This hereditary neurological condition is one of a group that is responsible for severe delayed development that precludes normal growth and maturation. This specific disorder is also associated with physical and hormonal abnormalities of the sex organs, both internal and external.
Infants may be small at birth and 'floppy'. Their subsequent psychomotor development is delayed. The ears are large and the palate is highly arched. The eyelids slant upward and there may be an extra fold in the eyelid. Often the infant eyes do not seem to fix on objects or follow their movement which is likely secondary to maldevelopment of the optic nerve and vision centers in the brain. Brain imaging may reveal these abnormalities.
The external genitalia are often ambiguous and may be considered to be female in origin when they occur in chromosomally (XY) male infants. Alternatively, they may regress to a micropenis configuration resembling the genitalia of females. Studies of internal sex organs in rare individuals have not located ovaries or testes although sometimes there may be a uterus.
Mutations in a specific gene seem to be responsible for this disorder. Both members of the pair must be changed (mutated). Parental couples are frequently consanguineous and when both (who are clinically normal) contribute the mutation to a child (a 25% risk for each conception) this condition can result.
The diagnosis may be suspected from the appearance of the ambiguous genitalia at birth. The presence of 'floppiness' in the infant is a general clue that the brain may not be developed fully and the combination of these two findings should lead to a full evaluation by neurologists, obstreticians, gynecologists, and pediatricians.
Usually there are severe functional deficits and children do not respond normally to social interactions. Many do not live beyond the first decade but there have been numerous exceptions.