2q23.1 microdeletion – 3 families demonstrate significant variability of symptoms

Tadros S, Wang R, Waters JJ, et al. “Inherited 2q23.1 microdeletions involving the MBD5 locus”. Molecular Genetics and Genomics Medicine 2017, v. 5, 608-613.

2q23.1 microdeletion – or a deletion within the q23.1 region of chromosome 2 – is known to cause a number of symptoms, such as intellectual disability, developmental delay, seizures, behavioral problems, and dysmorphic features. The region includes the gene MBD5 , or Methyl-CpG-binding domain 5. Loss of this gene is shown to cause the main symptoms of the 2q23.1 microdeletion; therefore, this disorder has also been termed MBD5 -Associated Neurodevelopmental Disorder (MAND).

Intellectual disability in the case of MAND includes speech and language impairment, seizures, walking abnormalities, autistic features, and stereotypies (repetitive movements or utterances). The behavioral problems can stem from anxiety, obsessive-compulsive disorder, and bipolar disorder. Dysmorphic features – which are notable abnormalities in the structure of the body, mainly the face – are not listed specifically inthis article, as they are variable among individuals.

Most cases of the 2q23.1 deletion are of de novo origin, meaning they occur spontaneously and are not inherited. This article presents three families with rare, inherited deletions of 2q23.1, involving MBD5 locus. In Family 1, the 10-year old daughter displayed seizures, intellectual delay, and developmental delay. Her mother, whom she inherited the deletion from, had severe childhood anxiety and mild psychosis. In Family 2, all three children had developmental delay and dysmorphic features. The mother, who also has the deletion, had no symptoms: she did not display learning difficulties, dysmorphism, or seizures. Family 3 had a child with learning disabilities, autism spectrum disorder, and seizures when younger. The father, who also has the deletion, had no history of developmental issues or seizures.

This article shows that the symptoms of the 2q23.1 deletion can vary significantly in individuals, from very severe in some, to little to nothing in others. As evident in the parents of Families 2 and 3, there are individuals who can have the deletion but show no symptoms. This shows that the variety of symptoms for this disorder is larger than previously thought. More research needs to be conducted to determine the reason behind the variety, and to explore the possibility of more inherited cases of the 2q23.1 deletions.