Syndrome, third offspring of first cousin parents. Their first and ... MADH4 (mothers against decapentaplegic, drosophila, homolog of, 4) or BMPR1A (bone ...
Clinical genetics
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due to iron storage resolving with time. Metabolic investigations and karyotype were normal for both. Analysis of these observations together with a review of previously published cases suggests that patients suffering from tricho-hepatoenteric syndrome and/or syndromic diarrhea actually present the same heterogeneous disease that has been wrongly and confusingly separated into 2 differents entities. The 5 mains signs are the same ( Low birth weight, Intractable diarrhea, hair anomaly, facial dysmorphism and immunological defect) and the cirrhosis is found inconsistently but in both groups. The acknowledgment that these two syndromes represent the same disease is a crucial step toward a better description of this syndrome, of its outcome and to set studies trying to identify a putative underlying genetic defect.
JBS patients per year ranged between 0 and 2. Numbers increased over the years, with a maximum and stable number of around 2 newborn JBS patients per year from 1998 to 2005, probably due to improved ascertainment. This renders a mean birth prevalence of JBS of 1 in 113,797 over the period 1998-2005. When also counting the uncertain cases, the birth prevalence over this period was 1 in 83,850. We conclude that, for practical purposes, a JBS birth prevalence of 1 in 100,000 can be used. This is considerably higher than the estimate of 1 in 258,000 by Flannery & Hudson in 2004. On the basis of the Hardy- Weinberg equilibrium and the relative contribution of the different genes involved in JBS, carrier frequencies can be calculated. For the AHI1 gene, that was estimated to be responsible for 7 to 16 percent of JBS cases, this results in a carrier frequency of 1 in 598 to 1 in 395.
P0147. Mild phenotype in a child with low-rate mosaic 11q deletion
M. Podralska1, W. Cichy2, E. Czkwanianc3, D. Nowakowska4, M. Teisseyre5, R. Slomski1, A. Plawski1; 1 Instytitute of Human Genetics, Poznan, Poland, 2Karol Marcinkowski University of Medical Sciences, Poznan, Poland, 3Department of Pediatrics and Gastroenterology, Institute of Polish Mother’s Memorial Hospital, Lodz, Poland, Lodz, Poland, 4Genetic Counseling Unit Cancer Center and Institute of Oncology, Warsaw, Poland, 5Department of Gastroenterology, Hepatology and Immunology, The Children’s Memorial Health Institute, Warsaw, Poland.
E. Sukarova-Angelovska, M. Kocova, N. Angelkova, G. Ilieva; Pediatric Clinic, Skopje, The former Yugoslav Republic of Macedonia.
Monosomy of the long arm of chromosome 11 is a rare structural chromosomal aberration with facial dysmorphism and severe mental retardation. Folate-sensitive fragile site of this chromosome, located at the band 11q23.3, facilitates breakage of this part of the chromosome. Distal part of the chromosome is being lost, and causes characteristic features of Jacobsen syndrome. Mosaic deletion of the chromosome 11q has rarely been reported. We report on a girl aged 2 years with slight developmental delay. Facial dysmorphism included bitemporal narrowing, prominent glabella, hypertelorism, up-slanted eyes, short upturned nose and wide-opened mouth. The height and head circumference were at the 3rd percentile curve. Short arms and narrow thorax were present. Neurological evaluation showed slight degree of hypotonia, but motor achievements were satisfactory for the age. Speech delay was present. Ultrasound examination of the heart showed atrial septal defect. Cerebral computed tomography, renal studies and hematological evaluation were normal. The karyotype was 46XX/46,XX,del(11)(q24-> qter) (90%/10%). The parental karyograms were normal. This finding suggests a postzygotic event resulting in a child with mild clinical findings of Jacobsen syndrome. The follow-up of the child and genetic counseling is needed since the mosaic cell line could be found in ovaries as well. P0148. Johanson-Blizzard Syndrome - The importance of genetic counseling and multi-disciplinary approach to rare diseases and neurodevelopmental delay B. Bozorgmehr, A. Karimi-Nejad, A. Mirblooki, M. H. Karimi-Nejad; Kariminejad-Najmabadi Pathology & Genetics Center, 14665/154, Tehran, Islamic Republic of Iran.
