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.
- Spastic gait.
- Onset in the neonatal period, early infancy, or adulthood;
- Usually successfully responsive to antiepileptic drugs.
- Neuropsychiatric features.
- Attention deficit hyperactivity disorder (ADHD).
- Ophthalmologic abnormalities
- Abnormalities of refraction.
- Gastrointestinal abnormalities:
- (Neonatal) feeding difficulties.
- Gastroesophageal reflux.
- Ileal atresia.
A comprehensive spectrum of clinical characteristics observed in patients with autosomal dominant mental retardation-56 is available on the Graph and Chart page.
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.