Aplasia Of Salivary Glands Research Articles

Fibroblast growth factor 10

Fibroblast growth factor 10 (FGF10) is a major morphoregulatory factor that plays essential signaling roles during vertebrate multiorgan development and homeostasis. FGF10 is predominantly expressed in mesenchymal cells and signals though FGFR2b in adjacent epithelia to regulate branching morphogenesis, stem cell fate, tissue differentiation and proliferation, in addition to autocrine roles. Genetic loss of function analyses have revealed critical requirements for FGF10 signaling during limb, lung, digestive system, ectodermal, nervous system, craniofacial and cardiac development. Heterozygous FGF10 mutations have been identified in human genetic syndromes associated with craniofacial anomalies, including lacrimal and salivary gland aplasia. Elevated Fgf10 expression is associated with poor prognosis in a range of cancers. In addition to developmental and disease roles, FGF10 regulates homeostasis and repair of diverse adult tissues and has been identified as a target for regenerative medicine.

Partial penetrance and phenotypic variability of aplasia of lacrimal and salivary glands caused by a novel FGF10 donor splice-site mutation.

Thirteen affected individuals of six generations of a single kindred presented with epiphora evident from infancy. Physical exam and Schirmer test revealed variable expression of tear deficiency, congenital punctal atresia, and dry mouth with multiple caries, without concomitant abnormalities of the ears or digits, commensurate with a diagnosis of aplasia of the lacrimal and salivary glands (ALSG). Reconstruction of the upper lacrimal drainage system was performed in some of the affected individuals. Genetic analysis, testing six affected individuals and three non-affected family members, identified a single novel heterozygous splice-site variant, c.429 + 1, G > T in fibroblast growth factor 10 (FGF10) (NM_004465.1), segregating throughout the family as expected for dominant heredity. RT-PCR assays of HEK-293 cells transfected with wild type or mutant FGF10 demonstrated that the variant causes skipping of Exon 2. Notably, individuals sharing the same variant exhibited phenotypic variability, with unilateral or bilateral epiphora, as well as variable expression of dry mouth and caries. Moreover, one of the variant carriers had no ALSG-related clinical findings, demonstrating incomplete penetrance. While coding mutations in FGF10 are known to cause malformations in the nasolacrimal system, this is the second FGF10 splice-site variant and the first donor-site variant reported to cause ALSG. Thus, our study of a unique large kindred with multiple affected individuals heterozygous for the same FGF10 variant highlights intronic splice-site mutations and phenotypic variability/partial penetrance in ALSG.

Dry mouth in children: an under-reported condition?

Abstract: Dry mouth has a profound effect on the oral environment and alters susceptibility to oral disease. It is well-recognized in adults but affected children may not report symptoms even when severe oral dryness is present, potentially leading to late diagnosis and missed opportunities to prevent caries and other adverse sequelae. This article describes the causes and clinical signs of salivary hypofunction in children and young people and documents some associated emotional and social impacts on patients and their families. It is illustrated by four cases where the underlying diagnoses were 22q11 micro-deletion syndrome, congenital salivary gland aplasia, sarcoidosis and medication-induced. CPD/Clinical Relevance: An awareness of the possible presentations, underlying causes and impacts of dry mouth in children and young people will enable vigilant dental practitioners to diagnose the problem at an earlier stage, so that appropriate enhanced preventive care and additional support can be offered promptly.

Fgf10: a paracrine-signaling molecule in development, disease, and regenerative medicine.

