Overview
Carbuncle of the temple region, often associated with broader clinical syndromes such as Temple syndrome (TS14), encompasses a constellation of developmental and physical anomalies primarily linked to chromosomal abnormalities, particularly involving chromosome 14. This condition is characterized by a complex genetic background, including de novo chromosomal rearrangements and copy-number variations, which contribute to a diverse range of clinical manifestations. Patients typically present with severe intellectual disability, distinctive physical features, and growth deficiencies, necessitating a multidisciplinary approach to management. Understanding the underlying genetic mechanisms is crucial for accurate diagnosis and tailored therapeutic interventions, particularly growth hormone (GH) therapy, which has shown promising outcomes in improving growth parameters.
Pathophysiology
The pathophysiology of carbuncle of the temple region, often seen in the context of Temple syndrome, involves intricate genetic alterations that disrupt normal developmental processes. A notable genetic finding is the identification of a de novo 2.2-Mb triplication on chromosome 14, followed by 42.2 Mb of copy-number neutral uniparental disomy (UPD) on the same chromosome in affected individuals [PMID:31014393]. This chromosomal rearrangement is hypothesized to disrupt critical genes essential for neurodevelopment and growth regulation, leading to the characteristic clinical features observed in Temple syndrome. Additionally, mutations in specific genes, such as the KCNH1 gene, have been implicated. For instance, an iPSC line (ZJUCHi003) derived from a patient harboring the KCNH1 c.1070G > A (p.R357Q) variant demonstrated altered neuronal electrophysiological properties, including slower repolarization and wider action potential half-width compared to normal neurons [PMID:38372889]. These cellular-level disruptions likely contribute to the neurological deficits and developmental delays seen in patients, underscoring the multifaceted genetic basis of the syndrome.
Clinical Presentation
Patients with carbuncle of the temple region typically present with a range of clinical features that overlap significantly with Temple syndrome, characterized by UPD(14)mat. These features often include severe intellectual disability, distinctive facial anomalies (such as a prominent forehead and midface hypoplasia), and various physical anomalies [PMID:31014393]. The proband in the study exhibited overlapping clinical features, highlighting the phenotypic spectrum associated with UPD(14)mat. Additionally, patients frequently manifest growth deficiencies, with initial height standard deviation scores (SDS) often significantly below average, such as -1.78 in some cases [PMID:36977395]. Seizures and other neurological symptoms are also common, aligning with the findings from the KCNH1 variant study, where recurrent pathogenic variants led to features consistent with Temple-Baraitser/Zimmermann-Laband syndrome, including severe mental retardation, seizures, and physical anomalies [PMID:38372889]. These clinical presentations underscore the need for early recognition and comprehensive management to address both developmental and physical challenges.
Diagnosis
Diagnosing carbuncle of the temple region involves a combination of clinical evaluation and advanced genetic testing. Family-based genomic analyses have been pivotal in identifying the underlying genetic causes, particularly the de novo triplication and UPD(14)mat on chromosome 14, confirmed through characteristic methylation patterns typical of UPD(14)mat patients [PMID:31014393]. Genetic testing, including chromosomal microarray analysis (CMA) and targeted sequencing, is essential for detecting these specific chromosomal rearrangements and gene mutations. The identification of the KCNH1 c.1070G > A (p.R357Q) variant through genetic analysis was crucial not only for establishing the diagnosis but also for generating induced pluripotent stem cell (iPSC) lines that further elucidate the cellular mechanisms underlying the syndrome [PMID:38372889]. These diagnostic approaches help differentiate Temple syndrome from other overlapping syndromes and guide appropriate management strategies.
Management
The management of carbuncle of the temple region focuses on addressing the multifaceted aspects of the condition, with a particular emphasis on growth deficiencies and neurological support. Growth hormone (GH) therapy has emerged as a cornerstone intervention, demonstrating significant benefits in improving growth parameters. Studies have shown that GH treatment led to substantial increases in mean height SDS, from an initial deficit of -1.78 to a more normalized score of 0.11, alongside improvements in lean body mass (LBM) SDS and LBM index in children with TS14 [PMID:36977395]. This therapy not only enhances physical growth but also positively impacts overall body composition, contributing to better health outcomes. Additionally, supportive care includes management of seizures with appropriate anticonvulsants, cognitive interventions, and physical therapy to address motor skill development and coordination issues. Multidisciplinary teams, including geneticists, neurologists, endocrinologists, and developmental specialists, play a crucial role in tailoring comprehensive care plans for these patients.
Prognosis & Follow-up
The prognosis for individuals with carbuncle of the temple region varies but is generally influenced by the severity of the underlying genetic abnormalities and the effectiveness of interventions such as GH therapy. In prepubertal patients treated with GH, follow-up studies indicate sustained improvements in height SDS, LBM SDS, and LBM index over time, with resting energy expenditure remaining relatively stable during the initial year of treatment [PMID:36977395]. These outcomes suggest that early and sustained GH therapy can significantly mitigate growth deficiencies. Long-term follow-up is essential to monitor continued growth patterns, cognitive development, and overall health status. Regular assessments by a multidisciplinary team can help adjust treatment plans as needed and provide ongoing support to optimize quality of life for affected individuals.
Special Populations
Special considerations are necessary for specific subpopulations within this patient cohort, particularly prepubertal patients who are candidates for GH therapy. Data from studies involving prepubertal patients treated with GH reveal positive growth outcomes, with five patients reaching adult height achieving a median height SDS of 0.67, indicating that early intervention can lead to near-normal adult stature [PMID:36977395]. These findings highlight the importance of initiating GH therapy at an early age to maximize growth potential. Additionally, the unique challenges faced by these patients, including complex care needs and potential psychosocial impacts, necessitate tailored support systems, including psychological counseling and social services, to address the holistic well-being of the individual.
Key Recommendations
These recommendations are based on current evidence and expert opinion, emphasizing the importance of early intervention and comprehensive care to optimize outcomes for patients with carbuncle of the temple region.
References
1 Carvalho CMB, Coban-Akdemir Z, Hijazi H, Yuan B, Pendleton M, Harrington E et al.. Interchromosomal template-switching as a novel molecular mechanism for imprinting perturbations associated with Temple syndrome. Genome medicine 2019. link 2 Chen D, Su J, Huang X, Chen H, Jiang T, Zhi C et al.. Establishment and characterization of ZJUCHi003: an induced pluripotent stem cell line from a patient with Temple-Baraitser/Zimmermann-Laband syndrome carrying KCNH1 c.1070G > A (p.R357Q) variant. Human cell 2024. link 3 Juriaans AF, Trueba-Timmermans DJ, Kerkhof GF, Grootjen LN, Walet S, Sas TCJ et al.. The Effects of 5 Years of Growth Hormone Treatment on Growth and Body Composition in Patients with Temple Syndrome. Hormone research in paediatrics 2023. link
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