Fetal alcohol spectrum disorder in Israel Senecky, Yehuda; Inbar, Dov; Diamond, Gary ...
The Israel Medical Association journal,
10/2009, Letnik:
11, Številka:
10
Journal Article
Recenzirano
Fetal alcohol spectrum disorder is a range of disabilities caused by gestational exposure to alcohol. FASD is the leading cause of preventable mental retardation and developmental disability in the ...United States, with an incidence of 1-10 per 1000 live births. FASD in Israel has yet to be examined systematically.
To evaluate professionals' experience, awareness and knowledge of FASD in Israel and their awareness of maternal consumption of alcohol, and to collect epidemiological data on the syndrome in Israel.
A short questionnaire was sent to all 43 program directors of genetic institutes (n = 14) and child developmental centers in Israel (n = 29). Four questions related to their experience and knowledge of FASD. The epidemiological survey included data from all 17 hospitals in Israel and from the two main health management organizations within the public health care system.
The response rate was 98% (n = 42). A total of 38.1% of respondents reported having diagnosed at least one case of FASD and fewer than 10% of respondents stated that the knowledge regarding FASD among physicians in Israel was adequate. Developmental pediatricians were more likely to have diagnosed at least one case as compared to geneticists. During the period 1998-2007 the diagnosis of FASD appeared in the records of only 4 patients from the total number of 17 hospitals in Israel. During the same period only six patients were diagnosed at the HMO within the public health care system.
Despite the accumulated knowledge on FASD in many countries and the increase in alcohol consumption in Israel, professionals' awareness of its potential damage is limited. Educational programs to increase physician awareness should accompany publicity campaigns warning the public of the dangers associated with alcohol consumption during pregnancy.
Nonsyndromic mental retardation (NSMR) is the diagnosis of exclusion in mentally retarded individuals without additional abnormalities. We have recently identified a protein-truncating mutation, ...G408fsX437, in the gene CC2D1A on chromosome 19p13.12 in nine consanguineous Israeli Arab families with severe autosomal recessive NSMR, and have developed a comprehensive prevention program among the at-risk population in the village. The subjects tested were healthy women who were invited to undergo the genetic screening test as a part of their routine pregnancy monitoring. One hundred and seventeen subjects reported a family history positive for mental retardation. We tested 524 pregnant or preconceptional women and found 47 carriers (approximately 1/11), whose spouses were then recommended to undergo testing. We identified eight carrier couples, who were given genetic counseling and offered prenatal diagnosis. Of all the marriages, 28.6% were consanguineous; 16.5% of the total were between first cousins. The high prevalence of the mutation can be explained both by the founder effect owing to the generally high consanguinity rate among the inhabitants of the village, and also because two families with excessive numbers of mentally retarded offspring were unacceptable as marriage partners by the rest of the families. This is the first example of the establishment of a large-scale genetic screening program for autosomal recessive NSMR, which was made possible owing to the high frequency of the specific causative mutation in this isolated population.
Autosomal dominant isolated question mark ear Shkalim, Vered; Eliaz, Noam; Linder, Nehama ...
American journal of medical genetics. Part A,
1 September 2008, Letnik:
146A, Številka:
17
Journal Article
Fragile-X syndrome is caused by an unstable CGG trinucleotide repeat in the FMR1 gene at Xq27. Intermediate alleles (51–200 repeats) can undergo expansion to the full mutation on transmission from ...mother to offspring. To evaluate the effectiveness of a fragile-X carrier–screening program, we tested 14,334 Israeli women of child-bearing age for fragile-X carrier status between 1992 and 2000. These women were either preconceptional or pregnant and had no family history of mental retardation. All those found to be carriers of premutation or full-mutation alleles were offered genetic counseling and also prenatal diagnosis, if applicable. We identified 207 carriers of an allele with >50 repeats, representing a prevalence of 1:69. There were 127 carriers with >54 repeats, representing a prevalence of 1:113. Three asymptomatic women carried the fully mutated allele. Among the premutation and full-mutation carriers, 177 prenatal diagnoses were performed. Expansion occurred in 30 fetuses, 5 of which had an expansion to the full mutation. On the basis of these results, the expected number of avoided patients born to women identified as carriers, the cost of the test in this study (U.S. $100), and the cost of lifetime care for a mentally retarded person (>$350,000), screening was calculated to be cost-effective. Because of the high prevalence of fragile-X premutation or full-mutation alleles, even in the general population, and because of the cost-effectiveness of the program, we recommend that screening to identify female carriers should be carried out on a wide scale.
Abstract Postnatal microcephaly is defined as normal head circumference at birth, which progressively declines to more than 2 standard deviations below the average for the patient’s age and sex. We ...describe four patients from three consanguineous families of Arab Bedouin origin who presented with autosomal recessive inheritance of progressive microcephaly, spasticity, thin corpus callosum, pyramidal signs, and intellectual disability. Homozygosity mapping (Human Mapping Nsp I 250K arrays, Affymetrix, Santa Clara, CA) placed the disease locus at 8q23.2-q24.12. The candidate region includes 22 known or predicted genes, including RAD21 , which is related to the cohesion complex EIF3H , which is involved in translation initiation, and TAF2 , which may be involved in intellectual disability. Identification of the causative gene in our reported family will shed light on the pathogenesis of this severe condition.
Keppen-Lubinsky syndrome (KPLBS) is a rare disease mainly characterized by severe developmental delay and intellectual disability, microcephaly, large prominent eyes, a narrow nasal bridge, a tented ...upper lip, a high palate, an open mouth, tightly adherent skin, an aged appearance, and severe generalized lipodystrophy. We sequenced the exomes of three unrelated individuals affected by KPLBS and found de novo heterozygous mutations in KCNJ6 (GIRK2), which encodes an inwardly rectifying potassium channel and maps to the Down syndrome critical region between DIRK1A and DSCR4. In particular, two individuals shared an in-frame heterozygous deletion of three nucleotides (c.455_457del) leading to the loss of one amino acid (p.Thr152del). The third individual was heterozygous for a missense mutation (c.460G>A) which introduces an amino acid change from glycine to serine (p.Gly154Ser). In agreement with animal models, the present data suggest that these mutations severely impair the correct functioning of this potassium channel. Overall, these results establish KPLBS as a channelopathy and suggest that KCNJ6 (GIRK2) could also be a candidate gene for other lipodystrophies. We hope that these results will prompt investigations in this unexplored class of inwardly rectifying K+ channels.
: Congenital circumferential skin folds can be found in individuals with no additional defects, as well as in patients with multiple congenital anomalies and developmental abnormalities. Current ...data point to etiological heterogeneity of syndromic cases. We describe a 7‐month‐old girl with a novel combination of symmetrical congenital circumferential skin folds, dysmorphic features, and multiple congenital abnormalities. Examination of the patient revealed symmetrical congenital circumferential skin folds and dysmorphic features, as well as multiple congenital anomalies including nasal pyriform aperture stenosis, ventricular septal defect, absent spleen, camptodactyly, and severe psychomotor retardation. Skin biopsy demonstrated subcutaneous fat extending into the superficial and deep reticular dermis. Sequencing of the CDON, SHH, ZIC2, SIX3, and TGIF genes (associated with holoprosencephaly) did not disclose pathogenic alterations. Extensive review of previously described cases of syndromic congenital circumferential skin folds did not reveal a similar combination of clinical and histopathological findings.
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