Macroglossia is a clinically significant feature of Beckwith-Wiedemann syndrome (BWS), but the cellular basis of tongue overgrowth remains poorly defined. Using pediatric tongue specimens from molecularly defined BWS subtypes and age-matched nonBWS controls, we show that BWS macroglossia is characterized by skeletal muscle fiber hypertrophy rather than increased fiber number. This phenotype is not explained by expansion or increased proliferation of satellite cells in situ, and isolated tongue satellite cells do not exhibit enhanced proliferation under growth conditions in vitro. Instead, BWS progenitors adopt distinct differentiation-associated regulatory states. Imprinting control region 2 (IC2) loss-of-methylation cells sustain proliferative activity during differentiation and form enlarged myotubes, consistent with a cell-autonomous hypertrophic program. In contrast, paternal uniparental disomy of chromosome 11 (pUPD11) cells display NOTCH pathway activation and progenitor-associated programs, with attenuated progression toward terminal myogenic differentiation. Together, these findings identify subtype-specific myogenic states that converge on a shared hypertrophic tissue phenotype in BWS macroglossia.

Amyloidosis is a heterogeneous disease that results from the deposition of toxic insoluble beta-sheet fibrillar protein aggregates in different tissues. Amyloidosis can be acquired or hereditary. The disease can be localized or systemic. Amyloid can accumulate in the liver, spleen, kidney, heart, nerves, and blood vessels, causing different clinical syndromes, including cardiomyopathy, hepatomegaly, proteinuria, macroglossia, autonomic dysfunction, ecchymoses, neuropathy, renal failure, hypertension, and corneal and vitreous abnormalities. Previously multiple classification systems have been devised to classify different types of amyloidosis. In modern times it has been classified according to the chemical analysis of amyloid clinical entities. Amyloidosis can be classified according to systemic, hereditary, central nervous system, ocular, and localized etiology. However, the most common types are AL, AA, ATTR (amyloid transport protein transthyretin), and dialysis-related amyloidosis (beta2M type). In AL amyloidosis, 'A' represents amyloid followed by the associated fibrillar protein, 'L' means light chain fragment or immunoglobulin light chain. In AA amyloidosis, the second A stands for the serum amyloid A protein.

Lymphatic malformations are rare congenital vascular anomalies that most commonly affect the head and neck regions. Cervicofacial lesions extending into the oral cavity or upper airway can result in dysphagia, bleeding, malnutrition, and airway obstruction. Emergency assessment is particularly challenging because significant anatomic distortion can exist even when physiologic parameters remain stable, necessitating thorough airway evaluation and early anticipation of potential clinical deterioration.

Beckwith-Wiedemann syndrome (BWS) is a rare congenital disorder whose main clinical feature is macroglossia. This frequent manifestation may impair respiratory, feeding, speech, and orofacial developmental functions. When significant functional and/or aesthetic repercussions are evident, surgical excision is the primary management approach, with several techniques described. In this study, we analyzed medical records from 29 patients diagnosed with BWS and macroglossia, and evaluated 26 cases of partial glossectomy performed between 2015 and 2025. Indications, surgical technique, postoperative course, and short-term and medium-term outcomes are discussed, emphasizing the importance of early and standardized intervention. A new clinical grading for macroglossia was developed in BWS. All procedures were performed by a single surgeon in a craniofacial surgery reference center in Southern Brazil, with patients aged between 5 months and 8.9 years. Epidemiologically, 65.4% of the patients were female and the average age of surgery was 18.5 months, the median was 10 months. Macroglossia was classified as mild in 11.5%, moderate in 46.2% and severe in 42.3% of cases. The average tongue reduction was 31.6% in length and 21% in width. Retrospective analysis of medical records demonstrated appropriate functional improvement, a low complication rate, and satisfactory aesthetic and respiratory outcomes in most cases. The findings reinforce the safety and effectiveness of partial glossectomy in managing macroglossia associated with BWS.

Beckwith-Wiedemann spectrum (BWSp) is an overgrowth disorder characterized by its main clinical features macrosomia, macroglossia, and abdominal wall defects. BWSp is caused by (epi)genetic chromosome 11p15 alterations with approximately 20%-27% of patients exhibiting mosaic paternal uniparental disomy of chromosome 11p15 (pUPD11p15). In this study, we analyzed 46 newly identified patients with pUPD11p15. We investigated the ratio of mosaicism and the extent of pUPD11(p15) segment length and explored their correlation with the clinical phenotype. Additionally we compared the cardinal and suggestive features of our cohort with previously reported pUPD11p15 patients in the literature. The most common phenotypes in our cohort were lateralized overgrowth, organomegaly and macroglossia. While no correlation was found between the segment length and clinical phenotype, a significant positive correlation was observed between the BWSp clinical score and mosaic ratio in blood. This correlation was primarily driven by macroglossia. In contrast to previously published studies reporting mosaic genome-wide paternal UPD (MGWpUPD) in 2%-19% of patients with pUPD11 and BWSp, this was not detected in our cohort.

