MN1 C-Terminal Truncation Syndrome

Christopher CY Mak; Jasmine LF Fung; Mianne Lee; Angela E Lin; Jeanne Amiel; Dan Doherty; Christopher T Gordon; Brian HY Chung

MN1 C-Terminal Truncation Syndrome

Review

In: GeneReviews^® [Internet]. Seattle (WA): University of Washington, Seattle; 1993.

2020 Aug 13.

Authors

Christopher CY Mak¹, Jasmine LF Fung¹, Mianne Lee¹, Angela E Lin², Jeanne Amiel³, Dan Doherty⁴, Christopher T Gordon³, Brian HY Chung¹

Book Editors

Margaret P Adam, Jerry Feldman, Ghayda M Mirzaa, Roberta A Pagon, Stephanie E Wallace, Lora JH Bean, Karen W Gripp, Anne Amemiya

Affiliations

¹ Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, University of Hong Kong, Hong Kong Special Administrative Region, China
² Professor of Pediatrics, Part-time, Department of Pediatrics, Harvard Medical School, Co-Director, Turner Syndrome Program, Co-Director, Myhre Syndrome Clinic, MassGeneral Hospital for Children, Boston, Massachusetts
³ Laboratory of Embryology and Genetics of Human Malformation, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Imagine, Paris, France
⁴ Professor of Pediatrics, University of Washington;, Seattle Children's Hospital, Seattle, Washington

PMID: 32790267
Bookshelf ID: NBK560443

Excerpt

Clinical characteristics: Individuals with MN1 C-terminal truncation (MCTT) syndrome have mild-to-moderate intellectual disability, severe expressive language delay, dysmorphic facial features (midface hypoplasia, downslanting palpebral fissures, hypertelorism, exophthalmia, short upturned nose, and small low-set ears), and distinctive findings on brain imaging (including perisylvian polymicrogyria and atypical rhombencephalosynapsis). Mild-to-moderate prelingual hearing loss (usually bilateral, conductive, and/or sensorineural) is common. Generalized seizures (observed in the minority of individuals) are responsive to anti-seizure medication. There is an increased risk for craniosynostosis and, thus, increased intracranial pressure. To date, 25 individuals with MCTT syndrome have been identified.

Diagnosis/testing: No consensus clinical diagnostic criteria for MCTT syndrome have been published. The diagnosis is established in a proband with suggestive findings and a heterozygous pathogenic variant in MN1 identified by molecular genetic testing.

Management: Treatment of manifestations: Multidisciplinary specialists to help manage developmental delay / intellectual disability, feeding issues, seizures, hearing loss, and speech and language needs, especially alternative communication.

Surveillance: Routine follow up by multidisciplinary specialists per their recommendations.

Genetic counseling: MCTT syndrome is an autosomal dominant disorder typically caused by a de novo MN1 pathogenic variant. The risk to the sibs of a proband depends on the genetic status of the proband's parents: if the MN1 pathogenic variant found in the proband cannot be detected in the leukocyte DNA of either parent, the recurrence risk to sibs is estimated to be slightly greater than that of the general population because of the possibility of parental somatic/germline mosaicism. Prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible once the MN1 pathogenic variant has been identified in an affected family member.

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