Most individuals with Intellectual Developmental Disorder caused by mutations in SMARCB1 have been diagnosed clinically with Coffin-Siris Syndrome (CSS).
All individuals we know of to date have moderate to severe delay in their developmental milestones and learning disability.
Most individuals share characteristic physical features of CSS. These include sparse hair of the scalp, increased body hair, thick eyebrows, long eyelashes, large mouth and thick lips. They can also have short fingers, namely the 5th finger of the hands and 5th toe, which can be short and/or have a small or absent nail. They can also have enlarged joints of the fingers.
Neurologic
Babies and children have low muscle tone (hypotonia, or “floppy baby”). Most, though not all, develop fits (seizures, epilepsy). Also, most have a smaller head than expected for age. Some patients have changes in the brain that are detected by MRI, namely smaller or absent corpus callosum (the bridge between the two sides of the brain). Other less frequent brain malformations include enlargement of the fluid spaces in the brain and malformations of the cerebellum (a structure at the bottom back of the brain).
Gastrointestinal
Feeding difficulties can be severe and long lasting. Other gastrointestinal problems include gastroesophageal reflux, when stomach acid comes back up, and pyloric stenosis (a tightening of the passage from the stomach to the small bowel).
Musculoskeletal
Affected individuals have problems with growth throughout their lives, and tend to be shorter than expected compared to the rest of the family. Most develop scoliosis, a sideways curve of the spine.
Birth defects
Some individuals are born with different types of heart defects. These have included, for example, holes between the different chambers of the heart (ventricular or atrial septal defects), abnormal positioning of the heart to the right side (dextrocardia). It is important to note that these are defects present at birth; i.e. if a baby is born with a normal heart, they will not develop these later on. Other individuals have been born with kidney problems (such as malformed kidneys or reflux of urine from the urine back into to the kidneys). Boys may have undescended testicles.
Other problems
Other reported problems have included hearing loss, poor vision, cleft palate (a gap in the roof of the mouth) and hernias of the groin or umbilicus.
Other developmental phenotypes
Four individuals that all shared the same mutation in a specific region of the SMARCB1 gene were reported to have severe learning disability and build-up of fluid in the brain (hydrocephalus), without the characteristic physical features of Coffin-Siris Syndrome. These children had problems with breathing during sleep, and some also had heart and kidney problems or poor vision and hearing loss.
SMARCB1 Coffin Siris Syndrome and learning disability are not known to be cancer predisposing conditions. A different type of change in SMARCB1 (loss of function mutations) cause a distinct group of disorders, where specific types of cancer can run in the family and learning disability is not a feature. The type of mutation that causes learning disability is different, and only one patient with learning disability and a mutation in SMARCB1 has been reported to have cancer. However, we do not know enough about the condition to be able to determine whether patients may have a higher risk than others to have certain types of cancer.