Clinical Characteristics

Most individuals with Intellectual Developmental Disorder caused by mutations in SMARCB1 have features consistent with Coffin-Siris Syndrome (CSS).

All reported individuals have moderate to severe developmental delay/intellectual disability affecting language and motor development.

Most individuals have craniofacial and limb dysmorphisms consistent with a clinical diagnosis of CSS. These include sparse scalp hair, body hirsutism, coarse facial features with thick eyebrows, long eyelashes, flat nasal bridge, broad nose, and a wide mouth with a thick and everted lower lip vermillion. Typical limb anomalies include absence or hypoplasia of the 5th fingernails or toenails and hypoplasia of the 5th finger and toe; other digits may also be involved; prominence of the interphalangeal joints is also common.

Childhood hypotonia is common. Seizures are frequent complications. Microcephaly is seen in the majority but not all. Brain abnormalities are identified in over half individuals, most commonly hypoplasia or agenesis of the corpus callosum. Other less frequent brain malformations include ventriculomegaly, cerebellar hypoplasia and other posterior fossa malformations.

Feeding difficulties can be severe and persistent. Other gastrointestinal problems include gastroesophageal reflux and pyloric stenosis.

Affected individuals have poor growth, and short stature. Most develop scoliosis.

Congenital malformations
Congenital heart defects that have been reported in a small number of individuals include dextrocardia, pulmonic stenosis, ventricular septal defect, atrial septal defect. Diaphragmatic hernia has been reported in one patient. Genitourinary abnormalities reported in few individuals include cryptorchidism, hydronephrosis, horseshoe kidney, vesicoureteral reflux and vesical diverticulum.

Other problems
Other reported features include hearing loss, vision impairment, cleft palate, umbilical hernia and inguinal hernia.

Other IDD phenotypes
Four individuals with a recurrent missense mutation in the N-terminal domain of SMARCB1 (exon 2) have been reported to have intellectual disability and hydrocephalus due to choroid plexus hyperplasia. These individuals had severe intellectual disability, childhood hypotonia, hydrocephalus, and obstructive sleep apnea. Other features present not in all included kidney anomalies, congenital heart defects, genital anomalies, eye abnormalities and visual impairment, hearing loss, joint hypermobility, contractures and a history of anaemia.

SMARCB1 Intellectual Developmental Disorders are not known to be tumour predisposition conditions. However, one individual with Coffin Siris Syndrome with a mutation in exon 9 has been reported with multiple schwannomas of the spine, cranial nerves and soft tissues. Given the small number of patients reported, most at young ages, at this time it is not possible to determine whether the lifelong cancer risk is greater than that of the general population.