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Two genes causing megalencephalic leukoencephalopathy with subcortical cysts (MLC) have been discovered so far. Here, we identified MLC1 and HEPACAM mutations in ten and two patients, respectively. The molecular results included an unreported inframe duplication mutation (c.929_930dupCTGCTG; p.L309dup) of MLC1 and a novel missense mutation c.293G>A (p.R98H) of HEPACAM. Further, the previously reported missense (c.278C>T; p.S93L) and the deletion/insertion (c.908_918delinsGCA; p.V303Gfs*96) were found in one and 8 patients (75 %), respectively. The 8 patients carrying the p.V303Gfs*96 shared a similar haplotype suggesting a founder effect. All mutations were in the homozygous state proving the autosomal recessive mode of inheritance. The core phenotype of macrocephaly, subcortical cysts and white matter appeared homogeneous although the patients differed in the onset, clinical course, disease severity and brain imaging findings. Our study expands the spectrum of mutations in MLC1 and HEPACAM and supports the genetic and clinical heterogeneity. Further, It confirms c.908_918delinsGCA (p.V303Gfs*96) as a founder mutation among Egyptian patients. This finding will contribute to provide targeted testing for this mutation in MLC patients in our population.

The Brachmann de Lange syndrome (BDLS), first described in its full clinical presentation by Brachmann (1916) and Cornelia de Lange (1933) is a multi-system syndrome involving congenital malformations, growth retardation and neurodevelopmental delay. We describe here twelve Egyptian cases with this syndrome with emphasis on the orodental, ear and eye abnormalities and their relation to the severity of expreseion of the disorder. The crodental anomalies were high arched palate, Iong philtrum, micrognathia, macrostomia hypoplasia of upper anterior teceth, fissured tongue macroglossia. Ear malformations were low-set large ears. Otoscopy revealed normal drum appearance. Audiogram revealed conductive, sensorineural or mixed hearing loss. Ocular manifestations were nystagmus, convergentt squint, enophthalmos, myopia 8 blue scleca. The study emphasizes certain eye, ear and crodental anomalies as diagnostic features of the BDLS which correlate with the severity of expression of the syndrome. None of the cases had chromosomal aberrations and the parental consanguinity rate was not increased thus supporting dominant mutations or minor chromosomal etiology.

Down syndrome is the most frequent of the aneuploids observed in newborn infants whose major manifestations are mental and growth retardation. The purpose of this work was to study the oral manifestations, histological and histochemical changes in gingiva of Egyptian Down syndrome children and to correlate the noted histochemical changes with the intelligence quotient and the karyotype. The study comprised 29 cases (19 males and 10 females) with a mean age of (4.673 + 2.406) and 30 control children (19 males and 11 females) with a mean age of (4.632 + 2.568). 27 cases had pure trisomy 21 and 2 cases was mosaics. General clinical and orodental examination confirmed the developmental variability of Down syndrome patients. The orodental examination showed: 1--A high susceptibility to periodontal disease. 2--Bad oral hygiene. 3--High arched palate, macroglossia, hypocalcification, fissured tongue, underdeveloped maxilla delayed eruption of the primary teeth. The histological and histochemical changes were: 1--Increased inflammatory signs in the epithelium and connective tissue of the gingiva. 2--Amorphous amyloid deposits in lamina propria of Down syndrome children, while it was absent in that of control children. It was more in low I.Q. children with fair gingival index than those with better I.Q. 3--Neutral glycoprotein was stronger in Down syndrome than that in controls. 4--Reduction in the highly acidic MPS. 5--Total protein content was increased in Down syndrome children that of their controls. 6--Acid phosphatase activity was stronger in Down syndrome than of their controls. 7--Alkaline phosphatase activity was less in Down syndrome than of their controls. These changes point to a correlation which needs further investigation in a larger number of cases.

The study comprised two cases (male & female sibs) from one family, with Lesch-Nyhan Syndrome. They were subjected to clinical evaluation, pedigree construction, uric acid estimation in blood, urates in urine, metabolic screening of blood and urine for amino acids, examination of oral cavity, histological studies of the gingiva by light and electron microscopy as well as buccal smear for Barr & Y bodies (for the female). The proband, a six years old female presented with self-mutilation, mental retardation, hyperactivity and aggression. She had bitten her index finger causing amputation of its distal phalanx. On family study her younger brother (9 months) was found to have increased uric acid and less severe neurologic involvement. The serum uric acid level of the affected female was higher. Her Barr body showed normal pattern. Oral cavity examination showed no abnormalities. Histological examination of the gingiva showed macrophages around the blood vessels. Ultrastructural studies showed more or less normal epithelium. There was collection of macrophages around the blood vessels in the sub-epithelial layer, the cytoplasm of these macrophages contained stippled cytoplasmic inclusions. The surrounding connective tissue showed thin collagen fibers with sharp delineation between the epithelial and connective tissue layers indicating poor quality of collagen. There was no histological difference between the hemizygous male and the heterozygous female. The present study indicates heterozygous expression of Lesch-Nyhan Syndrome at both the clinical and the ultrastructural levels in favour of extreme lyonization or X-chromosome deletion in the affected female. Our findings also indicate that ultrastructural studies could be sensitive indicators of abnormal uric acid metabolism. Further studies are needed to compare the phenotypic expression of hemizygotes and heterozygotes with Lesch-Nyhan Syndrome at both the clinical and ultrastructural levels.