Reply:

We appreciate that Guerrini-Rousseau and colleagues are raising awareness for constitutional mismatch repair deficiency (CMMRD) syndrome and its phenotypical overlap with neurofibromatosis type 1 (NF-1). All 5 patients described in our article met clinical criteria for NF-1 (Table). None of the patients reported had confirmatory genetic testing; for children who meet the clinical criteria, genetic testing is not typically obtained.

For a diagnosis of NF-1, at least 2 of the diagnostic criteria should be present³

NF-1 Diagnostic Criteria	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5
Six or more café au lait macules >5 mm in greatest diameter in prepubertal individuals and >15 mm in greatest diameter in postpubertal individuals	Yes	Yes	Yes	Yes	Yes
Two or more neurofibromas of any type or 1 plexiform neurofibroma		Yes
Freckling in the axillary or inguinal regions	Yes	Yes	Yes	Yes	Yes
Optic glioma			Yes		Yes
Two or more Lisch nodules (iris hamartomas)	Yes	Yes			Yes
A distinctive osseous lesion such as sphenoid dysplasia or tibial pseudarthrosis
A first-degree relative (parent, sibling, or offspring) with NF-1 as defined by the above criteria	Yes	Yes	Unknown (adopted)
MRI findings: focal abnormal signal intensities	Yes	Yes	Yes	Yes	Yes

CMMRD is rare (200 patients reported), and our patients had none of the other diagnostic criteria of CMMRD.¹ Café au lait spots are common (up to 97%) in CMMRD, but the other clinical manifestations of NF-1 are much less frequent.² Focal abnormal signal intensities have also been reported in CMMRD.