Background: Spinal muscular atrophy (SMA) is a chronic, neuromuscular disease characterized by degeneration of
spinal cord motor neurons, resulting in progressive muscular atrophy and weakness. SMA1 is the most severe form
characterized by significant bulbar, respiratory, and motor dysfunction. SMA1 prevents children from speaking a clearly
understandable and fluent language, with their communication being mainly characterized by eye movements,
guttural sounds, and anarthria (type 1a); severe dysarthria (type 1b); and nasal voice and dyslalia (type 1c).
The aim of this study was to analyze for the first time cognitive functions, language comprehension, and speech in
natural history SMA1 children according to age and subtypes, to develop cognitive and language benchmarks that
provide outcomes for the clinical medication trials that are changing SMA1 course/trajectory.
Methods: This is a retrospective study including 22 children with SMA1 (10 affected by subtype 1a-1b: AB and 12 by
1c: C) aged 3–11 years in clinical stable condition with a coded way to communicate “yes” and “no”. Data from the
following assessments have been retrieved from patient charts: one-dimensional Raven test (RCPM), to evaluate
cognitive development (IQ); ALS Severity Score (ALSSS) to evaluate speech disturbances; Brown Bellugy modified for
Italian standards (TCGB) to evaluate language comprehension; and Children’s Hospital of Philadelphia Infant Test of
Neuromuscular Disorders (CHOP-INTEND) to assess motor functioning.
Results: SMA 1AB and 1C children were similar in age, with the former characterized by lower CHOP-INTEND scores
compared to the latter. All 22 children had collaborated to RCPM and their median IQ was 120 with no difference (p =
0.945) between AB and C. Global median score of the speech domain of the ALSSS was 5; however, it was 2 in AB
children, being significantly lower than C (6.5, p < 0.001).
TCGB test had been completed by 13 children, with morphosyntactic comprehension being in the normal range (50).
Although ALSSS did not correlate with both IQ and TCGB, it had a strong (p < 0.001) correlation with CHOP-INTEND described by an exponential rise to maximum.
Conclusions: Although speech and motor function were severely compromised, children with SMA1 showed general
intelligence and language comprehension in the normal range. Speech impairment was strictly related to global motor
impairment