Families

Clinical features
Individuals with SHMT2 brain and heart developmental syndrome can have a characteristic and identifiable clinical phenotype that is consisted with intellectual disability, motor dysfunction in the form of spastic paraparesis (stiffness of the legs), ataxia (loss of muscle coordination), and/or peripheral neuropathy. Patients present also congenital microcephaly and dysmorphic features (long palpebral fissures, eversion of lateral third of lower eyelids, arched eyebrows, long eyelashes, thin upper lip, long philtrum, short fifth finger, fleshy pads at the tips of the fingers, mild 2-3 toe syndactyly and low-set thumbs).
Most of the reported cases had hypertrophic cardiomyopathy or atrial-septal defects, which tend to progress over time.

Prevalence
SHMT2 brain and heart developmental syndrome is extremely rare and to date only 5 patients have been reported in the literature.

Inheritance
SHMT2 brain and heart developmental syndrome is a genetic disorder due to mutations in SHMT2. The disease is inherited in an autosomal recessive manner: this means that both copies of the SHMT2 gene must be mutated in an individual to be affected, whereas heterozygotes (with only one mutated copy) are asymptomatic carriers and thus do not manifest the condition but are at risk of transmitting it. Parents of a patient are usually carriers of the mutations and they have a 25% chance to have other children affected. Therefore, a genetic counselling and testing at risk family members are crucial for these families.