Centronucleäre Myopathie mit autosomal dominantem Erbgang

Human Genetics - For the first time in Germany cases of a “centronuclear myopathy” are described in a 14-year-old boy and his 18-year-old sister. First symptoms in both patients...     

Microsporum canis Infection in Three Familial Cases with Tinea Capitis and Tinea Corporis

We report a familial infection caused by Microsporum canis. The first two patients were a 30-year-old female and her son, a 5-year-old boy, who came in contact with a pet dog at a farm house. The boy then suffered from hair loss for 3 months. There were circular and patchy alopecia with diffuse scaling on his scalp. Meanwhile, his mother also developed patchy erythema and scaling on her face. Several weeks later, the boy’s sister, a 4-year-old girl, was noted to have inconspicuous scaly plaques in the center of her scalp. The development of tinea capitis in the two children and tinea corporis in their mother were diagnosed based on the positive KOH examination. Morphologic characteristics and sequencing of the internal transcribed spacers 1 and 2, amplified from primary culture isolates, confirmed that their infections were caused by the zoophilic M. canis. Repetitive sequence-based molecular typing using the DiversiLab system secreted enzymatic activity analysis, and antifungal susceptibility indicated that these isolates might share the same source. The boy and girl were cured by the treatment with oral itraconazole and topical naftifine–ketoconazole cream after washing the hair with 2 % ketoconazole shampoo, and their mother was successfully treated by terbinafine orally in combination with topical application of naftifine–ketoconazole cream.     

Coincidence of familial systemic lupus erythematosus and the fragile X syndrome

The coincidence of fragile X syndrome (fra(X] and systemic lupus erythematosus (SLE) in the same family is reported here for the first time. A 16-year-old boy with typical fra(X) had a severe SLE with multiple organ involvement. His 12-year-old sister of normal intelligence had circulating antinuclear antibodies and proliferative glomerulonephritis. The fra(X) was not found in her karyotype. Except for abnormalities due to immunosuppressive treatment during pregnancy, the association of SLE and chromosome abnormalities has been only reported in Klinefelter's syndrome. The possible pathogenic role of sex hormonal abnormalities due to an extra X chromosome has been suggested in the occurrence of SLE.     

The first reported cases of human cryptosporidiosis caused by Cryptosporidium hominis in Slovak Republic

Cryptosporidiosis belongs to the important parasitic infections with zoonotic potential and the occurrence in European countries is rare. The first cases of cryptosporidiosis caused by Cryptosporidium hominis detected in the Slovak republic were described here. Collection of examined humans consisted of five family members. Faecal specimens were examined by formalin sedimentation, by the Sheather??s sugar flotation and by immunochromatography and visualised by the Ziehl?CNeelsen acid fast stain. A fragment of the Cryptosporidium small subunit ribosomal RNA gene was amplified by nested polymerase chain reaction and species was determined by restriction fragment length polymorphism analysis with the endonucleases SspI and VspI. C. hominis was found in faeces of two immunocompetent siblings (a 7-year-old boy and a 2-year-old girl). The symptoms occurred only in the boy as gastrointestinal disorders lasting 5?days, and manifested by abdominal pain, an elevated body temperature (37.2?°C), mild diarrhoea, accompanied by lassitude, depression and anorexia. Ultrasonic scan revealed enlarged spleen and mezenteric lymph nodes. Microscopic examination of the stool sample revealed numerous Cryptosporidium oocysts. The DNA typing identified C. hominis subtype IbA10G2. Cryptosporidium was also detected in the boy??s sister without any complications and symptoms. Their father, mother and grandmother were parasitologically negative. The source of infection remained unknown. Human cases in present study reflect necessity of systematic attention on intestinal parasites diagnostic inclusive of cryptosporidia.     

Identification of a new mtDNA mutation (14724G>A) associated with mitochondrial leukoencephalopathy

We report a novel 14724G>A mutation in the mitochondrial tRNA glutamic acid gene in a 4-year-old boy with myopathy and leukoencephalopathy. A muscle biopsy showed cytochrome c oxidase-negative ragged-red fibers and biochemical analysis of the respiratory chain enzymes in muscle homogenate revealed partial complex I and complex IV deficiencies. The mutation, which affects the dihydrouridine arm at a conserved site, was nearly homoplasmic in muscle and heteroplasmic in blood DNA of the proband, but it was absent in peripheral leukocytes from the asymptomatic mother, sister, and two maternal aunts, suggesting that it arose de novo. This report proposes to look for variants in the mitochondrial genome when dealing with otherwise undetermined leukodystrophies of childhood.     

