Jean Donadieu, MD, Service d’Hémato-Oncologie Pédiatrique, Hopital, Paris, provides an overview of WHIM syndrome.
WHIM syndrome is a rare, congenital primary immunodeficiency disorder associated with neutropenia that typically presents in childhood or adolescence. However, due to the heterogeneous presentation of the disease, coupled with lack of awareness of the condition, recognition and diagnosis is often delayed, sometimes even into adulthood. Consequently, WHIM syndrome may be misdiagnosed and underdiagnosed.
To an extent, the name WHIM syndrome is a misnomer. The symptoms listed in the acronym (W)arts, (H)ypogammaglobulinemia, (I)nfections, and (M)yelokathexis do not describe the most common manifestations of the disorder, and only 23% of patients present with all four symptoms comprising WHIM.
In fact, the most common symptoms in patients diagnosed with WHIM syndrome are the laboratory findings of neutropenia (98%) and lymphopenia (88%).[3] Warts were seen in only 42% of one 66-patient cohort (though in more than half in another study), hypogammaglobulinemia in 65%, and recurrent infections in 92%. Myelokathexis, revealed via bone marrow biopsy, is often used to confirm the diagnosis, along with genetic testing.
The initial clinical sign of WHIM syndrome is recurrent infection. In a survey of patients with WHIM syndrome, Geier and colleagues[3] found that recurrent infection was the first recognizable symptom in 88% of patients (most commonly bacterial respiratory infections [49%] or otitis media [23%]). Skin infections were seen initially in 13%, and HPV-related infections (including warts) were the first recognized symptom in only 2% of patients. In this survey, 96% of patients with WHIM syndrome presented their initial symptom by age 5 years; 70% presented by 1 year of age.