The Fgf family comprises 22 members with diverse functions in development, repair, metabolism, and neuronal activities. Fgf10 mediates biological responses by activating Fgf receptor 2b (Fgfr2b) with heparin/heparan sulfate in a paracrine manner. Fgf10 and Fgfr2b are expressed in mesenchymal and epithelial tissues, respectively. Fgf10 is an epithelial-mesenchymal signaling molecule. Fgf10 knockout mice show severe phenotypes with complete truncation of the fore- and hindlimbs and die shortly after birth due to impaired lung development, indicating that Fgf10 serves as an essential regulator of lung and limb formation. Fgf10 also has roles in the development of white adipose tissue, heart, liver, brain, kidney, cecum, ocular glands, thymus, inner ear, tongue, trachea, eye, stomach, prostate, salivary gland, mammary gland, and whiskers. The diverse phenotypes of Fgf10 knockout mice are closely related to those of Fgfr2 knockout mice, suggesting that Fgf10 acts as a major ligand for Fgfr2b in mouse multi-organ development. Aplasia of lacrimal and salivary glands and lacrimo-auriculo-dento-digital syndrome are caused by Fgf10 mutations in humans. Variants in Fgf10 may be involved in an increased risk for limb deficiencies and cleft lip and palate. Patients with Fgf10 haploinsufficiency have lung function parameters indicating chronic obstructive pulmonary disease. Fgf10 induces migration and invasion in pancreatic cancer cells. Fgf10 signaling may be involved in an increased risk for breast cancer. Fgf10 also induces the differentiation of embryonic stem cells into a gut-like structure, cardiomyocytes, and hepatocytes. These findings indicate the crucial roles of Fgf10 in development, disease, and regenerative medicine.

Hyposalivation in a 16‐year‐old girl: a case of salivary gland aplasia

Salivary gland aplasia is a rare condition with only a small number of cases reported worldwide. It is more commonly seen in males and can occur either in isolation or association with other defects or syndromes. It may or may not occur with a hereditary background. Scant literature exists detailing the status of sublingual salivary glands in patients with any form of major salivary gland aplasia. This case report describes the clinical and magnetic resonance imaging presentation of a 16-year-old girl with major salivary gland aplasia detailing the status of all six major salivary glands.

Non-syndromic non-familial bilateral parotid and submandibular salivary gland aplasia with lacrimal duct atresia: A rare congenital ectodermal defect

Salivary gland agenesis is a rare disorder, which can appear singly or in combination with other genetic disorders. Bilateral parotid and submandibular salivary gland aplasia is an extremely rare condition found to be associated with mutation of gene encoding fibroblast growth factor (FGF) 10. Here, we present a rare case of non-syndromic non-familial bilateral parotid and submandibular salivary gland aplasia with lacrimal duct atresia in a 7-year-old male patient.

Non-Syndromic Non-Familial Agenesis of Major Salivary Glands: A Report of Two Cases with Review of Literature

Agenesis of the major salivary glands is a rare and unusual condition, with only a few cases documented in the literature. The anomaly can be total or partial, unilateral or bilateral, and involve the parotid, submandibular, and sublingual glands. The resultant xerostomia leads to extensive dental demineralization. The authors report two cases with decreased saliva volume, impaired dental condition with extensive loss of tooth structure, and an astonishing pattern of dental destruction most notable on the facial and lingual surfaces of incisors and canines that can be best described as “chipping.” After detailed review of patient history, clinical examination, ultrasonography, contrast enhanced computed tomography, and magnetic resonance imaging a diagnosis of congenital absence of major salivary glands in both the patients was made. Dentists should be aware that salivary gland aplasia is an uncommon cause of dental deterioration. It may manifest itself not by extensive caries but as dental chipping effect. Early recognition and a therapeutic strategy can prevent further dental damage.

Recurrent right sublingual ranula, concomitant with ipsilateral submandibular salivary gland aplasia

INTRODUCTIONOral ranula is a retention cyst that arises from the salivary gland with recurrence rate of up to 25% after complete excision of ranula and up to 2% in case of complete excision of ranula and sublingual gland.Major salivary gland aplasia is a rare finding that is usually associated with other developmental anomalies. PRESENTATION OF CASEWe report a 15-year-old female patient presented with recurrent intraoral cystic swelling that was documented to be sublingual ranula. CT scan revealed also the absence of right submandibular salivary gland with persistence of its Whartons duct. This combination has never been reported previously. DISCUSSIONThe combination of recurrent sublingual ranula associated with aplasia of ipsilateral submandibular salivary gland and persistence of Whartons duct has never been reported before in the literature, a finding that may provide the base for future research. CONCLUSIONFurther research may prove similar associations between oral ranula and salivary gland aplasia, which may have clinical implications on diagnostic and management plan decisions.

