Brain dysgenesis and congenital intracerebral calcification associated with 3-hydroxyisobutyric aciduria.

Monozygotic male twins born to nonconsanguineous parents had dysmorphic facial features, microcephaly, migrational brain disorder, and congenital intracerebral calcification. They excreted excessive amounts of 3-hydroxyisobutyric acid, a metabolite of valine, and had evidence of impaired oxidative metabolism and metabolic acidosis. The level of 3-hydroxyisobutyrate in stored samples of midtrimester amniotic fluid was found to be high. The association of 3-hydroxyisobutyric aciduria with brain dysgenesis is a newly recognized mendelian disorder; its recurrence in a family at risk is potentially avoidable by prenatal diagnosis.

Aspartylglucosaminuria in a Puerto Rican family: additional features of a panethnic disorder.

We report on 3 Puerto Rican brothers with the clinical and laboratory findings of aspartylglucosaminuria (AGU). Their parents were first cousins. The affected sibs have the "cardinal" manifestations of AGU, including developmental disabilities, progressive "coarsening" of the face, and early onset of hepatosplenomegaly. Biochemical studies showed elevated levels of urinary aspartylglucosamine and very low activity of aspartylglucosaminidase(AGA) in cultured fibroblasts. With long term follow-up, previously undescribed manifestations were noted, including radiographic evidence of spondylolysis and spondylolisthesis in early childhood and development of macro-orchidism during puberty. This family shows that AGU is not limited to individuals of Finnish background, but that the gene is panethnic in distribution and that additional changes, not previously noted, may present with advancing age.

Trisomy 18 score: a rapid, reliable diagnostic test for trisomy 18.

We developed a bedside scoring system for diagnosis of trisomy 18 in the immediate neonatal period. Points are assigned for the presence of features known to occur in trisomy 18: five points for the presence of features previously reported in 50% or more of affected infants; three points for features reported to occur in between 10% and 50% of affected individuals; and one point for features known to occur in less than 10% of infants with the disorder. Using the scoring system, we evaluated two cohorts of patients: those in whom a diagnosis of trisomy 18 was previously established (retrospective group) and those in whom the diagnosis was suspected but not yet proved (prospective group). The average score in the retrospective series (n = 25) was 96.7, and no patient scored less than 70. Twenty-two patients were evaluated prospectively; in all cases the presence or absence of trisomy 18 was correctly predicted. The average score in the 11 patients without trisomy 18 was 41.4, and all patients scored 60 or less. In the 11 patients confirmed to have trisomy 18, the average score was 94.3, with a range of 70 to 113. This scoring system is an accurate, reproducible method for predicting trisomy 18 in neonates with multiple congenital malformations.

Autosomal recessive inheritance in the Setleis bitemporal 'forceps marks' syndrome.

We present the clinical findings in two children with the Setleis bitemporal "forceps marks" syndrome. The striking features include the following: (1) bitemporal scarring, an anomaly that resembles forceps marks; (2) periorbital puffiness with wrinkling of the skin; (3) abnormalities of the eyebrows; (4) anomalies of the eyelashes; (5) flattening of the nasal bridge with a bulbous nasal tip; (6) increased mobility of the skin, associated with severely redundant facial soft tissue; and (7) normal growth and development. The evidence that suggests that this unusual syndrome is inherited in an autosomal recessive fashion includes the following: (1) seven of the patients have come from the relatively isolated towns of San Sebastian and Aguadilla in Puerto Rico; (2) two sets of affected siblings have been described, and, in both cases, the siblings' parents were normal; and (3) one of the children described herein is the product of a consanguineous mating. Although the pathogenetic mechanism is unknown, Setleis syndrome is clearly inherited as an autosomal recessive trait.