Jan. 22, 2007 Idiopathic hypogonadotropic hypogonadism (IHH) is
an inherited genetic disorder that results in impaired sexual
development due to a deficiency in a sex hormone known as GnRH.
Although individuals are thought to inherit IHH by having just
one gene defect (in any one of a number of genes), not all the
evidence supports this hypothesis, for example, not all family
members with a given gene defect have the same symptoms. In a
study that appears online on January 18 in advance of
publication in the February print issue of the Journal of
Clinical Investigation, Nelly Pitteloud and colleagues from
Massachusetts General Hospital in Boston show that in two
separate families with distinct forms of IHH (Kallman syndrome
and normosmic IHH, respectively) different combinations of
several gene defects result in different disease symptoms. In
the first family, the individual with the most severe phenotype
had mutations in two different genes (FGFR1 and NELF). By
contrast, his parents and siblings with only on