Kleefstra syndrome: Recurrence in siblings due to a paternal mosaic mutation.

Publication date: Aug 06, 2021

Kleefstra syndrome (KS) is a rare autosomic dominant genetic disorder caused by euchromatic histone methyltransferase 1 (EHMT1) alterations. Patients mainly present with moderate to severe intellectual disability, a severe delay in/or absence of speech, autism spectrum disorder, childhood hypotonia, neuropsychiatric anomalies, and distinctive dysmorphic features. Here, we report the cases of a male and a female, two younger siblings of three, with asymptomatic parents. An EHMT1 new mutation was identified. Both presented with a typical core phenotype. Some specific features were noted, such as macrocephaly (previously reported) and enuresis (not yet described). Parental analysis identified the mutation in the mosaic state in the father. Reverse phenotyping enabled us to highlight the pauci phenotype features of inguinal hernia, azoospermia, and possible behavioral disorders. This allowed us to adapt his follow-up and genetic counseling for the family. Our three reported cases provide a new description of KS with an intragenic EHMT1 mutation, whereas in the literature most reported cases have EHMT1 deletions. Moreover, in the areas of next-generation sequencing and trio techniques with parental segregation, it is important to remain cautious about disregarding variants based on an autosomal recessive hypothesis.

Concepts Keywords
Autism Syndromes
Azoospermia 9q34 deletion syndrome
Genetic Clinical medicine
Histone Branches of biology
Siblings Dysmorphic feature


Type Source Name
disease MESH Kleefstra syndrome
disease MESH Recurrence
disease MESH genetic disorder
disease MESH intellectual disability
disease MESH autism spectrum disorder
disease MESH hypotonia
disease MESH anomalies
disease MESH macrocephaly
disease MESH enuresis
disease MESH inguinal hernia
disease MESH azoospermia

Original Article

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