Perinatal lethal form of Gaucher's disease presenting with hemosiderosis.

A term infant with hydrops fetalis presented with hypotonia, massive splenomegaly, renal failure, and severe hyperferritinemia. Multiple organ failure, myoclonus, and opisthotonus ensued and she died at 15 days of age. High rounded forehead, large open fontanel, and a small recessed chin led to initial premortem diagnosis of Zellweger syndrome, but her plasma profile of long chain fatty acid was normal. Her subsequent clinical course and findings of postmortem examinations were consistent with perinatal lethal form of Gaucher's disease (PLGD). The diagnosis was confirmed by deficiency of enzyme beta-glucocerebrosidase in white blood cells and in cultured fibroblasts. In addition to the crossover features of Zellweger phenotype, this infant exhibited a number of unusual features including, severe hyperferritinemia, rapid progression of splenomegaly, and absence of icthyosis.

Maternally inherited mitochondrial cardiomyopathy associated with a C-to-T transition at nucleotide 3303 of mitochondrial DNA in the tRNA(Leu(UUR)) gene.

Disorders associated with mitochondrial DNA (mtDNA) mutations are usually dominated by involvement of the nervous system and skeletal muscle (hence the term "mitochondrial encephalomyopathies"). However, considering the high dependence of the heart on oxidative metabolism, it is not surprising that myocardial dysfunction is often a prominent feature in these disorders, either as isolated cardiomyopathy or as part of a multisystem mitochondrial syndrome. We report an infant with a maternally inherited C-to-T transition at nucleotide 3303 of mtDNA in the tRNA(Leu(UUR)) gene; this is the second kindred with cardiomyopathy identified to have this mutation of mitochondrial DNA. A brief review of other mitochondrial DNA defects is also included.

3C (cranio-cerebello-cardiac) syndrome: a recently delineated and easily recognizable congenital malformation syndrome.

We report on two cases of 3C (cranio-cerebello-cardiac) syndrome. At least five previous cases are known. This recently delineated malformation syndrome is characterized by congenital anomalies of the skull, hindbrain, and heart. The anomalies include a high and prominent forehead, a hypoplastic vermis and posterior fossa cyst with or without hydrocephalus, and an atrial or atrio-ventricular septal defect with or without other heart anomalies. Most patients show a postnatal growth retardation, as well as a mild to moderate psychomotor retardation. Early death is usually in association with severe congenital heart defect. Aside from two affected sisters, the other reported cases (four girls and one boy) are sporadic cases; thus, a possible genetic nature and inheritance mode remain uncertain. Nonetheless, the possibility of an autosomal recessive mode of inheritance should be considered in the genetic counselling.

Identification, counselling, and outcome of two cases of prenatally diagnosed supernumerary small ring chromosomes.

De novo supernumerary small ring chromosomes have mainly been reported in pediatric patients with clinical abnormalities, thus, there may be bias of ascertainment. Reports on prenatally diagnosed cases with postnatal follow-up are rare. With the availability of chromosome specific alpha-satellite centromeric probes, the interest in these previously unidentifiable supernumerary small ring chromosomes has been rekindled [Callen et al.: J Med Genet 27: 155-159, 1990; Callen et al.: Am J Hum Genet 48:769-782, 1991; Callen et al.: Am J Med Genet 43:709-715, 1992]. We report on 2 prenatal diagnosis cases, where a ring was noted in 25 and 60% of the amniocytes, respectively. The initial G- and C-banding in Case 1 allowed an assumption of a chromosome 1 origin of the extra chromosome. This was confirmed by fluorescence in situ hybridization (FISH) studies using the appropriate probes. No similar initial assumption could be made in Case 2; thus, random trials with multiple probes were performed. A chromosome 19 origin in Case 2 was eventually concluded. The large amount of C-band positive material on the extra chromosome and the normal level 2 fetal ultrasound examination suggested a favorable outcome in both cases, but the possibility of mental retardation could not be ruled out. An empiric risk figure with regard to prenatally diagnosed de novo supernumerary small ring chromosomes is not available. Although the decision making processes of the parents were different, they both decided to continue the pregnancy. At age 9 months and 1 1/2 years both children, a girl and a boy, showed normal growth and development.