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Mental Retardation, AD 57

OMIM ID:

autosomal dominant

Mental Retardation, AD 57

Alternate Names

MRD57

Defective Genes

TLK2

Clinical Characteristics

Ocular Features

Ptosis, strabismus, epicanthal folds, and upslanting lid fissures are often present but there is considerable variation among individuals.  Blepharophimosis, telecanthus, and various refractive errors have also been reported.

Systemic Features

There is great variability in the clinical signs among patients.  Most have developmental delays and intellectual disabilities combined with behavioral challenges such as anxiety, obsessive-compulsive disorders and features of autism spectrum disorders.  

Infants and young children may have feeding difficulties but may later develop constipation or diarrhea.  

Skeletal anomalies such as short stature, high palate, craniosynostosis, scoliosis, pes planus, hand contractures, and joint hypermobility have been reported.  The voice may be hoarse.

Genetics

Inheritance

Heterozygous mutations in the TLK2 gene (17q23) are responsible for this condition.

Pedigree

Autosomal dominant

Autosomal dominant disorders require only one mutation for the disease to be expressed.  Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease.  It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).

Image
Sample pedigree of autosomal dominant inheritance

Autosomal dominant inheritance leads to a vertical pattern of transmission

Treatment & Management

No treatment has been reported.

Selected Resources

Web Resources

Publications

Displaying 1 - 2 of 2

De Novo and Inherited Loss-of-Function Variants in TLK2: Clinical and Genotype-Phenotype Evaluation of a Distinct Neurodevelopmental Disorder

PubMedID: 29861108

Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability

PubMedID: 27479843