Developmental defects of the cranium and the brain may be clinically isolated or occur as part of complex syndromes associated with other neurodevelopmental challenges, brain defects and abnormal body growth . Research has shown that macrocephaly and microcephaly are still poorly defined and a uniform diagnostic approach is urgently needed. Definitive etiological diagnosis is crucial for predicting outcomes and for designing treatment administered to the affected patients [7–15]. This observation provided a motivation for the current study. Another reason was the fact that, to our knowledge, no studies have investigated the relationships between co-occurring abnormal cranium development and diseases or syndromes linked with neurodysfunction. Hence, the present study is the first one to offer scientific evidence related to this issue.
According to Pirozzi et al., neurodevelopmental impairments linked with abnormal growth of the brain, with or without cortical defects, significantly contribute to morbidity and mortality, and are associated with numerous consequences of neurodevelopmental nature which manifest in infancy or early childhood . The present study shows that cranium growth defects can be observed in children and adolescents with diseases or syndromes associated with neurodysfunction. The findings showed more/less common co-occurrence of as well as statistically significant relationships between: the head size - dysmorphology classification (HC), and diseases or syndromes associated with neurodysfunction, classification with regard to etiopathogenesis, presence and character of encephalopathy, epilepsy, hypothyroidism, as well as the head size - traditional classification (HC) and diseases or syndromes associated with neurodysfunction, classification with regard to etiopathogenesis, presence and character of encephalopathy, encephalopathy in neural tube defects, type of spasticity, epilepsy, and hypothyroidism.
Majority of the children presented with diseases/syndromes usually associated with encephalopathy. Encephalopathies are all kinds of conditions affecting brain structure. Depending on the patients’ age and the causes, it is possible to distinguish various types of encephalopathy [16,17]. Taking into account the character and expected presence of encephalopathy, the current study identified subjects with progressive and non-progressive encephalopathy. Only less than 10% of the children in the study group were affected by neuromuscular disorders. Given the fact that encephalopathies comprise disorders of hereditary or non-hereditary nature, i.e. congenital or acquired conditions which are primarily characterised by brain damage [16,17] and may affect the head size, it seems justified that the present findings show significant correlations of head size in both assessment systems (dysmorphology versus traditional) to the classification of the subjects based on etiopathogenesis, presence and character of encephalopathy.
The current study shows that in the group of children and adolescents with diseases or syndromes linked with neurodysfunction microcephaly is found to co-occur with epilepsy as well as hypothyroidism. Von der Hagen et al. carried out a retrospective study in a group of 680 children with microcephaly. The causes of this condition were identified in 59% of the children, and no definite diagnosis was formulated for the remaining 41%. In the former group, genetic causes were identified in approximately half of the patients, while perinatal and postnatal brain damage accounted for 45% and 3% of the cases, respectively. In the study by von der Hagen et al. epilepsy was diagnosed in 43% of the children with microcephaly . Similar results were reported by Abdel-Salam et al. Although their study involved a far smaller group, i.e. only 66 children with microcephaly, the authors also identified epilepsy in 40.9% of the children . Furthermore, it has been reported that epilepsy is more common in children with secondary microcephaly than in those with primary microcephaly [9,10]. Likewise, Ashwal et al. point out that microcephaly is associated with such comorbidities as epilepsy .
Another finding of the current study is related to co-occurrence of microcephaly and hypothyroidism in children and adolescents with diseases or syndromes associated with neurodysfunction. Research has shown that normal thyroid metabolism is necessary for human development, including the formation and functioning of the brain. However abnormal thyroid metabolism is more and more frequently diagnosed in the spectrum of paediatric neurological disorders . Kurian and Jungbluth, in their literature review investigating neurological symptoms of impaired thyroid metabolism, also point out that there is a correlation between hypothyroidism and microcephaly . A similar relationship was also reported by Carré et al. .
The current study also shows that microcephaly more commonly co-occurs with tetraplegia linked to cerebral palsy, and the former is often found to exist simultaneously with epilepsy. Occurrence of microcephaly in patients with spastic quadriplegia was reported by Cavallin et al. . Likewise, Singhi and Sain established that microcephaly is observed in 64.27% of children with cerebral palsy in North India , the most frequent type being spastic quadriplegia [21, 22]. Hadjipanayis et al. carried out a study involving 323 patients with cerebral palsy and observed that epilepsy occurred in this group at the rate of 41.8%, and in nearly one in two patients with spastic tetraplegia . In the literature it is possible to encounter reports which emphasize the fact that subjects with epilepsy are more at risk of accidental injuries, compared to individuals who do not experience seizures. The most common injuries include head contusions which consequently may lead to spastic quadriplegia .
The advantage of the present study is the fact that its findings provide unambiguous answer to the question formulated in the purpose of the study, i.e. which of the two existing criteria used in assessing cranial development defects—the system applied in dysmorphology and the one traditionally used in the clinical practice—should be employed in daily work. The presented evidence suggests greater effectiveness of the traditional classification, as it enabled identification of more relationships. Moreover, the traditional classification more effectively differentiated the links between the head size and all the subgroups distinguished based on the classification taking into account etiopathogenesis, as well as presence and character of encephalopathy.