Primary microcephaly is clinically variable and genetically heterogeneous. Four phenotypically distinct types of autosomal recessive microcephaly syndromes are due to different RBBP8 mutations. We report on a consanguineous Pakistani family with homozygous RBBP8 mutation c.1808_1809delTA (p.Ile603Lysfs*7) manifesting microcephaly and a distinct combination of skeletal, limb and ectodermal defects, mild intellectual disability, minor facial anomalies, anonychia, disproportionate short stature and brachydactyly, and additionally talipes in one patient.

Background Short birth intervals (SBIs) and long birth intervals (LBIs) have been shown to have serious implications for health of both mothers and their children. This study was aimed to investigate the determinants and reproductive outcome of SBI and LBI in a multiethnic Pakistani population. Methods In a cross-sectional prospective study design, 2798 women admitted in a tertiary-care hospital in Islamabad for delivery were recruited and data on second or higher birth order deliveries were collected. Birth intervals were defined as short (<24 months) and long (>36 months). The reproductive outcome was defined in terms of perinatal and neonatal mortalities, and neonatal complications. Univariate and multivariate logistic regression analyses were performed. Results Pregnancies with SBI and LBI were observed in 20% and 24% of 2798 women, respectively. Women with SBI had increased odds of perinatal death [adjusted odd ratio (AOR): 1.50] and neonatal death (AOR: 1.47) as compared to women with optimal birth intervals, while women with LBI had slightly lower odds of perinatal deaths (AOR: 0.96), but increased odds of neonatal deaths (AOR: 1.12). Further, the pregnancies with both SBI and LBI were associated with increased odds of short body length, low birth weight, small head circumference and low APGAR score. Conclusion Nearly half of all pregnancies do not have optimal birth spacing albeit there is wide heterogeneity in the distribution of BI in various Pakistani ethnicities. Pregnancies with SBI and LBI had high risk of adverse reproductive outcome. Intervention programs for maternal and child health need to emphasize optimal birth spacing.