Contributed by Eric Statz; MD and Svetlana Yatsenko; MD
The patient is a young child with a history of short stature and a hypoplastic thumb that presents with cough and worsening fatigue over the last three weeks. He was born to a non-consanguineous couple via spontaneous vaginal delivery to a 42-yearl old mother. He was seen in clinic one week prior and diagnosed with acute otitis media and prescribed amoxicillin which resolved his ear pain but failed to resolve the cough. A panel including a CBC, electrolytes, BUN, creatinine, T4 and TSH, glucose, HbA1c and urine dipstick were sent. His CBC is as follows, with the rest of the panel within normal limits:
An infectious panel including EBV, CMV, HAV, HBV and HCV were sent and found to be negative. The patient was scheduled for a bone marrow biopsy which showed 20-30% cellularity, markedly decreased megakaryoblasts and no evidence of increased blasts or any other neoplastic process. Classical chromosome analysis on the bone marrow biopsy demonstrated a 46 XY karyotype. Fanconi anemia was considered in the deferential diagnosis based on the presence of bone marrow failure, dysmorphic features and developmental abnormalities. A peripheral blood sample was evaluated for DEB clastogen assay which was positive for extensive chromosome breakage as demonstrated in Figure 1.
A CGH/SNP microarray was performed on the peripheral blood sample to rule out submicroscopic chromosomal alterations and constitutional regions of homozygosity. CGH/SNP analysis was negative for chromosomal copy number alterations, but detected long stretches of homozygosity (AOH) on chromosome 16 as in Figure 2.