Clinical Presentation of SMA
SMA has historically been categorized into subtypes based on age that symptoms begin and highest motor milestone achieved. This classification continues to apply to adults, teens, and some children in SMA. The most common three types in children present as follows:
Symptom onset <6 months
Historically Type 1 (SEVERE/MOST COMMON FORM)
- Progressive hypotonia
- Typical supine position is bent elbows and frog legs
- Difficulty lifting extremities against gravity
- Rapid paradoxical breathing or belly breathing
- Bell-shaped chest
- Poor head control / head lag
- Bulbar weakness / dysphagia
- Developmental regression
- Never sits
Symptom onset 6 to 18 months
Historically Type 2
- Progressive hypotonia
- Difficulty lifting extremities against gravity
- Possible paradoxical breathing or belly breathing
- Possible bell-shaped chest
- Tongue fasciculations
- Absent deep tendon reflexes
- Developmental regression
- Delayed sitting and never walks unaided
Symptom onset 1.5 to 10 years
Historically Type 3
- Progressive hypotonia
- Muscle tremor
- Fatigue with exertion and frequent falls
- Gower’s sign, Trendelenburg gait, hyperlordosis, and foot overpronation
- Developmental regression
- Delayed walking
Following the approval of the first disease modifying treatments for SMA in 2016 (an SMN enhancing therapiesy) and the implementation of newborn screening for SMA in 2018, the historical classification of SMA does not adequately describe the new generation of infants and children with SMA treated early in life. In addition, more infants are being diagnosed and receive treatment prior to the onset of symptoms. With treatment, individuals are gaining more physical milestones and abilities than natural history would predict.
The SMA community of healthcare providers, people with SMA, and their families are having many conversations about how to best describe SMA disease in the era of disease modifying SMA treatment. Characteristics that have risen to the top and that are generally used together include:
SMN2 copy number (SMN2 is an important disease modifying gene. Click here for more information).
- Current motor function
- Age atsymptom onset
- Impact of symptoms or the severity of symptoms
Click here for a Reference Guide to Clinical Presentation
Although SMA newborn screening has been implemented in all 50 states, providers should remain watchful, as approximately 3% to 5% of individuals with SMA will not be identified by newborn screening due to SMN1 point mutations. Promptly evaluate for SMA upon suspicion in clinic. Additional genetic testing, SMN1 gene sequencing, may be required to evaluate for SMA. Rapid response can save and dramatically improve a child’s life.
SMArt Moves Professionals’ Proof Points
Historically, healthcare professionals have been slow to refer a child for concerns about motor delays. In part, SMA is a rare disease and an SMA diagnosis was once perceived as dismal, prior to the availability of the first FDA-approved treatment for SMA in 2016. There are now multiple FDA-approved treatments for SMA, and additional treatments in development or in clinical trials. With the availability of these life-altering SMA treatments, the timing of administration is crucial.
- Early treatment, within the first few months after exhibiting SMA symptoms, will show significant improvements. SMA treatment started after that crucial early window can still result in benefit, but their health outcomes and improvements may not be as great compared to children treated at the earliest onset of the disease.
- Most children are not being diagnosed as early as possible, even when presenting tell-tale symptoms.
- Most parents instinctually know something is wrong but are not exactly sure if these developmental delays are serious, or they may be in denial. If a healthcare professional initially dismisses concerns, parents are generally not prepared to prompt further conversations to drive a thorough evaluation.
- Doctors often suggest a “wait-and-see” approach in response to a child’s motor developmental delays and may not be attune to the nuances of diagnosing SMA. They may not know the urgency required to maximize the effectiveness of available SMA treatment.
We hope this information will help you make informed decisions about diagnosing SMA and change the outcome for so many young children and their families.
Additional Facts & Resources
References:
Finkel RS, Mercuri E, Darras BT, et al. Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy. N Engl J Med. 2017;377(18):1723–1732. doi:10.1056/NEJMoa1702752 https://www.nejm.org/doi/full/10.1056/NEJMoa1702752
Mendell JR, Al-Zaidy S, Shell R, et al. Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy. N Engl J Med. 2017;377(18):1713–1722. doi:10.1056/NEJMoa1706198 https://www.nejm.org/doi/10.1056/NEJMoa1706198
Mercuri E, Darras BT, Chiriboga CA, et al. Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy. N Engl J Med. 2018;378(7):625–635. doi:10.1056/NEJMoa1710504 https://www.nejm.org/doi/full/10.1056/NEJMoa1710504
De Vivo DC, Bertini E, Swoboda KJ, et al. Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study. Neuromuscul Disord. 2019;29(11):842–856. doi:10.1016/j.nmd.2019.09.007 https://www.nmd-journal.com/article/S0960-8966(19)31127-7/fulltext
