No abstract

We report on the 46th patient with Schinzel-Giedion syndrome (SGS) and the first observation of splenopancreatic fusion in this syndrome. In the antenatal period, a male fetus was found to have bilateral hydronephrosis. Postnatally, in keeping with a diagnosis of SGS, there were large fontanelles, ocular hypertelorism, a wide, broad forehead, midface retraction, a short, upturned nose, macroglossia, and a short neck. Other anomalies included cardiac defects, widened and dense long bone cortices, cerebral ventriculomegaly, and abnormal fundi. Splenopancreatic fusion, usually encountered in trisomy 13, was found on autopsy. Schinzel-Giedion syndrome is likely a monogenic condition for which neither the heritability pattern nor pathogenesis has yet been determined. A clinical diagnosis may be made by identifying the facial phenotype, including prominent forehead, midface retraction, and short, upturned nose, plus one of either of the two other major distinguishing features: typical skeletal abnormalities or hydronephrosis. Typical skeletal anomalies include a sclerotic skull base, wide supraoccipital-exoccipital synchondrosis, increased cortical density or thickness, and broad ribs. Other highly supportive features include neuroepithelial tumors (found in 17%), hypertrichosis, and brain abnormalities. Severe developmental delay and poor survival are constant features in reported patients.

The syndrome of tetrasomy 18p has been well documented in the literature. This is typically a result of a supernumerary isochromosome 18p, that has arisen during maternal meiosis II. This report presents clinical and molecular findings in two maternal half sisters with an isochromosome 18p. The isochromosome is inferred to have arisen during meiosis in the maternal grandmother and to have undergone mitotic and meiotic recombination in the mother of JJ and AT. The abnormal cell line may be restricted to the gonad in the mother as only normal 46,XX cells were detected by cytogenetic analysis of her blood or fibroblasts and physical examination revealed only normal findings. Thus, the isochromosome, although present at fertilization, must have been lost from the majority of embryonic precursor cells. This case raises important genetic counseling issues concerning recurrence risks.