Down syndrome (DS) is the most common chromosomal disorder associated with intellectual disability and is marked by a wide array of systemic, craniofacial, and oral manifestations. Children with DS often present with dental anomalies and a range of medical comorbidities that significantly affect oral health and dental management. This review provides a comprehensive analysis of the dental, craniofacial, airway, and anesthetic challenges commonly encountered in children with DS, highlighting their practical implications for contemporary dental practice. This narrative review synthesizes published studies, clinical guidelines, and review articles on oral health, craniofacial features, airway abnormalities, and perioperative considerations in children with DS. The synthesized evidence serves as a concise, practical resource for general dental practitioners. Children with DS frequently exhibit delayed tooth eruption, hypodontia, abnormal tooth morphology, bruxism, periodontal disease, and malocclusion. Distinct craniofacial features, including relative macroglossia, midface hypoplasia, and a high-arched palate, pose substantial functional and orthodontic challenges. Obstructive sleep apnea (OSA) is common and can complicate airway management during sedation and general anesthesia. Additionally, conditions such as atlantoaxial instability (AAI) and congenital heart disease (CHD) require meticulous preoperative assessment and coordinated multidisciplinary care. Although dental caries rates may be similar to or lower than those in the general population, periodontal disease remains a principal source of oral morbidity. Children with DS present with distinct oral, craniofacial, and medical characteristics that necessitate tailored dental care. Early implementation of preventive measures, ongoing dental monitoring, and robust collaboration among dental and medical professionals are essential for optimizing oral health, ensuring safe and effective treatment, and enhancing quality of life.

6q24-related transient neonatal diabetes mellitus (6q24-TNDM) is defined as transient neonatal diabetes mellitus caused by genetic aberrations of the imprinted locus at 6q24. The cardinal features are: severe intrauterine growth retardation, hyperglycemia that begins in the neonatal period in a term infant and resolves by age 18 months, dehydration, and absence of ketoacidosis. Macroglossia and umbilical hernia may be present. 6q24-TNDM associated with a multilocus imprinting disturbance (MLID) can be associated with marked hypotonia, congenital heart disease, deafness, neurologic features including epilepsy, and renal malformations. Diabetes mellitus usually starts within the first week of life and lasts on average three months but can last longer than a year. Although insulin is usually required initially, the need for insulin gradually declines over time. Intermittent episodes of hyperglycemia may occur in childhood, particularly during intercurrent illnesses. Diabetes mellitus may recur in adolescence or later in adulthood. Women who have had 6q24-TNDM are at risk for relapse during pregnancy.

Presentation of Beckwith-Wiedemann syndrome (BWS) is widely variable. Congenital adrenal hyperplasia (CAH) is the leading cause of atypical genitalia in the female newborn. Beckwith-Wiedemann syndrome was previously not recognized as a possible cause of a false diagnosis of CAH. A late preterm (gestational age of 36 weeks) female presented at the 3[rd] hour of life with an anterior abdominal wall defect and swelling. Examination revealed coarse facial features, macroglossia, omphalocele major, prominent labia majora with hyperpigmented and enlarged clitoris. Weight was >97[th] percentile for age and sex, with length and occipitofrontal circumference at 95[th] and 50[th] percentiles, respectively. Initial blood investigations revealed hypoglycaemia, hyponatraemia, hypocortisolaemia, elevated testosterone and 17-hydroxyprogesterone with female internal genitalia suggesting CAH. She was commenced on hydrocortisone. Omphalocele was managed conservatively. Abdominal ultrasound scan showed no enlargement of the adrenal glands or tumours. Genetic analysis showed hypomethylation at KCNQ1OT1: TSS-DMR (IC2) within 11p15.5, confirming a diagnosis of BWS. Clitoromegaly resolved spontaneously at six months of life without any surgical intervention, with normal pigmentation of the external genitalia. Steroids were tapered off, and repeat adrenal metabolites are normal. BWS may present with transient features suggestive of CAH.

Lymphangiomas are uncommon congenital benign tumors of the lymphatic system. They are typically diagnosed at birth and develop during the first years of life. The tongue is the most commonly affected structure in the oral cavity. Lymphangioma circumscriptum of the tongue is a common cause of macroglossia in children, and this macroglossia can lead to complications such as exclusive nasal breathing, airway obstructions, impaired oral feeding, esthetic disfigurement, and difficulties in mastication, swallowing, and speech. This report discusses the successful treatment of lymphangioma circumscriptum of the tongue with sirolimus, an immunosuppressant drug. The extent of the lesion made traditional surgical management impossible without excessive morbidity, so the patient was managed medically. This case report was unique due to its entirely nonsurgical treatment approach. The patient completed a 17-month course of sirolimus monotherapy with response to treatment monitored using T2 MRI. There was excellent response to treatment, full resolution of symptoms, and no treatment-related toxicity.

A 1-year-old, male castrated domestic shorthair cat presented for chronic mobility decline and muscle stiffness, first noted at 3 months of age, and persistently elevated serum creatine kinase levels (>19,000-53,000 IU/l). Clinical examination revealed macroglossia and selective hypertrophy of cervical and appendicular muscles. Neurologic evaluation indicated a myopathic gait without pain or neurologic deficits. Muscle biopsy was supportive of muscular dystrophy (MD) and immunohistochemistry demonstrated loss of the sarcoglycan complex with complete absence of all tested sarcoglycan proteins, consistent with a diagnosis of sarcoglycan-deficient MD. These findings contrast with prior feline reports that were mostly limited to reduction or absence of beta-sarcoglycan on immunostaining without overt clinical evidence of MD. A follow-up echocardiogram revealed mild to moderate right ventricular changes without indications for treatment. At 2 months after diagnosis, the patient remained clinically static, suggesting a relatively slow progression despite absent sarcoglycan expression.