Data from three adult male patients with late-onset SMA are presented in this case series. Two of the three individuals were diagnosed with Type 3 SMA and had four SMN2 copies. The third individual was diagnosed with Type 4 SMA and had four SMN2 copies.

All three individuals were counseled on the potential impact of risdiplam on male fertility, and there was no intention to conceive with their partners. The male patients were taking risdiplam (5 mg once daily) during the window of conception; there was no concern that the patients missed any doses. Of these three pregnancies, two were full term and resulted in healthy babies, and one was voluntarily terminated.

Patient 1 is a 34-year-old man who started having difficulty with walking at 8 years of age (Table 1). After increasing difficulty with school sports, the patient presented to a pediatrician and was diagnosed at 15 years of age with SMA via genetic testing, with a clinical course consistent with Type 3 SMA.

This patient was initially prepared to receive nusinersen (SPINRAZA®) treatment but began risdiplam treatment instead after approval in November 2021, when he was 32 years old. Over 30 months of risdiplam treatment, his motor function as measured by Hammersmith Functional Motor Scale–Expanded was stable; respiratory and bulbar functions were both normal (Supplementary Table S1). There was an improvement in fatigue as measured using the Fatigue Severity Scale before and after 30 months of treatment (score 3.7 versus 2.2, respectively). There were no adverse events or hospitalizations that were related to risdiplam treatment, and the patient remains on risdiplam to date. The patient and his partner had no formal fertility testing completed; the partner had lipedema but otherwise was healthy and taking oral contraceptives. While on treatment with risdiplam, he and his partner conceived in January 2023, which resulted in the birth of a healthy, male infant in October 2023. The baby was healthy and had a normal APGAR score of 10 at 1, 5, and 10 min. At birth, the baby was in the 7th percentile in weight and 16th percentile in length. At 3.5 months of age, the baby measured at the 11th percentile in weight and 70th percentile in length (Supplementary Table S2).

The main concern for the patient was how SMA would impact everyday life, particularly as a result of fatigue. He was afraid of losing his ability to walk, of no longer being able to cope with everyday life and potentially having professional limitations. For a long time, the patient was aware that he might never be able to have children of his own. Treatment with risdiplam has brought about fundamental changes in his life: he has remained mobile, no longer suffers from fatigue, is better able to pursue his career, and, above all, suddenly has the opportunity to start a family with his partner.

Patient 2 is a 28-year-old man who presented with symptoms of SMA (abnormal gait, frequent falls) at 2 years of age (Table 1). At 13 years of age, he was diagnosed with SMA via genetic testing with a clinical course consistent with Type 3 SMA. In January 2021, he chose risdiplam treatment owing to a desire to slow disease progression and because of the route of administration (lumbar punctures) required for nusinersen treatment. Motor function before risdiplam treatment was not measured, but after patient 2 received risdiplam for 2 years, his modified Hammersmith Functional Motor Scale and Revised Upper Limb Module scores were 27 and 33, respectively. Bulbar function was normal before and after risdiplam. The patient was hospitalized with abdominal pain and anorexia that were related to risdiplam; the patient discontinued risdiplam in February 2023 because of gastrointestinal side effects. Two weeks after discontinuing risdiplam these side effects resolved.

The patient and his partner had no formal fertility testing completed, but the partner had polycystic ovary syndrome (PCOS). As a result of the misperception of infertility due to the PCOS diagnosis, patient 2 and his partner did not use contraception, and patient 2 remained on risdiplam during the window of conception. Patient 2 and his partner conceived in February 2022, which resulted in the birth of a full term, healthy female infant in November 2022. The baby is a healthy 18-month-old who at birth had an APGAR score of 10.

Patient 3 is a 21-year-old man who was diagnosed with SMA at 16 years of age via genetic testing, with a clinical course consistent with Type 4 SMA (Table 1). He was first treated with nusinersen from July 2019 to September 2020 but discontinued treatment because of nausea and back pain. He began risdiplam in January 2021 and remains on treatment to date.

When compared with baseline motor and respiratory function measures, there was an improvement after 21 months of risdiplam treatment in Hammersmith Functional Motor Scale–Expanded score (42/66 vs 56/66, respectively) and peak cough flow (730 vs 861 L/min, respectively). Bulbar function was normal before and after initiating risdiplam. The patient presented with chronic, but minimally bothersome diarrhea since starting risdiplam.

The patient and his partner had no formal fertility testing completed. The partner is healthy with no fertility concern. While on treatment with risdiplam, patient 3 and his partner were using condoms and had an accidental conception in September 2023. The pregnancy was voluntarily terminated through an elective abortion.

Patient 3 graduated from high school and completed courses in local community college but struggles with workplace opportunities because of persistent weakness. The patient expressed stability since starting treatment with risdiplam. He is highly motivated to understand the impact that risdiplam had on fertility given his desire to have children in the future.