Trisomy for the distal third of the long arm of chromosome 19 in brother and sister

Summary Trisomy for the distal third of the long arm of chromosome 19 was observed in a 12-year-old boy and his 9-year-old sister. Both are affected by extremely severe statural and psychomotor retardation. The physical symptoms common to both are dwarfism, micro- and brachycephaly, antimongoloid slant of the eyes, hypertelorism, ptosis, short nose, short philtrum, poorly formed ears, short neck with excess skin, barrel-shaped thorax, diastasis of rectus muscles, kyphosis, sacral dimple, excess of digital arches, pedes valgi, laterally curved big toes, epilepsy and muscular hypotonia. The chromosomal anomaly was transmitted by the mother, who is the carrier of a translocation t(19;20)(19q133;20pter). In the pedigree, extending over four generations, among 30 pregnancies fathered or mothered by 5 carriers resulted in: 6 individuals with normal karyotype, 9 carriers, 2 confirmed and 2 presumptive unbalanced abnormal children, and 10 abortions.     

Characterisation of a Xp21 microdeletion syndrome in a 2-year-old boy with muscular dystrophy,glycerol kinase deficiency and adrenal hypoplasia congenita

Summary We report a 2-year-old boy with Duchenne muscular dystrophy (DMD), glycerol kinase deficiency (GK) and adrenal hypoplasia congenita (AHC). At three weeks of age, the patient was hospitalized for the first time with symptoms of hypotone dehydration because of AHC, At present, he shows severe muscular hypotonia and developmental delay. The patient and his family were referred to us for prenatal diagnosis and carrier testing in the mother of the patient and the mother's sister, respectively. The patient's DNA was examined by Southern blot and polymerase chain reaction analyses, using cDNA and genomic probes within and around the dystrophin (DYS) locus. A deletion was revealed, spanning DXS28, the whole dystrophin locus, DXS84 and DXS148, whereas DXS67, DXS68 (pter) and OTC (cen) were found to be retained. The cytogenetically visible microdeletion was also seen in the patient's mother, but not in the mother's sister or the patient's maternal grandmother. Our findings support the locus order pter-DXS67-DXS68-DXS28-AHC-GK-DMD-cen.     

Scoliosis, blindness and arachnodactyly in a large Turkish family: is it a new syndrome?

In this report we have described an affected sib in a large Turkish family who appears to have a new distinct dominantly-inherited blindness, scoliosis and arachnodactyly syndrome. The combination of clinical abnormalities in these patients did not initially suggest Marfan syndrome or other connective tissue disorders associated with ectopia lentis. The proband was a 16-year-old boy who was referred to our clinics for scoliosis. He had arachnodactyly of both fingers and toes. He had been suffering from progressive visual loss and strabismus since he was eight-years-old. His 20-year-old brother had severe kyphoscoliosis, and arachnodactyly of fingers and toes. He was 130 cm tall and was bilaterally blind. His 23-year-old sister had only eye findings but no arachnodactyly or scoliosis. His 60-year-old father had mild scoliosis, blindness and arachnodactyly and mother was normal. We performed routine mutation analyses in the genes FBN1, TGFBR1 and TGFBR2, but no mutation has been detected. Our Turkish patients are most likely affected by a hitherto unrecorded condition which is caused by an autosomal dominant gene defect with variable expression but we can not exclude multigenic inheritance. Further studies are needed to assess the contribution of sex influence to the syndrome because the female relative is less affected.     

Familial hypoadrenalism]

Congenital hypoadrenalism was diagnosed in a 18-month boy. It is suspected that hypoplasia of the adrenals is determined genetically due to the similar course and the results of autopsy in his deceased sister.     

Familial Y/22 translocation in a woman

A phenotypically normal 35-year-old woman who had a malformed fetus was found to have a Y/22 translocation. One brother as well as a sister and her three children also have the Y/22 chromosome while another sister lacks it. The problem raised by the presence of this translocated chromosome for genetic counseling, especially for prenatal diagnosis, is emphasized.     

Unequal mitotic sister chromatid exchange and different length of Y chromosomes

Summary There is wide variation in the length of the Y chromosome. In the same individual the length varies continuously and is normally distributed. We describe a boy with borderline mental retardation, gross and fine motor coordination difficulty, muscle rigidity, ptosis, clinodactyly, and a Y chromosome of different lengths in two separate cell populations. The most probable explanation of the cytogenetic finding is a mitotic unequal sister chromatid exchange of the Y chromosome.     

Detecting breast cancer

A 7-year-old boy, diagnosed as having croup, develops an upper airway obstruction due to epiglottitis during the therapy, resulting in cerebral anoxia. Pediatricians to whom the boy is referred feel that failure to consider epiglottitis in the original diagnosis constitutes negligence. The parents suspect nothing. What should the pediatricians say or do?     

Supravalvular stenosing ring of the left atrium: Case report and review of the literature

This report concerns a 3(1/2)-year-old boy who had a supravalvular stenosing ring of the left atrium that produced left ventricular inflow obstruction. Echocardiographic and angiocardiographic data are presented, along with a review of the literature and possible theories as to the origin of this lesion.     

