Learning Difficulties in School-Aged Children: Uncommon Etiologies

Learning difficulties (LD) are one of the most common reasons for neurodevelopmental appointment in school-aged children. It is estimated that three million children worldwide, between the ages of six and 11, experience school or learning difficulties [1-3].

The definition of LD is not consensual. The term is used with different meanings, from mild difficulties to school failure. However, LD should be considered as a manifestation of a problem or a disease that may have several underlying etiologies. Currently, the Diagnostic and Statistical Manual of Mental Disorders - fifth edition (DSM-5-TR) does not include the term LD, considering only the specific learning disorder (SLD), which has individualized and specific criteria [4]. 

LD etiology is multifactorial and can be divided into intrinsic causes, namely neurodevelopmental disorders; and extrinsic causes, related to socio-familial environmental conditions or inadequate teaching methodology [2]. SLD, language disorders, attention deficit hyperactivity disorder (ADHD) and intellectual developmental disorder (IDD)/borderline cognition are some of the diagnoses most frequently associated with poor school performance [5]. However, neurological diseases or sensorial deficits may also explain LD [6-9]. 

LD can also be an expression of a wide spectrum of clinical conditions that can coexist. A detailed medical history and physical examination are critical for the initial diagnosis and etiological investigation and exclusion of serious or less common etiologies or diseases that require specific treatment [3].

We describe three cases of children referred to neurodevelopmental appointment for LD and whose diagnoses were: developmental coordination disorder (DCD), epilepsy and ADHD and neuromuscular disease. We intend to highlight the wide range of differential diagnosis and to reinforce the importance of an accurate medical history and a multidisciplinary evaluation.

Case one

An eight-year-old boy was referred to neurodevelopmental appointment for suspected dysgraphia. At first visit, he was in fourth grade, with good school performance, but the family was concerned about his fine motor skills (e.g. pre-writing skills, cutting with scissors) since kindergarten. Difficulties were also described in gross motor skills, namely activities that required constant changes in his body position (some sports) and in daily tasks (e.g. dressing, eating, and tying shoelaces). Reading abilities were regular, but his handwriting was irregular, difficult to read, and with frequent misspellings. There were no complaints about behavior, namely inattention, and there were no suspected sensorial deficits. Growth was regular and all psychomotor milestones were acquired at typical ages, including major motor and language skills. Family history was unremarkable. Physical examination revealed a child with an unstable gait without preferential side, difficulty walking in a straight line, mild intention tremor and mild bilateral dysmetria and dysdiadochokinesia. 

These clinical manifestations triggered a multidisciplinary evaluation and etiological investigation. Cognitive assessment with the Wechsler Intelligence Scale for Children (WISC-III) [10], showed cognitive performance within the expected average for his age. He underwent a pedagogical evaluation that reinforced the hypothesis of a diagnosis of dysgraphia. He demonstrated good attentional skills during the cognitive and pedagogical evaluation. Occupational therapy evaluation identified dysregulation in sensory processing and difficulty in bilateral motor coordination with low functional performance. Strategies were provided to improve motor performance, with a positive clinical impact. He performed brain magnetic resonance imaging (brain MRI) and analytical evaluation (blood count, renal function, transaminases, creatine phosphokinase [CPK], lactate dehydrogenase [LDH], venous blood gases, thyroid hormones, copper metabolism) - all normal. Visual function examination was normal. The diagnosis of DCD was established, and the child started Special Education Support (SES) measures at school. He maintains follow-up in neurodevelopmental appointment and occupational therapy. He is currently in fifth grade, and despite higher demands of the school curriculum, he has been improving with the adequate support measures. 

