When Gwen is twelve, her parents, suspecting her failure to show signs of normal adolescent development may be more serious than they had thought, have her tested and learn that she has Turner syndrome, a chromosomal disorder that frequently manifests in short stature, broad chest, low-set ears, amenorrhea and sterility. The diagnosis brings a new source of discord into an already somewhat dysfunctional New England family.  Gwen's mother, Paulette, prefers not to talk openly about Gwen's condition, or even, for a time, to admit it is real.  Her father, a scientist at MIT, is deeply interested in finding out more about it, but the clinical nature of his interest offends his wife.

Eventually the parents divorce, each to cope with different kinds of loneliness and alienation from Gwen and her two brothers.  One of those brothers, the designated achiever, is gay, but remains closeted for some years, in keeping with his mother's family culture.  The other, after a somewhat rebellious youth, marries a girl from blue-collar California, takes a teaching job, and eventually finds himself identifying with his son who receives a diagnosis of ADD not available during Scott's own youth.  The novel follows the individual stories of the five family members, each of whom carries his or her own burden of suffering, and brings them together during an unusual holiday gathering at the end, not for magical closure, but for a remarkable moment of retrospective understanding and opportunity for each to do some self-assessment and self-disclosure.

At the heart of the story is Gwen's "condition," recognized by all of them as the sadness that lies at the core of their family's chronic discomforts with one another.  Gwen herself finds her way into an authentic love relationship in her mid-thirties with a Caribbean diving guide she meets on a chartered excursion.  Though her mother is horrified and suspicious, and the rest of her family bemused, the experience of authentic love and friendship liberates Gwen from a history of self-defeating presumptions about her own limitations.