17-Hydroxylase/17,20 lyase deficiency diagnosed during childhood

We present a case of familial 17alpha-hydroxylase/17,20 lyase (CYP17) deficiency in which the index case, a 14-year-old XX girl, led to the diagnosis of the condition in a 9-year-old XY sister. No mutations in the CYP 17 gene were found in any of the girls.     

19p13.3 aberrations are associated with dysmorphic features and deviant psychomotor development

Here, we describe 2 patients with de novo genomic imbalances of 19p13.3. Using high-resolution microarray analysis, we detected a 1.25-Mb deletion in one patient and a 0.81- Mb duplication in another. The resulting phenotypes are quite different; one is a 2-year-old boy with macrocephaly and normal growth, while the other is a 9-year-old boy with microcephaly and growth retardation since birth. Both have dysmorphic features and psychomotor developmental delay. This report gives evidence of the effect of small aberrations of chromosome 19 and describes the phenotypes arising from a duplication and deletion of the same location at 19p13.3.     

Pre-pubertal gynaecomastia as the presenting feature of late-onset 21-hydroxylase deficiency

We describe an 8-year-old boy with pre-pubertal gynaecomastia as the presenting feature of late-onset 21-hydroxylase deficiency, an association not previously reported. Although absolute oestrogen levels were not higher than previously described in 21-hydroxylase deficiency, the gynaecomastia may have arisen through a relative disproportion of the C18 to C19 steroids.     

Orbital intravascular papillary endothelial hyperplasia in a Nigerian child: a case report and review of the literature

ABSTRACT: INTRODUCTION: Intravascular papillary endothelial hyperplasia is a reactive proliferative lesion of endothelial cells in blood vessels. It typically presents as a painless, reddish purple lesion in the sites affected. The orbit remains an uncommon site of affectation of this relatively common disease. It is noteworthy that this is the first reported case, to the best of our knowledge, of orbital intravascular papillary endothelial hyperplasia in a Nigerian child. CASE PRESENTATION: The case reported here is an orbital intravascular papillary endothelial hyperplasia causing non-axial proptosis and loss of vision in a 14-year-old Nigerian boy. We describe the clinical and histological findings of intravascular papillary endothelial hyperplasia in the orbit of this 14-year-old boy. The key distinguishing features are discussed and relevant literature is reviewed. CONCLUSION: Although unusual in presentation, intravascular papillary endothelial proliferation should be considered in the list of differentials of proptosis due to mass lesion in young Nigerians and, possibly, Africans.     

Identification of novel mutations of the DAX-1 gene in patients with X-linked adrenal hypoplasia congenita

OBJECTIVE: X-linked adrenal hypoplasia congenita (AHC) is a condition clinically featuring adrenal insufficiency and hypogonadotropic hypogonadism caused by mutations of DAX-1. This study was undertaken to characterize the molecular defects of DAX-1 in 3 unrelated Korean patients with AHC. PATIENTS AND METHODS: Patient 1 is a 6-year-old boy who presented with a salt-losing adrenal crisis in the neonatal period. Patient 2 is a 3-year-old boy who manifested aspiration pneumonia and adrenal insufficiency at the age of 1 month. Patient 3 is a 7-year-old boy who developed an adrenal crisis at the age of 3 days. In each of these patients, DAX-1 was analyzed by direct DNA sequencing after polymerase chain reaction amplification of the entire coding region. RESULTS: Direct sequencing of DAX-1 revealed two novel mutations, 1156_1157delCT in patient 1 and another novel nonsense mutation W105X in patient 2. Patient 3 had complete deletion of DAX-1. In patient 3, serum transaminases and creatine kinase levels were elevated while the glycerol kinase activity of leukocytes was decreased. Markedly elevated glycerol excretion was detected by urine organic acid analysis. Patient 3 was diagnosed as Xp21 contiguous gene syndrome associated with deletions of the entire IL1RAPL, GK genes and the C-terminal region of DMD gene. CONCLUSIONS: Two novel mutations of DAX-1 were detected in 2 unrelated patients with AHC, and complete deletion of DAX-1 in a patient with Xp21 contiguous gene syndrome who also presented with glycerol kinase deficiency, Duchenne muscular dystrophy, and AHC.     

Intercalary deletions of 9q]

Two interstitial deletions of different segments of 9q are reported. The first deletion (9/11q22) was seen in an 8-year-old boy with severe psychomotor retardation and descrete facial dysmorphism. The second deletion (9q32q34) was seen in a 5-month-old boy with a very peculiar cranio-facial dysmorphism including brachycephaly, frontal bossing, a deep nasal bridge, a short nose, and absence of triradii b, c and d.     

Mosaic pericentric inversion of chromosome 2

A pericentric inversion of chromosome number 2 in mosaic with a normal cell line is reported in a 8-year-old boy associated with slight dysmorphic syndrome and moderate mental handicap.