Developmental milestones of 130 male children with Duchenne’s muscular dystrophy (DMD) and their 59 unaffected siblings were determined by retrospective parental reports and compared by researchers at the City University and Columbia University, New York, NY; and Scottish Rite Children’s Medical Center, Atlanta, GA. Participants were recruited through the Muscular Dystrophy Association clinics at these institutions. Children with DMD were 4-14 years of age (mean, 9 years), and sibling controls 3-16 years (mean, 9.85 years). Parents completed a developmental milestone questionnaire and Child Behavior Checklist. Neuropsychological testing included measures of language, memory, and visuospatial skills (Peabody Picture Vocabulary Test, and the Raven’s Colored Progressive Matrices). Children with DMD were rated late more often than their unaffected siblings in motor milestones such as sitting (38% vs 0%), crawling (60% vs 6%), standing (56% vs 0%), and walking (70% vs 2%)(P<.001). They were also late in speaking their first word (42% vs 4%) and in using full sentences (49% vs 4%)(P<.001), and in reading (94% vs 6%)(P<.001). Development of other milestones (smiling, bowel or bladder control) was not delayed. DMD children late in constructing complete sentences performed poorly on measures of single-word vocabulary (P<.001) and visuospatial reasoning (P=.002), compared to DMD children whose language development was on-time. Behavioral difficulties were not significantly different in the two groups of DMD children. DMD children rated late in walking performed more poorly on a measure of visuospatial reasoning (P<.02), but were not different in acquiring single-word vocabulary nor in frequency of behavioral issues when compared with DMD early walkers. 
COMMENT. In addition to delays in motor milestones, children with DMD are late in speaking single words and sentences. The late talkers also develop cognitive deficits involving vocabulary. Both late talkers and late walkers function poorly on tests of visuospatial reasoning. Age at taking the first step is generally considered the most reliable milestone based on parents’ recollection, while sitting and uttering the first word are less well timed. In the present study, by focusing on broad categories (“on-time” and “late”) and by using siblings as controls, the authors have attempted to minimize the limitations of a retrospective study.
Although DMD is primarily a disease of muscle, unexplained language and developmental delay may precede significant signs of muscle weakness, and point to a coincident CNS disorder. Deficiency of brain synaptic dystrophin was demonstrated in an 8-year-old child with DMD examined at autopsy . Several studies have demonstrated the association of cognitive deficits, especially specific verbal impairments in children and adolescents with DMD. The present report shows that delayed language milestones may be the earliest sign of DMD, and an important observation in the clinical diagnosis. The need for further study of brain dysfunction in children with DMD is indicated.