Unilateral submandibular gland aplasia with ipsilateral sublingual gland hypertrophy presenting as a neck mass

The congenital absence of the major salivary glands is a very infrequent disorder, in which several glands are usually involved at the same time. Sometimes this disorder can be associated with other developmental anomalies. The unilateral aplasia of the submandibular gland is an extremely rare finding with only 14 cases reported in the literature. Clinically, this kind of patients may complain of dryness of the mouth, difficulties in chewing and swallowing, severe periodontal disease or multiple caries, but usually they follow an asymptomatic course. Salivary gland aplasia can be diagnosed with a large variety of imaging techniques, which include computer tomography (CT), magnetic resonance imaging (MR), ultrasonography (US), sialography, or scintigraphy. In this paper we report a case of a patient referred to our department with a long term and progressive growing neck mass, who has an unilateral submandibular gland aplasia associated to an ipsilateral hypertrophy of the sublingual gland.

Case report: Aplasia of the lacrimal and major salivary glands (ALSG)

Aplasia of the lacrimal and major salivary glands (ALSG) is a rare, autosomal dominant disorder that is characterized by aplasia, atresia, or hypoplasia of the lacrimal and salivary glands. Affected patients may have aplasia or hypoplasia or minimal involvement of these glands, as there is considerable variation in expressivity [M. Entesarian, et al., Mutations in the gene encoding fibroblast growth factor 10 are associated with aplasia of lacrimal and salivary glands, Nat. Genet. 37 (2) (2005) 125–127]. The underlying cause has been linked to “loss of function” mutations in the fibroblast growth factor 10 (FGF10) gene [M. Entesarian, et al., FGF10 missense mutations in aplasia of lacrimal and salivary glands (ALSG), Eur. J. Hum. Genet. 15 (3) (2007) 379–382]. Lacrimal gland absence or hypoplasia causes symptoms such as irritable eyes, recurrent eye infections and epiphora. Symptoms associated with hypoplasia or aplasia of the major salivary glands include xerostomia, oral inflammation, dental caries and dental erosion. Other clinical signs of this disorder include atresia of nasolacrimal duct and absence of the lacrimal puncta. Unfortunately, genetic testing for this disorder is currently unavailable. However, MRI is an excellent alternative means for evaluating this disorder and also for ruling out other possible structural defects contributing to patients, symptoms. We present a case report of ALSG as an extremely rare, yet important alternative diagnosis in cases with symptoms and signs suggestive of Sjögren's syndrome.

An intronic alteration of the fibroblast growth factor 10 gene causing ALSG-(aplasia of lacrimal and salivary glands) syndrome

BackgroundA combined aplasia, hypoplasia or atresia of lacrimal points and salivary glands is rarely diagnosed. Those patients suffer from epiphora, xerostomia and severe dental caries. This phenotype represents the autosomal-dominant aplasia of lacrimal and salivary glands syndrome (ALSG). Recently, aberrations of the Fibroblast Growth Factor 10 (FGF10) gene have been identified to be causative for this disorder.MethodsWe performed a sequence analysis of the FGF10 gene of a patient with ALSG-syndrome and his also affected brother as well as 193 controls. The FGF10 transcript was analyzed using RNA extracted from primary fibroblasts of the patient's mucosa.ResultsWe detected a novel heterozygous sequence variation in intron 2 (c.430-1, G > A) causing the ALSG syndrome. The alteration derogates the regular splice acceptor site and leads to the use of a new splice acceptor site 127 bp upstream of exon 3. The aberration was detected in the genomic DNA derived from two affected brothers, but not in 193 control individuals. Furthermore, no diseased member of the family displayed additional abnormalities that are indicative for the clinically overlapping lacrimo-auriculo-dento-digital syndrome (LADD).ConclusionThis family-based approach revealed an intronic variation of the FGF10 gene causing ALSG-syndrome. Our results expand the mutational and clinical spectrum of the ALSG syndrome.

