Puffenberger et al. (2007) studied 16 distantly related Old Order Mennonite children with a syndrome they designated PMSE for 'polyhydramnios, megalencephaly, and symptomatic epilepsy.' All affected pregnancies were complicated by polyhydramnios. Spontaneous onset of labor occurred between 25 ... Puffenberger et al. (2007) studied 16 distantly related Old Order Mennonite children with a syndrome they designated PMSE for 'polyhydramnios, megalencephaly, and symptomatic epilepsy.' All affected pregnancies were complicated by polyhydramnios. Spontaneous onset of labor occurred between 25 and 36 weeks' gestation in 12 pregnancies. All but 1 affected child had macrocephaly. Seizures started between 3 and 7 months of age in all patients. These were most commonly complex partial seizures that would occasionally spread to involve 1 or both cerebral hemispheres. All patients had severe psychomotor retardation. Four of the 16 patients had atrial septal defects and 1 developed congestive heart failure at 3 months of age. Diabetes insipidus was present in 2 patients who were formally tested, and 2 additional patients had a clinical history suggestive of an osmoregulatory defect. Two patients had bilateral nephrocalcinosis despite essentially normal urinary calcium levels. Six of the 16 children with PMSE syndrome died between ages 7 months and 6 years. Causes of death were status epilepticus in 2, hypovolemic shock secondary to diabetes insipidus, and leukemia.
Puffenberger et al. (2007) used single-nucleotide polymorphism (SNP) microarrays to investigate the genetic basis of the disorder in 7 of the 16 children with PMSE available to them for study. Autozygosity mapping was inconclusive, but closer inspection of ... Puffenberger et al. (2007) used single-nucleotide polymorphism (SNP) microarrays to investigate the genetic basis of the disorder in 7 of the 16 children with PMSE available to them for study. Autozygosity mapping was inconclusive, but closer inspection of the data followed by formal SNP copy number analyses showed that all affected patients had homozygous deletions of a single SNP (dbSNP rs721575), and their parents were hemizygous for this marker. The deleted SNP marked a larger deletion encompassing exons 9 through 13 of the LYK5 gene (608626.0001), which encodes STE20-related adaptor protein (STRAD), a pseudokinase necessary for proper localization and function of serine/threonine kinase 11 (LKB1; 602216).
Puffenberger et al. (2007) stated that developmental delay is the presenting problem for 35% of the approximately 125 Amish and Mennonite patients evaluated each year at the Clinic for Special Children in Lancaster County, Pennsylvania. They genotyped 100 ... Puffenberger et al. (2007) stated that developmental delay is the presenting problem for 35% of the approximately 125 Amish and Mennonite patients evaluated each year at the Clinic for Special Children in Lancaster County, Pennsylvania. They genotyped 100 healthy Old Order Mennonite controls for the LYK5 deletion and identified four 7-kb deletion carriers, yielding an estimated carrier frequency for the mutant allele in Lancaster County Old Order Mennonites of approximately 4%.