Case Two 

An eight-year-old girl was referred to neurodevelopmental appointment for LD. Initial concerns were reported in preschool, with difficulties in comprehension, memory and increased time to fulfill tasks. The difficulties gradually increased, particularly in reading, writing and logical reasoning. Additionally, she showed frequent inattention, lack of autonomy and difficulty in organizing tasks. After tonsillectomy and myringotomy at six years old she underwent audiological evaluation, which was unremarkable. The cognitive assessment (WISC-III) performed, at the age of seven, showed a cognitive level within the mean expected for her age but with difficulties in sustaining attention, short-term memorization, planning, and visuospatial coordination. She fulfilled DSM-5-TR ADHD diagnostic criteria (predominantly inattentive presentation) and started pedagogical support since second grade. When she was at third grade, difficulties in mathematics increased. Sleep was described as very agitated, requiring a bed rail to avoid falls. There were no sudden stops of activity, loss of consciousness or nocturnal enuresis. Behavior was unremarkable. Physical examination was normal. She had two maternal second-degree cousins with epilepsy and IDD. The electroencephalogram (EEG) revealed generalized paroxysmal activity in photic stimulation (Figure 1) and right central spikes in sleep (Figure 2). Brain MRI was normal. She started levetiracetam therapy with improvement of sleep pattern. Despite epilepsy control, she maintained LD. Cognitive reassessment was done. The global intelligence quotient was one standard deviation above the mean for her age (borderline cognition), with strong difficulties in memory, processing speed and sustained attention abilities.

Currently, epilepsy is controlled with antiseizure medication. She maintains follow-up in both neurodevelopmental and neuropediatric appointments and benefits from SES. Improved attention and planning performance was achieved after introduction of a psychostimulant drug (methylphenidate), with good tolerance and no adverse effects. 

Figure 1: Interictal electroencephalogram with generalized paroxysmal activity (spike-and-wave at 3-4 Hz) in photic stimulation at 15 Hz with eyes closed.

 Figure 2: Interictal electroencephalogram in sleep with right central spikes (phase opposition in C4).

Case three 

An eight-year-old girl was referred to neurodevelopmental appointment for LD and concerns regarding global motricity. She acquired main developmental milestones at expected ages, including motor landmarks. However, at the age of four, it was reported imbalance and frequent falls, difficulty in running and climbing stairs. Additionally, she presented greater fatigue in daily activities compared to her twin sister. There were no complaints of palpebral ptosis or daily variation of the symptoms. Perinatal history was unremarkable. Family denied repeated respiratory infection, constipation or feeding difficulties. Growth was regular. Parents were non-consanguineous and there was no family history of LD or neurological diseases. A school report highlighted difficulties in all subjects, slow and unprecise syllabic reading, difficulties in mental calculus, comprehension and problem solving, temporospatial orientation, and working memory. Behavior and sleep were normal. Neurological examination showed bilateral varus gait, decrease in muscle strength in flexion of the neck and extension of the thigh (grade 3/5), a positive Gowers maneuver, without evidence of winged scapula or spine deviations. Myotatic reflexes were diminished, and speech and cranial nerves evaluation were normal. 

She was also observed in neuropediatric appointment and began investigation for neuromuscular disease. CPK serum level was 1266 U/L (reference value:

LD is a common reason for referral to neurodevelopmental appointments. There is great clinical heterogeneity depending on the etiology and comorbidities associated, which includes common problems such as SLD, ADHD and IDD, but also some rare diseases such as neuromuscular diseases.

Regarding case one, DCD is a poorly understood problem, but its prevalence is 5-6% between the ages of five and eleven [4,11]. According to DSM-5-TR, the acquisition and execution of coordinated motor skills is substantially below the expectations for the chronological age, learning opportunities and abilities of the individual [4]. This impairment of motor skills significantly interferes with the performance of daily tasks [4,11,12]. There may be a delay in motor milestones (e.g. sitting, walking), although many children reach them at normal ages [4]. Younger children may have difficulty walking up and down stairs, pedaling, doing up buttons and zippers. Older children and adults present lower speeds or inaccuracy in motor activities such as ball games, handwriting and driving. DCD may also affect cognitive and social development, since motor control is essential for interacting with the environment [13]. The diagnosis of DCD, according to DSM-5-TR, is based on developmental and medical history, physical examination, school or workplace report, and individual assessment using psychometrically sound and culturally appropriate standardized tests. The symptoms begin during early developmental period, but, usually, diagnosis is not made before the age of five due to a significant variation in the acquisition of motor skills in early childhood, or because the symptoms only become clear once the academic complexity increases, and school performance is affected. The difficulties are also not better explained by visual impairment or neurological condition affecting movement (e.g., cerebral palsy, muscular dystrophy, degenerative disorder), whereby visual examination and neurological examination must be included [4]. In selected cases, depending on clinical findings, additional evaluation can be considered. The case presented demonstrates how DCD can have an impact at academic level and how the symptomatology can be undervalued until it interferes in school performance. These children need school support measures, such as adaptations in evaluation process (e.g. having extra time for the test, test/exam sheets in accessible formats) [14], so that they feel that their effort is rewarded, avoiding feelings of low self-esteem, insecurity, or opposition. DCD is usually associated with other comorbidities, such as problems of inattention (ADHD up to 50% of the cases) and SLD, mainly in reading and writing, as in the case presented (dysgraphia) [4,15]. 

