Clinical Characteristics

Clinical Characteristics

Pathogenic variants in the CLTC gene cause autosomal dominant mental retardation-56 (MRD56; MIM#617854), a multisystem disorder.
All individuals with this disorder have these features:

  • Developmental delay (motor and/or speech delay).
  • Intellectual disability, ranging from mild to moderate.
  • Subtle facial dysmorphisms.
    • Long face.
    • High, narrow forehead.
    • Wide nasal bridge.
    • Wide-set and long palpebral fissures.
    • Large, protruding, and/or low-set ears.
    • Deep philtrum with prominent philtral ridges and an exaggerated groove in the midline.
    • Wide mouth with thick lower vermilion.
    • Large upper central incisors.
    • Mild facial asymmetry (rarely).

Other reported clinical features are:

  • Structural brain abnormalities.
    • Hypoplasia of the corpus callosum (a thin, small corpus callosum, but with all segments present).
    • Dilated Virchow–Robin spaces.
    • Asymmetric or dilated ventricles.
    • Frontal atrophy.
    • Pontocerebellar atrophy.
    • Abnormal myelination.
  • Microcephaly (associated with hypoplasia of the corpus callosum).
  • Neurologic problems.
    • Hypotonia.
    • Ataxia.
    • Spastic gait.
    • Epilepsy.
      • Onset in the neonatal period, early infancy, or adulthood;
      • Usually successfully responsive to antiepileptic drugs.
  •  Neuropsychiatric features.
    • Attention deficit hyperactivity disorder (ADHD).
    • Autism.
  • Ophthalmologic abnormalities
    • Strabismus.
    • Abnormalities of refraction.
  • Gastrointestinal abnormalities:
    • (Neonatal) feeding difficulties.
    • Gastroesophageal reflux.
    • Constipation.
    • Ileal atresia.
    • Achalasia.

A comprehensive spectrum of clinical characteristics observed in patients with autosomal dominant mental retardation-56 is available on the Graph and Chart page.

Variable expressivity
The severity of intellectual disability (ID) and the occurrence of additional clinical features is variable among individuals autosomal dominant mental retardation-56. Moderate/severe ID associated with the clinical triad microcephaly, hypoplasia of the corpus callosum, and epilepsy may occur in more severely affected individuals. Less severely affected individuals present with mild ID/learning disability (without epilepsy or brain abnormalities).

It is not possible to predict beforehand the degree of intellectual disability or which additional clinical manifestations an individual with a pathogenic variant in the CLTC gene will develop solely based in the genotype.