An analysis of patients with a syndrome similar to the genetic disorder, neurofibromatosis type 1, indicates that diagnosis may be difficult because of shared clinical findings, such as certain pigmentary characteristics, according to a study in the November 18 issue of JAMA.
Neurofibromatosis type 1 (NF1), an autosomal dominant disorder affecting approximately 1 in 3,000 individuals worldwide, is characterized by multiple café au lait macules (CALMs; small areas of discoloration of the skin [light-brown]), skin-fold freckling and tumors of the nervous system. Other frequently observed features are certain bone abnormalities, short stature, macrocephaly (an abnormally large head) and learning problems, according to background information in the article. NF1 diagnostic criteria were established by the National Institutes of Health (NIH) and are widely used to make the diagnosis using information obtained from physical examination, family history, and radiologic studies. A genetically distinct but similar disorder, caused by mutations of the gene SPRED1 was recently identified (and recently named Legius syndrome). The authors write that this disorder, characterized mainly with CALMs, axillary freckling and macrocephaly, may be underestimated.
Ludwine Messiaen, Ph.D., of the University of Alabama at Birmingham, and colleagues conducted a study to determine the frequency, mutational spectrum, and phenotype of neurofibromatosis type 1-like syndrome (NFLS; Legius syndrome). The study included 23 unrelated probands (first affected family member who seeks medical attention for a genetic disorder) carrying a SPRED1 mutation identified through clinical testing, who participated with their families in a genotype-phenotype study (2007-2008). In a second cross-sectional study, 1,318 unrelated anonymous blood samples collected in 2003-2007 from patients with a broad range of signs typically found in NF1 but no detectable NF1 germline mutation underwent SPRED1 mutation analysis.
The researchers found that among 42 SPRED1-positive individuals from the clinical cohort, 20 (48 percent) fulfilled NIH NF1 diagnostic criteria based on the presence of more than 5 CALMs with or without freckling or an NF1-compatible family history. "None of the 42 SPRED1-positive individuals had discrete cutaneous or plexiform neurofibromas, typical NF1 osseous [composed of or containing bone] lesions, or symptomatic optic pathway gliomas [brain tumors]," the researchers write.