Wolf-Hirschhorn syndrome (WHS) or 4p-deletion syndrome has been extensively described in children. Knowledge on adult WHS patients is still limited due to the small number of published cases. We present 4 adults and review the literature. The phenotype of adult WHS is in general similar to that of childhood WHS. Growth retardation, microcephaly and mental retardation are the rule in both adults and children. Facial dysmorphism also remains similar. The main difference lies in the absence of serious internal (cardiac) abnormalities in adult WHS. Mental retardation ranges from moderate to severe. The nosological overlap between WHS and Pitt-Rogers-Danks syndrome (PRDS) is discussed. More extensive data on adult WHS are needed for appropriate counselling of families with affected young children.

A 3-year-old boy was referred to the pediatric department because of unexplained extreme obesity. Height and occipitofrontal circumference were just above the 90th centile. Endocrine studies failed to show any significant abnormality. Motor and speech development were generally delayed. On clinical-cytogenetic-molecular grounds, Prader-Willi syndrome was excluded. Fragile X syndrome was diagnosed by the presence of the classical FMR-1 mutation and confirmed by cytogenetic studies, revealing 20% fragile X positive cells. We compare the clinical features in the present patient with the nine reported patients with fra(X) syndrome and extreme obesity. In pathogenesis, hypothalamic dysregulation is hypothesized. In differential diagnosis of Prader-Willi syndrome, fragile X has to be considered, especially when laboratory workup for Prader-Willi syndrome is negative. Clinical behavior can be of help.

Aspartylglucosaminuria (AGU) is a recessive autosomally inherited lysosomal storage disorder due to deficiency of the enzyme aspartylglucosaminidase (AGA). The structural gene for this human enzyme (AGA) has been assigned to the region 4q21-->qter. We determined the AGA activity in cultured fibroblasts of a girl with a 46,XX,del(4)(q33) karyotype. The results indicate that the girl is a hemizygote for AGA, permitting the assignment of human AGA to the region 4q33-->qter.