Strumpellin is highly expressed in skeletal muscle cells and mutations in it are also associated with spastic paraplegia. Strumpellin is involved in endosomal transport and cell death processes. The mutation occurs at a splice site  and causes a substantial decrease in the amount of strumpellin produced by the cell. The phenotype is similar to 6pter-p24 deletion syndrome and 6p25 deletion syndrome but has a different etiology. Screening for the condition prenatally may be done with ultrasound. First-trimester ultrasounds can detected nuchal abnormalities
Second-trimester ultrasounds can pick up characteristic major structural abnormalities.Prenatal diagnosis is possible through genetic testing. Chorionic villus sampling or chorionic villus biopsy (CVS) in the first-trimester. Amniocentesis in the second-trimester.Because 3C syndrome is an autosomal recessive disorder, parents with one child with the disorder have a 25% chance of having another child with the disorder. Diagnosis
Differential diagnosis
There is an overlap in symptoms between 3C syndrome and Joubert syndrome. Joubert syndrome often manifests with similar cerebellar hypoplasia and its sequelae, including hyperpnea, ataxia, changes in eye movement, and cleft lip and palate. Occasionally, Joubert syndrome will include heart malformations. Brachmann–de Lange syndrome must also be differentiated from 3C syndrome. It presents with similar craniofacial and heart abnormalities and can include Dandy–Walker phenotype, making it difficult to distinguish. Dandy-Walker malformation is also occasionally seen in Ellis–Van Creveld syndrome, which is characterized by heart defects and malformed alveolar ridge. Many disorders include the Dandy–Walker phenotype and thus it is not pathognomonic for 3C syndrome.CHARGE syndrome can also be misdiagnosed.
This is because both CHARGE syndrome and 3C syndrome share symptoms of ocular colobomas, cardiac defects, growth retardation, and minor facial abnormalities.Coffin–Siris syndrome presents with fifth-finger deformities and congenital heart defects. It is distinguished from 3C syndrome by differences in facial dysmorphisms. Management
The outcome of this disease is dependent on the severity of the cardiac defects. Approximately 1 in 3 children with this diagnosis require shunting for the hydrocephaly that is often a consequence. Some children require extra assistance or therapy for delayed psychomotor and speech development, including hypotonia. Prognosis
Prognoses for 3C syndrome vary widely based on the specific constellation of symptoms seen in an individual. Typically, the gravity of the prognosis correlates with the severity of the cardiac abnormalities. For children with less severe cardiac abnormalities, the developmental prognosis depends on the cerebellar abnormalities that are present. Severe cerebellar hypoplasia is associated with growth and speech delays, as well as hypotonia and general growth deficiencies. Epidemiology
3C syndrome is very rare, occurring in less than 1 birth per million. Because of consanguinity due to a founder effect, it is much more common in a remote First Nations village in Manitoba, where 1 in 9 people carries the recessive gene. History
The syndrome was first reported in 1987 in two sisters who had similar craniofacial abnormalities, Dandy–Walker phenotype, and congenital heart abnormalities. Neither of the parents was affected, indicating that the disorder was transmitted in an autosomal recessive pattern.