Hereditary multiple exostoses, macrocephaly, congenital heart disease, developmental dealy, and mental retardation in a female patient: a possible new syndrome? or new association?

Hereditary multiple exostoses [HME] or multiple osteochondromas are an autosomal dominant condition and are genetically heterogeneous. It is characterized by development of two or more cartilage capped bony outgrowths [osteochondromas] of the long bones. Osteochondromas develop and increase in size in the first decade of life, ceasing to grow when the growth plates close at puberty. HME type-I is caused by mutation in the gene encoding exostosin-1 EXT1, which maps to chromosome 8q24. Type-II is caused by mutation in the gene encoding exostosin-2 EXT2 on chromosome 11p12-p11; and type III has been mapped to a locus on chromosome 19, EXT3. we report a de novo case of HME at the Kuwait medical genetic centre [KMGC] came for consultation regarding her poor school performance. She has painless bony swellings over her extremities, macrocephaly, congenital heart disease, obesity, history of developmental delay, and moderate mental retardation. Fluorescent In Situ Hybridization [FISH] analysis done using probes specific for regions 8p22/CEP8/ and 8q24.12-8q24.13 showed delineation of two copies of normal sized chromosome 8; also Cycline D1 for 11q13 locus and CEP11, telomeric regions 11q and 11p, all showed normal signals. Telomeric 19p was used to rule out any deletion of 19p and was normal too

Prevalence and clinical manifestation of celiac disease in Down syndrome patients in Kuwait

Celiac disease is a gluten dependent immune mediated enteropathy. Several gastrointestinal and immune disorders have been found in patients with Down syndrome. The association between Down syndrome and celiac disease has been reported to be between 4-17%. We aimed to look for the Prevalence and clinical manifestation of celiac disease in down syndrome patients in Kuwait. 126 down syndrome patients who where referred to our gastroenterology unit for celiac disease screening from the period 2006 till 2008 were reviewed. Patients charts were reviewed looking for those who have positive antiendomysial antibody and required upper endoscopy to confirm the diagnosis and identifying the number of patients who were proven to have celiac disease by histopathology. Gastrointestinal signs, symptoms and the presence of autoimmune diseases in patients with down syndrome were also reviewed. Out of the 126 down syndrome patients who were screened for celiac disease three patients2.4% were found to have celiac disease. The more frequent symptoms were vague abdominal pain 29 [22.7%], followed by constipation 25 [19.5%], skin rash 10 [7.9%], abdominal distention 10[7.8%], and irritability 7 [5.6%]. Regarding autoimmune diseases hypothyroidism was the most frequent 43 [33.9%], followed by Alopecia 7[5.5%], vitiligo 3 [2.4%], diabetes type 1 2 [1.6%], hepatitis 0 [0%], and pernicious anemia 1 [0.8%].One patient had coexistence of more than one autoimmune disorder hypothyroidism, celiac disease, and juvenile rheumatoid arthritis. screening of celiac disease in Down syndrome patients will help to avoid the harmful consequences of undiagnosed celiac disease, the time interval needs to be determined so, careful evaluation and long term follow up for children with Down syndrome is to be considered in view of the possibility of coexistence of more than one autoimmune disease

Endocrinal deficits in down syndrome patients with zinc deficiency

Objectives: Overt and subclinical hypothyroidism are the most common endocrinal deficits in patients with Down syndrome. Hypozincemia in DS patients is related to some endocrinal and immunological functions. Zinc deficiency has been found to impair immune response and growth rate

The aim of this study is to evaluate the role of zinc deficiency in subclinical hypothyroidism, growth hormone and insulin like growth factor levels in DS patients before and after zinc supplementation

Results: An inverse correlation has been found between TSH and zinc levels in hypozincemic patients before therapy [p = < 0.05]. Higher TSH levels have been observed [>4.2 mlu/L] in 47% of the cases. A statistically significant difference in GH levels between hypozincemic and normozincemic patients has been found [p <0.001]. Low GH values were recorded in hypozincemic patients with DS compared to normozincemic patients. On the other hand |GF-1 levels have been found to be high in hypozincemic patients [p <0.001]. There was also a significant association between the low zinc levels and impaired thyroid function and GH values [p <0.05]. There was an improvement of thyroid function after zinc supplementation for 6 months, TSH levels became 2.72 +/- 1.64mlu/L vs. 6.2 +/- 4.02mlu/L before therapy

Conclusion: Our study shows that zinc deficiency has a remarkable effect on the thyroid function and the growth hormone in patients with DS. We recommend that our patients need further cycles of zinc supplementation to have more improvement in both thyroid functions and growth hormone

Molecular mechanisms of non-mendelian inheritance in genetic diseases

Recently identified molecular mechanisms [mitochondrial DNA mutations, genomic imprinting, uniparental disomy, unstable trinucleotide repeats] responsible for the non-mendelian patterns of some genetic diseases are reviewed. Among the diseases considered are LHON [Leber's hereditary optic neuropathy], MERRF [myoclonic epilepsy with ragged-red fibers], MELAS [mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes], Prader-Willi syndrome, Angelman syndrome, fragile-X syndrome, myotonic dystrophy, as well as others