X-linked adrenal hypoplasia congenita: a novel <Emphasis Type="Italic">DAX1</Emphasis> missense mutation and challenges for clinical diagnosis in Africa

Adrenal hypoplasia congenita (AHC) is a rare disease. The X-linked form of AHC is caused by deletions or mutations in DAX1 gene and has a variable clinical presentation. To date, no data on X-linked AHC in central Africa are available. Here, we report a Congolese pedigree with several cases of unexplained deaths of male infants. A careful analysis of the pedigree of this family lead to the recognition of an X-linked inheritance pattern, with subsequent confirmation in a female heterozygous carrier of a DAX1 missense mutation c.1274G>T, (p.Arg425Ile).The diagnosis of this condition remains challenging in a developing country, since the manifestations of AHC overlap with those of the much more frequently occurring infections; darkening of the skin is difficult to evaluate and there is a lack of access to routine endocrinological testing. The diagnosis was eventually made based on the family pedigree, evoking an X-linked inheritance pattern. This illustrates the necessity for medical and clinical genetics to be part of the curriculum of medical school in developing countries.     

Facial dysmorphism is influenced by ethnic background of the patient and of the evaluator

The evaluation of facial dysmorphism is a critical step toward reaching a diagnostic. The aim of the present study was to evaluate the ability to interpret facial morphology in African children with intellectual disability (ID). First, 10 experienced clinicians (five from Africa and five from Europe) rated gestalt in 127 African non‐Down Syndrome (non‐DS) patients using either the score 2 for ‘clearly dysmorphic’, 0 for ‘clearly non dysmorphic’ or 1 for ‘uncertain’. The inter‐rater agreement was determined using kappa coefficient. There was only fair agreement between African and European raters (kappa‐coefficient = 0.29). Second, we applied the FDNA Face2Gene solution to assess Down Syndrome (DS) faces. Initially, Face2Gene showed a better recognition rate for DS in Caucasian (80%) compared to African (36.8%). We trained the Face2Gene with a set of African DS and non‐DS photographs. Interestingly, the recognition in African increased to 94.7%. Thus, training improved the sensitivity of Face2Gene. Our data suggest that human based evaluation is influenced by ethnic background of the evaluator. In addition, computer based evaluation indicates that the ethnic of the patient also influences the evaluation and that training may increase the detection specificity for a particular ethnic.     

Skinfold over toenail is pathognomonic for the popliteal pterygium syndrome in a Congolese family with large intrafamilial variability

We report on three related Congolese popliteal pterygium syndrome (PPS) patients concordant only for the skinfold over the toenail. Mutation analysis revealed that the three affected individuals carried a heterozygous missense mutation in the Exon 4, NM_006147.2:c.250C>T; p.Arg84Cys. This is the first molecularly confirmed PPS family from central Africa.     

Improvement of LDL-C laboratory values achieved by participation in a cardiac or diabetes disease management program.

Poor lipid control is a risk factor for cardiovascular diseases and diabetes complications. Frequently, however, patients with these diseases do not achieve blood lipid levels recommended by current standards of care. A retrospective study of 67,244 members eligible for disease management (DM) was initiated to evaluate the ability of interventions to promote improvement in low-density lipoprotein cholesterol (LDL-C) laboratory values for people with cardiovascular diseases or diabetes. The baseline trend in improving LDL-C values in the absence of DM was established. A two-year period prior to the start of the DM intervention was examined to measure the mean percent change in LDL-C values that was occurring in the population. The mean percent change observed for this pre-intervention group was then compared to the change in LDL-C values observed during the DM study period. A significant reduction in elevated LDL-C values (F-test; p < 0.0001) was observed for members who participated in the DM interventions, even when elevated LDL-C was defined as low as > or =70 mg/dL. Members with LDL-C values within threshold limits maintained these levels during the DM program. The significant reduction in elevated LDL-C values and maintenance of optimal values (< 100 mg/dL) was observed over the course of 3 years of participation in a DM program. A subset of the population also was examined to assess the impact of telephone intervention on reducing elevated LDL-C values. A significant relationship between receiving care calls and reduction in elevated LDL-C levels was observed; members who received calls achieved up to a 32.5% relative reduction in elevated LDL-C values compared to members who did not receive calls. In conclusion, these findings demonstrate the ability of DM interventions to assist a large, geographically diverse member population in reducing a clinical laboratory value.