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Don’t miss patients with atypical FMR1 mutations: dysmorphism and clinical features in a boy with a partially methylated FMR1 full mutation

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Abstract

Fragile X syndrome characterized by intellectual disability (ID), facial dysmorphism, and postpubertal macroorchidism is the most common monogenic cause of ID. It is typically induced by an expansion of a CGG repeat in the fragile X mental retardation 1 (FMR1) gene on Xq27 to more than 200 repeats. Only rarely patients have atypical mutations in the FMR1 gene such as point mutations, deletions, or unmethylated/partially methylated full mutations. Most of these patients show a minor phenotype or even appear clinically healthy. Here, we report the dysmorphism and clinical features of a 17-year-old boy with a partially methylated full mutation of approximately 250 repeats. Diagnosis was made subsequently to the evaluation of a FMR1 premutation as the cause for maternal premature ovarian failure. Dysmorphic evaluation revealed no strikingly long face, no prominent forehead/frontal bossing, no prominent mandible, no macroorchidism, and a head circumference in the lower normal range. Acquisition of a driving license for mopeds and unaccompanied rides by public transport in his home province indicate rather mild ID (IQ = 58). Conclusion: This adolescent demonstrates that apart from only minor ID, patients with a partially methylated FMR1 full mutation present less to absent pathognomonic facial dysmorphism, thus emphasizing the impact of family history for a straightforward clinical diagnosis.

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Abbreviations

EEG:

Electroencephalogram

FMR1:

Fragile X mental retardation 1

ID:

Intellectual disability

OFC:

Occipitofrontal head circumference

VMI:

Developmental Test of Visual-Motor Integration

WISC-IV:

Wechsler Intelligence Scale for Children-IV

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Acknowledgments

We thank the patient and his family for their support of this publication and Konrad Schmidt for his editorial help.

Conflict of interest

None of the authors has any conflict of interest. All authors have seen and approved the manuscript. No payment was given to anyone to produce the manuscript.

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Authors and Affiliations

  1. Clinical Department of Pediatrics I, Innsbruck Medical University, Innsbruck, Austria

    Edda Haberlandt & Sibylle Zotter

  2. Division of Human Genetics, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Peter-Mayr-Str. 1, 6020, Innsbruck, Austria

    Martina Witsch-Baumgartner, Johannes Zschocke & Dieter Kotzot

Authors
  1. Edda Haberlandt
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  2. Sibylle Zotter
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  3. Martina Witsch-Baumgartner
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  4. Johannes Zschocke
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  5. Dieter Kotzot
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Corresponding author

Correspondence to Dieter Kotzot.

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Communicated by Beat Steinmann

The manuscript has not been and will not be submitted elsewhere while it is under consideration of the European Journal of Pediatrics. The first draft of the manuscript was written by the first authors.

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Haberlandt, E., Zotter, S., Witsch-Baumgartner, M. et al. Don’t miss patients with atypical FMR1 mutations: dysmorphism and clinical features in a boy with a partially methylated FMR1 full mutation. Eur J Pediatr 173, 1257–1261 (2014). https://doi.org/10.1007/s00431-014-2375-6

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  • DOI: https://doi.org/10.1007/s00431-014-2375-6

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