MED13L syndrome

MED13L syndrome is a rare developmental disorder characterized by intellectual disability, motor delays, distinctive facial features, and potential congenital heart defects.

Overview

MED13L syndrome is a developmental disorder characterized by developmental delay, intellectual disability, and minor differences in facial features. Some affected individuals also experience recurrent seizures (epilepsy) or heart abnormalities present from birth (congenital heart defects).

Symptoms

The clinical features of MED13L syndrome vary but typically include:

• Intellectual and Motor Delays: Intellectual disability and developmental delay are usually moderate to severe. Early symptoms include weak muscle tone (hypotonia) and delayed motor skills, such as sitting, standing, and walking. Some individuals experience ongoing difficulty with coordination and balance (ataxia) after learning to walk.
• Speech and Social Challenges: Speech is delayed, and most affected individuals develop only a few words or never learn to talk. Some may exhibit characteristics of autism spectrum disorder, including repetitive actions and social interaction difficulties.
• Distinctive Facial Features: Most individuals have unusual facial features, including outside corners of the eyes that point upward, an open mouth, a pronounced double curve of the upper lip, and a deep space between the nose and upper lip.
• Congenital Heart Defects: Various heart abnormalities can occur, including transposition of the great arteries (abnormal positioning of the aorta and pulmonary artery), a hole between the lower chambers of the heart (ventricular septal defect), a hole between the upper chambers of the heart (patent foramen ovale), or a complex combination of defects known as tetralogy of Fallot.

Frequency

MED13L syndrome is a rare disorder, occurring in an estimated 1.6 per 100,000 newborns. More than 65 affected individuals have been described in the scientific literature.

Causes

The condition is caused by mutations in the MED13L gene. This gene provides instructions for making a protein that regulates gene activity and plays an essential role in development both before and after birth. Mutations in this gene alter the function or reduce the amount of the MED13L protein, impairing normal control of gene activity. It is not yet clear how these changes lead to the specific developmental and physical features of the syndrome.

Associated Genes

• MED13L

Inheritance

MED13L syndrome is inherited in an autosomal dominant pattern, meaning one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from new (de novo) mutations that occur during the formation of reproductive cells or in early embryonic development, occurring in people with no family history of the condition.

Very rarely, the condition is inherited from a parent with mosaicism. In these cases, the parent has the mutation in only a small number of cells, including reproductive cells, and does not show any signs or symptoms of the syndrome.

Other Names for This Condition

• Asadollahi-Rauch syndrome
• ASRAS
• Cardiac anomalies-developmental delay-facial dysmorphism syndrome
• Developmental delay-facial dysmorphism syndrome due to MED13L deficiency
• Intellectual disability and distinctive facial features with or without cardiac defects
• MED13L haploinsufficiency syndrome
• MED13L-related intellectual disability
• MRFACD