Neuroimaging manifestations and genetic heterogeneity of Walker-Warburg syndrome in Saudi patients.

BACKGROUND: Walker-Warburg syndrome (WWS), an autosomal recessive disease, is the most severe phenotype of congenital muscular dystrophies. Its diagnosis remains primarily clinical and radiological. Identification of its causative variants will assist genetic counseling. We aim to describe genetic and neuroimaging findings of WWS and investigate the correlation between them. METHODS: We retrospectively reviewed the clinical, genetic and neuroimaging findings of eleven Saudi neonates diagnosed with WWS between April 2012 and December 2018 in a single tertiary care center. Correlation between neuroimaging and genetic findings was investigated. RESULTS: All patients had macrocephaly except one who had intrauterine growth restriction. Dysmorphic features were identified in nearly half of the patients. Creatine kinase levels were available in nine patients and were always elevated. Homozygous pathogenic variants were identified in all patients spanning POMT1 (n = 5), TMEM5 (n = 3), ISPD (n = 2) and POMT2 (n = 1) including one patient who had a dual molecular diagnosis of ISPD and PGAP2. On neuroimaging, all patients showed cobblestone cortex, classical infratentorial findings, and hydrocephalus. Other cerebral cortical malformations included subependymal heterotopia, polymicrogyria and open-lip schizencephaly in four, two and one patients, respectively. Buphthalmos and microphthalmia were the most prevalent orbital findings and found in all patients either unilaterally or bilaterally. CONCLUSION: WWS is a genetically heterogeneous disorder among Saudis. The case with an additional PGAP2-related phenotype exemplifies the increased risk of dual autosomal recessive disorders in consanguineous populations. MRI is excellent in demonstrating spectrum of WWS brain and orbital malformations; however, no definite correlation could be found between the MRI findings and the genetic variant.

Pattern of neonatal and postneonatal deaths over a decade (1995--2004) at a Military Hospital in Saudi Arabia.

OBJECTIVE: To describe and monitor the causes of neonatal and postneonatal deaths in the Neonatal Intensive Care Unit (NICU) over a 10-year-period. METHODS: This is a descriptive study of all infants who died in the NICU from January 1995 until December 2004 at Riyadh Military Hospital, Riyadh, Kingdom of Saudi Arabia. Data were collected prospectively on all infants admitted to NICU. The cause of death for each infant was discussed and determined by at least 2 consultant neonatologists. Deaths were classified according to the modified Wigglesworth's classification of perinatal death. RESULTS: During the study period, there were 79871 live births and 526 deaths, in which 446 (84.2%) were inborn deaths and 80 (15.8%) were outborn. Of the inborn deaths, 251 infants died between 1-6 days, 103 died between 7-27 days, and 92 died after 27 days. Lethal malformations led to death in 36%, prematurity and its complications in 42%, hypoxic ischemic encephalopathy in 5%, while other specific diagnoses, combined, led to death in 17% of the cases. CONCLUSION: Prematurity and its complications followed by congenital malformations were the leading causes of death.

Umbilical vein interleukin-6 levels in very low birth weight infants developing intraventricular hemorrhage.

To assess the relationship between perinatal infection/inflammation as reflected by umbilical vein interleukin-6 (IL-6) levels and the development of periventricular-intraventricular hemorrhage (IVH) in very low birth weight (VLBW) infants, we tested the hypothesis that VLBW infants who develop IVH have higher concentrations of IL-6 in an umbilical vein sample compared to infants without IVH. An inception cohort of 69 VLBW infants was followed from birth until discharge or death to determine the development of IVH by serial neuroultrasounds. Umbilical vein IL-6 levels were measured using commercially available ELISA kit (Endogen Laboratories, Woburn, MA) and compared in IVH and control cohorts. Twenty-two (32%) infants developed IVH, including 18 (82%) with grade I or II and 4 (18%) with grade III or IV. One of these infants also developed periventricular leukomalacia. The umbilical vein IL-6 levels were significantly elevated in infants with IVH with median value of 87 pg/ml (25th percentile value 30 pg/ml and 75th percentile value 310 pg/ml) compared with infants without IVH, with a median value of 0 pg/ml (25th percentile value 0 pm/ml and 75th percentile value 4 pg/ml) (P = 0.007). Umbilical vein IL-6 levels are elevated in neonates who subsequently develop IVH.