A Rare Cause of Intellectual Disability

Abstract

A seven-year-old female was followed in a developmental clinic from the age of nine months due to delayed psychomotor development. The first physical examination showed a newborn with irritability and a large anterior fontanelle. A transfontanellar ultrasound was performed, revealing mild enlargement of the lateral and third ventricles. Head circumference remained below the third percentile until the age of five months, then rose to the third percentile. Developmental milestones were globally delayed, with expressive language being more severely affected and axial hypotonia with appendicular hypertonia on neurological examination. Subsequent medical observation revealed deep-set eyes, mildly up-slanted palpebral fissures, a high nasal bridge with a broad nasal tip, a thin upper lip, widely spaced teeth, retrognathia, and a slight pectus excavatum. Genetic investigation revealed the diagnosis, with whole-exome sequencing consistent with the genetic diagnosis of autosomal dominant mental retardation type 7 (MRD7). All patients diagnosed with MRD7 have a development delay detected at a young age and, typically, a mild to severe intellectual disability later in life. All individuals present language impairment, especially in verbal expression. Motor development is typically affected by gait disturbances and generalized hypertonia, which are noted early in life. Microcephaly is a prominent feature of this syndrome, present in over 90% of the cases. The most common findings in MRD7 (microcephaly and intellectual disability) have a broad differential diagnosis. Some disorders have multiple findings in common with MRD7, such as Angelman syndrome (AS), MECP2 disorders, or Mowat-Wilson syndrome (MWS). MRD7 is a rare genetic syndrome characterized by developmental delay/intellectual disability, microcephaly, autism spectrum disorder, behavior problems, typical facial features, and seizures. Early intervention is more likely to be effective and potentially change a child's developmental path. Small gains early in life could represent a significant difference in the children's future autonomy.