Café au Lait Macules and Associated Genetic Syndromes

Anderson, Sharon

doi:10.1016/j.pedhc.2019.05.001

Cited by 25 publications

(11 citation statements)

References 40 publications

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“…The diagnostic difficulties of NF1 have been discussed in the recent years and has led to an international consortium that revised the diagnostic criteria: the NIH criteria were retained with some changes and supplementary new elements (the recommendations are yet unpublished) [75][76][77][78]. According to this the following changes have been recommended:…”

Section: Limitations and Future Perspectivesmentioning

confidence: 99%

Diagnostic difficulties and possibilities of NF1-like syndromes in childhood

et al. 2021

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Background Neurofibromatosis type 1 (NF1), which is caused by heterozygous inactivating pathogenic variants in the NF1, has poor phenotypic expressivity in the early years of life and there are numerous conditions, including many other tumor predisposition syndromes, that can mimic its appearance. These are collectively termed NF1-like syndromes and are also connected by their genetic background. Therefore, the NF1’s clinical diagnostic efficiency in childhood could be difficult and commonly should be completed with genetic testing. Methods To estimate the number of syndromes/conditions that could mimic NF1, we compiled them through an extensive search of the scientific literature. To test the utility of NF1’s National Institutes of Health (NIH) clinical diagnostic criteria, which have been in use for a long time, we analyzed the data of a 40-member pediatric cohort with symptoms of the NF1-like syndromes’ overlapping phenotype and performed NF1 genetic test, and established the average age when diagnostic suspicion arises. To facilitate timely identification, we compiled strongly suggestive phenotypic features and anamnestic data. Results In our cohort the utility of NF1’s clinical diagnostic criteria were very limited (sensitivity: 80%, specificity: 30%). Only 53% of children with clinically diagnosed NF1 had a detectable NF1 pathogenic variation, whereas 40% of patients without fulfilled clinical criteria tested positive. The average age at first genetic counseling was 9 years, and 40% of children were referred after at least one tumor had already been diagnosed. These results highlight the need to improve NF1-like syndromes’ diagnostic efficiency in childhood. We collected the most extensive spectrum of NF1-like syndromes to help the physicians in differential diagnosis. We recommend the detailed, non-invasive clinical evaluation of patients before referring them to a clinical geneticist. Conclusions Early diagnosis of NF1-like syndromes can help to prevent severe complications by appropriate monitoring and management. We propose a potential screening, diagnostic and management strategy based on our findings and recent scientific knowledge.

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Section: Limitations and Future Perspectivesmentioning

confidence: 99%

Diagnostic difficulties and possibilities of NF1-like syndromes in childhood

et al. 2021

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“…Individuals presenting this autosomal dominant RASopathy may have multiple dermatological anomalies such as café-au-lait macules, neurofibromas of different types with early onset at childhood and adolescence (even oral neurofibromas have been recently reported), nevus anemicus, juvenile xanthogranuloma (a rare condition of non-Langerhans cell histiocytes), and intertriginous freckling (33)(34)(35). Pigmented skin tags are found in individuals diagnosed with GH-producing hypophyseal tumors with lentiginous-like aspects which need to be differentiated from similar skin anomalies in neurofibromatosis type 1 (36). Melanocytic proliferation in neurofibromatosis type 1 may be suboptimally screened nowadays (37).…”

Section: Syndromic Contextmentioning

confidence: 99%

Skin anomalies in acromegalic patients (Review of the practical aspects)

et al. 2021

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“…CALMs are hyperpigmented, irregularly shaped, flat birthmarks typically light brown in color, but they can vary in pigment and size, from a few millimeters to several centimeters 18–21 . Morphologically, typical café-au-lait spots are described as oval, well-circumscribed, and evenly pigmented macules 21 .…”

Section: Discussionmentioning

confidence: 99%

Constitutional Mismatch Repair Deficiency Syndromes, a Neurofibromatosis 1 Mimicker That Hinders Timely Management

Mir¹,

Almudhry²,

Alotaibi³

et al. 2023

Journal of Pediatric Hematology/Oncology

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Background: Constitutional mismatch repair deficiency (CMMRD) is a rare, autosomal recessive disease caused by a biallelic germline mutation in one of the DNA mismatch repair genes (MLH1, MSH2, MSH6 and PMS2). In addition to colorectal, brain, and hematological malignancies, many additional premalignant and non-malignant features that can point toward the diagnosis of CMMRD have been reported. The report from the CMMRD consortium revealed that all children with CMMRD have café-au-lait macules (CALMs) but the number of CALMs does not reach > 5 in all CMMRD patients, which is one of the diagnostic criterions of NF1. About half of the patients with CMMRD develop brain tumors and up to 40% develop metachronous second malignancies. Methods: This is an observational retrospective case series describing five pediatric patients with CMMRD. Results: All the five patients in our cohort developed brain tumors and showed a predilection to the frontal lobe. In our cohort, multiple Mongolian spots, coloboma, obesity, CHD, dysmorphism, and clubfoot were also encountered. In all our patients, NF1 and other tumorigenic predisposing syndromes were initially suspected. Conclusion: Increasing awareness of this condition and its shared reminiscent NF1 features, particularly CALMs among child neurologists, oncologists, geneticists, and dermatologists can help uncover the tip of the iceberg of CMMRD that carries an important consequence on management.

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Café au Lait Macules and Associated Genetic Syndromes

Cited by 25 publications

References 40 publications

Diagnostic difficulties and possibilities of NF1-like syndromes in childhood

Diagnostic difficulties and possibilities of NF1-like syndromes in childhood

Skin anomalies in acromegalic patients (Review of the practical aspects)

Constitutional Mismatch Repair Deficiency Syndromes, a Neurofibromatosis 1 Mimicker That Hinders Timely Management

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