As a potentially treatable condition, with high impact in neurodevelopment and learning, epilepsy diagnosis should be kept in mind. The pediatrician should recognize the multiple forms of presentation which may suggest the diagnosis. Therefore, and as demonstrated in case two, it is essential to characterize sleep, namely the existence of falls, sudden "stretching", enuresis, non-repairing sleep or morning irritability, as well as episodes of sudden stop of activity or syncope. The EEG, with sleep recording, is a fundamental element in the diagnosis. There are several recognized clinical syndromes and the impact on neurodevelopment is related to the type of epilepsy, age of onset, frequency of seizures, treatment and symptomatic control [16]. Although most children and adolescents with epilepsy have average intellectual functioning, the impact on learning may be significant [17]. As case two revealed, despite epilepsy control, they can have ADHD as comorbidity demonstrating higher levels of inattention, slow performance and significant interference in working memory and executive functions. These deficits have a high impact on academic performance, especially in problem solving, planning and mental flexibility. In addition to educational and behavioral measures, depending on epilepsy etiology and control, stimulant therapy can be considered with close monitoring [18].

Neuromuscular diseases have multiple comorbidities, including neurodevelopmental disorders. It is reported that 44% of the cases of Duchenne muscular dystrophy have learning disabilities and 17% intellectual disability [17]. Severity relates to the underlying etiology. First red flags may occur in the prenatal period (decreased fetal movements, polyhydramnios, arthrogryposis) or in the first years of life (delayed acquisition of gross motor milestones, abnormal growth, respiratory infections). However, the manifestations may be milder and occur later, particularly with complaints of muscle weakness, fatigability, and palpebral ptosis. In case three, there were early complaints that could lead to the suspicion of a neuromuscular disease, but only the LD motivated the referral to neurodevelopmental appointment. The abnormal findings in physical examination, associated with complaints of fatigue and reduced motor agility, suggested this diagnosis. Neurological exam may disclose some specific features regarding underlying etiology and pathophysiology of the disease (muscle and/or nerve). They may include decreased muscle strength, diminished reflexes, muscle hypertrophy (e.g. lower leg muscles pseudohypertrophy) or hypotrophy (e.g. “winged scapula”), tendon retractions, abnormal gait (e.g. toe walking) and hyperlordosis. The etiological investigation begins with less specific tests (serum CPK, LDH and transaminases), proceeding to more specific examinations like electromyography, MRI, muscular biopsy, and genetic study. In our case, the genetic study found a rare disease, Bethlem myopathy, with an estimated prevalence of less than 1:1.000.000 according to ORPHANET [19]. It is an autosomal dominant disease, but there are cases described in heterozygosity and with recessive transmission [20]. There is usually a slow progression, with preserved ambulation in adult life [21]. As in the previous case, the multidisciplinary approach along with neuropediatric, psychology and other technical support were essential.

We reported three cases of children referred to neurodevelopmental appointment for LD who raised several diagnostic and therapeutic challenges. Physicians working with children should remember that LD are a first sign of a wide spectrum of clinical conditions that can coexist. A detailed medical history and physical examination are critical for the initial etiologic investigation and subsequent diagnosis. SES and multidisciplinary care are fundamental to improve outcomes of children with LD.

There are no acknowledgments for this submission.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

The authors have no conflicts of interest to declare.

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