditary cancer.

Update of the Pompe disease mutation database with 107 sequence variants and a format for severity rating.

Pompe disease was named after the Dutch pathologist Dr JC Pompe who reported about a deceased infant with idiopathic hypertrophy of the heart. The clinical findings were failure to thrive, generalized muscle weakness and cardio-respiratory failure. The key pathologic finding was massive storage of glycogen in heart, skeletal muscle and many other tissues.

De Barsy syndrome: a review of the phenotype.

De Barsy syndrome is a rare, autosomal recessive syndrome characterised by a progeria-like appearance with distinctive facial features and cutis laxa. Ophthalmological, orthopaedic and neurological abnormalities are also typically present. The syndrome was first described by de Barsy et al.

Regional deletion and amplification on chromosome 6 in a uveal melanoma case without abnormalities on chromosomes 1p, 3 and 8.

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Loss of the long arm and gain of the short arm of chromosome 6 are frequently observed chromosomal aberrations in UM, together with loss of chromosome 1p36, loss of chromosome 3 and gain of chromosome 8. This suggests the presence of one or more oncogenes on 6p and tumor suppressor genes at 6q that are involved in UM development.

A new syndrome with noncompaction cardiomyopathy, bradycardia, pulmonary stenosis, atrial septal defect and heterotaxy with suggestive linkage to chromosome 6p.

We report a three-generation family with nine patients affected by a combination of cardiac abnormalities and left isomerism which, to our knowledge, has not been described before. The cardiac anomalies include non-compaction of the ventricular myocardium, bradycardia, pulmonary valve stenosis, and secundum atrial septal defect. The laterality sequence anomalies include left bronchial isomerism, azygous continuation of the inferior vena cava, polysplenia and intestinal malrotation, all compatible with left isomerism.

Osteocraniostenosis: a further case report documenting the antenatal findings.

Osteocraniostenosis is a rare, lethal skeletal dysplasia with a distinctive phenotype and diagnostic X-ray findings. We present a case of an infant who was antenatally detected to have dysmorphic facial features as early as 22 weeks of gestation. Subsequent postnatal investigations confirmed the diagnosis of osteocraniostenosis.

Chromosome 7 aberrations in a young girl with myelodysplasia and hepatoblastoma: an unusual association.

We report a 30-month-old female with intrauterine growth retardation, postnatal failure to thrive, pancytopoenia and myelodysplasia with monosomy 7 in the marrow. The child succumbed to overwhelming sepsis, following a bone marrow transplant to facilitate chemotherapy for metastatic hepatoblastoma--a tumour that has not been previously reported in myelodysplasia syndromes. Cytogenetic, molecular and microarray analysis of peripheral blood, skin fibroblasts and bone marrow revealed unusual results, suggestive of somatic chromosome instability.

Congenital melanocytic naevus with associated neurofibroma and schwannoma-like change.

Congenital melanocytic naevus and neurofibromatosis type 1 are distinct clinical entities. A diagnosis of neurofibromatosis is difficult to make in the presence of a congenital melanocytic naevus because nodules may arise in the naevus that have similar histopathological appearances to neurofibromata. A case is reported where nodules arising from a naevus were examined histologically and were found to have neurofibroma and schwannoma like elements but strong positivity for S100 protein in keeping with dermal melanocytes.

Isochromosome 20p associated with multiple congenital abnormalities.

A second case of tetrasomy 20p due to an additional isochromosome 20p is reported. This resulted in a spontaneous intrauterine death with multiple congenital abnormalities. In keeping with the previous report, the foetus had poor ossification resulting in multiple long bone fractures.

Epigenotyping as a tool for the prediction of tumor risk and tumor type in patients with Beckwith-Wiedemann syndrome (BWS).

Objectives: Patients with Beckwith-Wiedemann syndrome (BWS) have a risk of 7.5% to 10% of developing childhood tumors, 60% of which are Wilms' tumors. Aberrant methylation of two distinct clusters of imprinted genes on chromosome 11p15 is detected in approximately 70% of BWS cases.

