Facial cleft

SUMOl haploinsufficiency has been linlced to a developmental defect Based on the finding that a patient with a cleft lip and palate had a mutation in the SUMOl gene locus, a mouse model was generated that had reduced SUMOl expression. Increased frequency for a cleft palate or oblique facial cleft was observed in the transgenic mice, suggesting that SUMO haploinsufficiency can lead to developmental defects. 

Trisomy 13 (Patau syndrome, 47,XY,+13 47,XX,H 13) is seen in approximately 1 in 10,000 live births. More than 90% of conceptions are lost prenatally, and more than 90% of those who survive to term do not survive to 1 year of age. Common disease features include oral-facial clefts, microphthalmia (small eyes), renal defects, and polydactyly (extra fingers). Central nervous system malformations and heart defects are common and contribute to mortality. 

The effects of exposure to organic solvents in pregnancy have been reviewed (52). There is evidence of a moderate increase in the risks of spontaneous abortion and congenital malformations, especially facial clefts. 

Engelking, L. J., Evers, B. M., Richardson, J. A., Goldstein, J. L., Brown, M. S., and Liang, G. Severe facial clefting in Insig-deficient mouse embryos caused by sterol accumulation and reversed by lovastatin. J Clin Invest 116 (2006) 2356-2365. 

The risk of foetal malformation is increased in women with epilepsy compared with the general population. Minor dysmorphic features are most frequent, but more severe forms such as facial clefts and neural tube defects are not uncommon. The two major forms of neural tube defects are (i) anence-phaly, a lethal malformation, and (ii) spina bifida—a closure defect in the spinal eolumn that may lead to paralysis of the lower limbs. The rates of malformations are about 3% with CBZ and lamotrigine (LTG), 7% with VPA, and 15% with combinations of two or more AEDs. It is probable that AEDs have several different teratogenic mechanisms. Low folate levels appear to be associated with increased risks of foetal malformations in women on AEDs. Furthermore, it has been suggested that maternal C677T MTHFR polymorphism or some abnormality related to methionine synthetase increase the risk of foetal malformation in patients on AEDs (Mills et al. 1995). 

Teratogenicity A case of bilateral oblique facial clefts and extremity anomaly has been reported following in utero exposure to EFV. Its teratogenic risk has also been reviewed [225 ]. 

Shanske AL. Bilateral obEque facial clefts and extremity anomaly in an infant after intrauterine efavirenz exposure and review of its teratogenic risk. AIDS 2012 26(14) 1775-9. 

The dominant supramolecular synthon present in these compounds is the pi-halogen dimer (PHD) interaction [22], This efficient packing motif results from two inversion-related host molecules packing such that one bromine atom from each is situated in the cleft of its V-shaped partner (Figure 3), in addition to aromatic endo, endo-facial interaction. 

Administration of fluorouracil to pregnant rats on day 14 of gestation resulted in dose-dependent growth retardation and numerous malformations in near-term fetuses, including hind limb defects and cleft palate (126). After treatment, a number of rapid biochemical and cellular alterations were detectable in embryonic hind limbs and in craniofacial and other tissues, including inhibition of thymidylate synthetase and altered cell cycle progression. In order to assess the importance of these early events in fluorouracil-induced dysmorphogenesis, embryonic mid-facial tissues and hind limbs were dissected 3 or 6 hours after administration of fluorouracil to the dam and placed in explant culture. After 5 days in culture, craniofacial explants were evaluated... 

Oral-facial-digital syndrome type 1 Lobulated tongue, median pseudocleft of lip, cleft palate, hypoplastic alae nasi, digital anomalies, mental impairment Often late onset polycystic kidney disease X-1 (311200) CXORF5... 

Phenothiazines and butyrophenones may cause various movement disturbances in man. Dystonia in children and young adults and parkinsonism or restlessness in older subjects may occur during treatment and are reversible. The facial dyskinesia which may occur in elderly subjects, especially those with evidence of brain damage, is often irreversible (see ref. 225 for review). Unlike reserpine, these substances have little effect on brain amine levels in animals. They behave as if they block amine receptors so that there is a compensatory activation of monoaminergic neurones with increased but functionally ineffective release of amines into the synaptic cleft. Thus,... 

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