We are reporting a 11-month-old Iranian girl with Johanson-Blizzard Syndrome, third offspring of first cousin parents. Their first and second child died in the neonatal period due to midline scalp defect and secondary infection. We believe they were also affected with JohansonBlizzard Syndrome. This syndrome is an extremely rare ectodermal dysplastic disorder considered to be an autosomal ressecive disorder. Each clinical manifestation has different differential diagnosis so it shows the importance of genetic counseling to help the family. The proband had growth and developmental delay, short stature, microcephaly, hypoplastic alae nasi, scar of a repaired scalp defect, upsweeped hair, hypothyroidism, deafness, and malabsorption, consistent with Johanson-Blizzard Syndrome. P0149. The birth prevalence of Joubert syndrome: a population based study in the Netherlands. H. Y. Kroes, D. E. Fransen van de Putte, C. J. Ravesloot, D. Lindhout; Dept. of Medical Genetics, Utrecht, The Netherlands.
The Joubert syndrome (JBS) is a clinically variable and genetically heterogeneous developmental brain disorder with autosomal recessive inheritance. The birth prevalence of JBS, necessary for carrier frequency calculation in genetic counseling, is not clear yet. We undertook a nationwide survey of JBS in the Netherlands. Since 2002, patients were systematically ascertained prospectively and retrospectively from multiple sources. A total of 54 patients were ascertained. The date of birth ranged from 1973 to 2005. Male:female ratio was 32:22. The number of newborn
P0150. BMPR1A gene mutations status in Polish JPS patients
The Juvenile Polyposis Syndrome (JPS), OMIM 174900 is an autosomal dominant hamartoma polyposis syndrome predisposing to gastrointestinal cancer. Autosomal dominant inheritance of the disease is associated with the mutations in one of the tumor suppressor genes MADH4 (mothers against decapentaplegic, drosophila, homolog of, 4) or BMPR1A (bone morphogenetic protein receptor, type 1A). The JPS is characterized by the occurrence of juvenile polyps in colon and upper parts of the gastrointestinal tract, the average frequency of JPS is 1:100000. The polyps occurring in childhood in most are the hamartoma polyps. The solitary or not numerous and self-limited polyps are not associated with the genetic predisposition. The characteristic feature of the occurrence juvenile polyps is rectal bleeding what is an indication for further diagnostics. The JPS encompasses the cases of numerous polyps and/or a familial component. The characteristic feature of the juvenile polyps are a markedly expanded lamina propria containing dilated cystic glands, inflammatory cells, and prominent stroma with a normal overlying epithelium. The five juvenile polyposis patients were diagnosed in specialized clinics. The recognition of the JPS syndrome in 3 cases was based on observations over 100 juvenile polyps in colon and in two cases on observation over 5 juvenile polyps in colon. The entire coding sequences of the MADH4 and BMPR1A genes were sequenced by direct PCR product sequencing. The novel BMPR1A gene mutations were detected in three JPS families. The study was financed by the Ministry of Education and Science, Poland, grant number 2PO5E02630 P0151. A new case with homoplasmic mitohondrial mutation of MT-ATP-6 and MCAD M. K. Stancheva; University Children Hospital, Sofia, Bulgaria.
The authors report a 2 year and 5 months old girl from second normal pregnancy and delivery.Family history- grandmother with cerebral stroke, with delay in psychomotor development, convulsions, hypotonia, bilateral ptosis of eyelids, more pronounced at left, divergent alternating strabismus, atrophy of nervi optici, complementary chordus in left ventricle-variant of normal, hypoplasia of right ramus communicans -variant of normal, selective metabolic screening showed MCAD and investigation of mit. DNA / PCR-SBT method, showed polymorphisms, C7028T/MT-CO1/, T 1700C/MT-RNR2, T 3197C/MT-RNR 2, A1479G/ MT-CYB/, A1146G, MT ND4, G11719A/MT-ND4/, A 8860G/MT-ATP6, T9477A/MT-CO3/, T5495/MT-ND2, A16399G/D-loop/, A263G/D-loop, 309inc C/D-loop and homoplasmic mutation T8705CC in the gene of MT-ATP 6, with aminoacid change methionin with treonin, with MRI finding of delay in white matter and hiasmic atrophy.The reported child is the fifth Case in Bulgaria with mitohondrial mutation of the MT-ATP6. The mutation is not described in literature and has unknown effect on mitohondrial function.The clinical picture is common in all cases .The presence of MCAD will be further evaluated.