Successful pregnancies and fatherhood in familial amyloidotic polyneuropathy (FAP Val30Met) patients with liver transplantation.

For familial amyloidotic polyneuropathy (FAP) patients, several problems regarding reproduction are present. For males, erectile dysfunction and retrograde ejaculation are well known complications of the disease In addition, the risk of transferring a fatal disease to their offspring is a matter of concern for the patients. For transplanted fertile patients, the risk of side effects of immunosupression therapy causing congenital malformations must be addressed, and for female patients the additional risk of complications during pregnancy and delivery is a case of concern.

The RAS-BRAF kinase pathway is not involved in uveal melanoma.

An activating mutation has been recently observed in cutaneous melanoma in a downstream component of RAS-BRAF. The most common mutation, occurring in 80% of cutaneous melanoma samples, is a T-to-A transition resulting in a single amino acid substitution (V599E). Since cutaneous and uveal melanoma (UM) have a common origin, we aimed to establish whether activation of the BRAF proto-oncogene is also an important factor in the development of UM.

VATER--tibia aplasia association: report on two patients.

We report two patients with oesophageal atresia, tracheo-oesophageal fistula and unilateral tibial aplasia. The karyotype in both patients was normal and both cases were sporadic. The congenital defects of the children can be regarded as an uncommon variant of VA(C)TER(L) association.

Abnormal nuclear shape in solid tumors reflects mitotic instability.

Abnormalities in nuclear morphology are frequently observed in malignant tissues but the mechanisms behind these phenomena are still poorly understood. In this study, the relation between abnormal nuclear shape and chromosomal instability was explored in short-term tumor cell cultures. Mitotically unstable ring and dicentric chromosomes were identified by fluorescence in situ hybridization at metaphase and subsequently localized in interphase nuclei from five malignant soft tissue tumors.

Cytogenetic heterogeneity and clonal evolution in synchronous bilateral breast carcinomas and their lymph node metastases from a male patient without any detectable BRCA2 germline mutation.

Two synchronous bilateral breast carcinomas and their matched lymph node metastases from a 70-year-old man were cytogenetically analyzed. All four tumors were near-diploid, and except for the primary tumor from the right breast, had a 45,X,-Y clone in common. The loss of the Y chromosome was, however, common to all four tumors, whereas metaphase cells from peripheral blood lymphocytes showed a normal 46, XY chromosome complement.

Autosomal dominant myopathy: missense mutation (Glu-706 --> Lys) in the myosin heavy chain IIa gene.

We here report on a human myopathy associated with a mutation in a fast myosin heavy chain (MyHC) gene, and also the genetic defect in a hereditary inclusion body myopathy. The disorder has previously been described in a family with an "autosomal dominant myopathy, with joint contractures, ophthalmoplegia, and rimmed vacuoles." Linkage analysis and radiation hybrid mapping showed that the gene locus (Human Genome Map locus name: IBM3) is situated in a 2-Mb region of chromosome 17p13, where also a cluster of MyHC genes is located.

A single Na(+) channel mutation causing both long-QT and Brugada syndromes.

Mutations in SCN5A, the gene encoding the cardiac Na(+) channel, have been identified in 2 distinct diseases associated with sudden death: one form of the long-QT syndrome (LQT(3)) and the Brugada syndrome. We have screened SCN5A in a large 8-generation kindred characterized by a high incidence of nocturnal sudden death, and QT-interval prolongation and the "Brugada ECG" occurring in the same subjects. An insertion of 3 nucleotides (TGA) at position 5537, predicted to cause an insertion of aspartic acid (1795insD) in the C-terminal domain of the protein, was linked to the phenotype and was identified in all electrocardiographically affected family members.

Monoclonal origin of endometriotic cysts.

Endometriosis-endometrial tissue in an ectopic site outside the uterus-is one of the most common gynecologic disorders. The pathogenesis of this disease is controversial; the two major theories implicate either metaplasia or metastatic spread. In the ovary, endometriosis sometimes appears as endometriotic cysts.