Monoallelic and biallelic variants in LEF1 are associated with a new syndrome combining ectodermal dysplasia and limb malformations caused by altered WNT signaling.

PURPOSE: LEF1 encodes a transcription factor acting downstream of the WNT-ß-catenin signaling pathway. It was recently suspected as a candidate for ectodermal dysplasia in 2 individuals carrying 4q35 microdeletions. We report on 12 individuals harboring LEF1 variants. METHODS: High-throughput sequencing was employed to delineate the genetic underpinnings of the disease. Cellular consequences were characterized by immunofluorescence, immunoblotting, pulldown assays, and/or RNA sequencing. RESULTS: Monoallelic variants in LEF1 were detected in 11 affected individuals from 4 unrelated families, and a biallelic variant was detected in an affected individual from a consanguineous family. The phenotypic spectrum includes various limb malformations, such as radial ray defects, polydactyly or split hand/foot, and ectodermal dysplasia. Depending on the type and location of LEF1 variants, the inheritance of this novel Mendelian condition can be either autosomal dominant or recessive. Our functional data indicate that 2 molecular mechanisms are at play: haploinsufficiency or loss of DNA binding are responsible for a mild to moderate phenotype, whereas loss of ß-catenin binding caused by biallelic variants is associated with a severe phenotype. Transcriptomic studies reveal an alteration of WNT signaling. CONCLUSION: Our findings establish mono- and biallelic variants in LEF1 as a cause for a novel syndrome comprising limb malformations and ectodermal dysplasia.

Supplementary suckling technique in infants less than 6 months of age with uncomplicated severe acute malnutrition: a prospective hospital-based study in armed conflict Yemen.

BACKGROUND: Globally 3.8 million of children under 6 month of age are severely wasted. In Yemen, around 20% of children under 6 months were affected by malnutrition during the armed conflict in the last 7 years. Supplementary suckling may reestablish exclusive breastfeeding in infant less than 6 months of age with Severe Acute Malnutrition (SAM). This study aimed to determine the outcomes of employing supplementary suckling technique in treatment of uncomplicated SAM infants in a conflict-affected community. METHODS: A prospective hospital-based study was carried out between January to April 19th, 2020 among randomly selected infants less than 6 months of age with SAM following breastfeeding failure. Infants' anthropometric indices were daily measured and recorded. Supplementary sulking technique was used in management with high or low protein milk-based formula supplement. Outcome was recorded as cured, died, defaulter or in nonrecovery state. RESULTS: In this study 108 infants were enrolled with a median (IQR) age of 4 (2.5-5) years and a male: female ratio of 1.4:1. After treatment, 80.6% recovered to cure, 12% defaulters, 6% died, and 2% did not respond to treatment Thirty-four infants (38.8%) gained weight with significantly increased median weight and median weight-for-age z score. The median (IQR) duration of treatment was 9 (7.5-14) days. The means of age and weight-for-length z score were correlated (r = - 0.22, p = 0.025). Duration of treatment was a predictor of outcome (OR = 1.71, 95% CI = 0.05-0.62, p < 0.001). CONCLUSION: Supplementary suckling technique for feeding infant with SAM aged less than 6 months had a positive impact on anthropometric indices with high cure rate. The younger the infant and the longer the duration of treatment, the better the outcome.

Anthropometric measurements of singleton live full-term newborns in Aden, Yemen.

BACKGROUND: Neonatal anthropometry is the single most portable, universally applicable cheap, and non-invasive technique that deals with a variety of human body measurements. The anthropometric data for newborns, infants and children reflect their general health, nutritional status, and future survival by tracking trends in growth and development over time. PATIENTS AND METHODS: The present study was conducted on 1000 Yemeni singleton live full-term newborns (37-42 weeks gestation), 488 males and 512 females during first 24 h of delivery at Al-Sadaqa Teaching Hospital, Aden, Yemen during the years 2002-2003. RESULTS: The data analysis of seven anthropometric values for 1000 Yemeni term newborns of both sexes revealed the mean birth weight and SD was 3113.04 g (±519.52), crown-heel length, head, chest, mid-arm, abdominal and calf circumferences were 48.91 (1.62), 33.78 (1.13), 32.09 (1.48), 10.09 (1.02), 30.10 (1.92), and 10.94 (1.04) respectively. The Ponderal Index was calculated with mean value of 2.65 (0.40). This study showed significant sex differences in all the anthropometric measurements principally in the birth weight (3187.66 versus 3039.04) and crown-heel length CHL (49.28 versus 48.53). (P < .001). The best cut-off point to determine LBW was calf circumference (8.5 cm), which showed the most significant correlation with birth weight (r = 0.5) followed by chest (r = 0.44) and mid-arm circumference (r = 0.41). CONCLUSIONS: This study of normal reference values will provide basic step for future standardization of Yemen anthropometric parameters to be used for accurate assessment, development and maturity of newborn births that would lead to identify newborns at risk and help in better management.

Childhood cancer in Aden, Yemen.

BACKGROUND: Cancer in children is increasingly recognized as a major and growing health problem in different developed and developing countries. In Yemen, it is still difficult to know the extent of cancer and its determinants among children. This study was conducted to determine the magnitude of childhood cancer in Aden and provide the preliminary baseline data by age and sex. METHODS: Basic epidemiologic data was retrieved from all paediatric cancer <15 years age registered in Aden Caner Registry (ACR), Yemen, from 1997 to 2006. RESULTS: The results showed a total of 483 childhood cancers <15 years age comprising 12.7% of all registered malignancies with a male to female ratio of 1.5:1. The predominant age affected was 5-9 years in (38.3%) children. The most frequent cancer among Yemeni children was leukaemia 160 (33.1%) followed by lymphoma 152 (31.5%), CNS tumors 35 (7.2%) and bone tumours 25 (5.2%). An interesting and unusual finding was the frequency of acute myeloid leukaemia twice more common in female (66.7%) than male (33.3%). Lymphoma was the most common cancer in children >5 years. An interesting comparison was the preponderance of non-Hodgkins's lymphoma over Hodgkin's disease (1.6:1) stronger in female (3:1) than male (1.25:1). Medulloblastoma was the most common CNS tumour followed by astrocytoma, an infrequent finding in childhood cancer. Osteosarcoma was the most frequent bone tumour (male:female ratio of 1.8:1). A female preponderance was noticed in chondrosarcoma that was not yet documented. The blastoma group was common in younger age group. Retinoblastoma and nephroblastoma predominated in female while neuroblastoma, hepatoblastoma and soft tissue sarcomas in male. CONCLUSION: It is concluded that there is a lower frequency of childhood cancer in Aden when compared with developed countries. It may explained by the fact that a large number of childhood cancers remain undiagnosed due to limitations of diagnostic facilities or under registration. Central paediatric hospitals should be provided with essential diagnostic and therapeutic services that should be freely available to all children with cancer.