The known severe new signs of SAMD9L deficiency are myelodysplastic syndrome (MDS) and acute myeloid leukemia. It is still unknown how high the risk of developing these manifestations is. Moreover, it is also possible for cytopenia to develop as part of SAMD9L deficiency, with anemia – a lack of red blood cells – being the most common form. The severity of the cytopenia can range from mild to very severe. The earliest onset described for any disease of the blood-formation system is 3 months of age, although there is a high degree of variability with regard to the manifestation age as well.
Other forms of manifestation are neurological diseases. An anomaly of the nervous system has so far been diagnosed in all patients with a SAMD9L mutation. For example, cerebellar ataxia (a movement coordination disorder caused by damage in the cerebellum) has been identified. Signs of such ataxia include gait and balance difficulties, rhythmic eye twitching (nystagmus), exaggerated reflexes, and enunciation difficulties. Impaired gait and other neurological anomalies generally exhibit a slow progression. The age of onset has a very wide range – from infancy to 62 years. It is also possible for neurological symptoms to be absent.