Unilateral submandibular gland aplasia masquerading as cancer nodal metastasis

Objective Five reports have examined unilateral submandibular gland aplasia. The purposes of this report are to demonstrate submandibular gland aplasia leading to contralateral gland hypertrophy in the setting of oral cavity cancer and to discuss the corresponding diagnostic and management challenges. Study design This study is a case report of a 60-year-old male who presented with pain on the right side of the mobile tongue. Method This report uses literature review. Results A 60-year-old male presented with pain on the right side of the mobile tongue. Subsequent results of punch biopsy revealed squamous cell carcinoma in situ with foci of microinvasion of the tongue. Head and neck examination revealed no abnormalities. The patient underwent a wide-local excision of the tongue lesion. Postoperative computed tomographic (CT) scan showed an asymmetric mass on the ipsilateral side of the cancer in the region of the submandibular gland. The gland was noted to be abnormally large. A diagnosis of contralateral submandibular gland aplasia was made. The patient is cancer-free at 2 years postlocal excision. Salivary gland aplasia is an extremely rare disorder and is often associated with various congenital syndromes. Unilateral submandibular gland aplasia is even rarer with ours representing the sixth reported case. Aplasia is believed to stem from a regional disturbance in early fetal development. Common symptoms can include dysphagia, dry mouth, decreased taste, and tooth decay. In the presence of a history of oral cavity cancer, unilateral submandibular gland aplasia poses a challenge during postoperative cancer follow-up. Conclusions Unilateral submandibular gland aplasia in the setting of oral cavity cancer poses a unique challenge for cancer follow-up. Hypertrophy of the submandibular gland on the other side can masquerade as nodal metastasis. Head and neck examination as well as CT scan can be inconclusive. Regular confirmatory tests such as fine needle aspiration biopsy and positron emission tomography/CT for cancer detection is extremely useful for detecting recurrence.

FGF10 missense mutations in aplasia of lacrimal and salivary glands (ALSG)

Aplasia of lacrimal and salivary glands (ALSG) is an autosomal dominant congenital anomaly characterized by aplasia, atresia or hypoplasia of the lacrimal and salivary systems. Affected individuals present with irritable eyes and dryness of the mouth with variable expressivity. Mutations in FGF10 were recently described in ALSG and in lacrimo-auriculo-dento-digital (LADD) syndrome which are overlapping clinical entities. We present here two families with ALSG associated with missense mutations (R80S and G138E, respectively) affecting highly conserved residues in FGF10. The clinical features of these patients further broaden the knowledge of FGF10-related phenotypes.

FGF signalling in craniofacial development and developmental disorders

The Fgf signalling pathway is highly conserved in evolution and plays crucial roles in development. In the craniofacial region, it is involved in almost all structure development from early patterning to growth regulation. In craniofacial skeletogenesis, the Fgf signal pathway plays important roles in suture and synchondrosis regulation. Mutations of FGF receptors relate to syndromatic and non-syndromatic craniosynostosis. The Fgf10/Fgfr2b signal loop is critical for palatogenesis and submandibular gland formation. Perturbation of the Fgf signal is a possible mechanism of palatal cleft. Fgf10 haploinsufficiency has been identified as the cause of autosomal dominant aplasia of lacrimal and salivary glands. The Fgf signal is also a key regulator of tooth formation: in the absence of Fgfr2b tooth development is arrested at the bud stage. Fgfr4 has recently been identified as the key signal mediator in myogenesis. In this review, these aspects are discussed in detail with a focus on the most recent advances.

A case of major salivary gland agenesis

Major salivary gland agenesis is a rare disorder and only a few instances of the condition have been reported. The number of absent salivary glands and the degree of associated xerostomia vary between individuals. Salivary gland agenesis can cause profound xerostomia in children and there may be oral and upper respiratory tract sequelae, such as dental caries, candidiasis, ascending sialadenitis, laryngitis and pharyngitis. Salivary gland aplasia may be associated with other ectodermal defects, particularly abnormalities of the lacrimal apparatus. We report on the first observation of major salivary gland agenesis in South Korea. A child with xerostomia should be appropriately investigated and diagnosed, and careful attention should be paid to the prevention and treatment of sequelae.

Mutations in the gene encoding fibroblast growth factor 10 are associated with aplasia of lacrimal and salivary glands

Autosomal dominant aplasia of lacrimal and salivary glands (ALSG; OMIM 180920 and OMIM 103420) is a rare condition characterized by irritable eyes and dryness of the mouth. We mapped ALSG to 5p13.2-5q13.1, which coincides with the gene fibroblast growth factor 10 (FGF10). In two extended pedigrees, we identified heterozygous mutations in FGF10 in all individuals with ALSG. Fgf10(+/-) mice have a phenotype similar to ALSG, providing a model for this disorder. We suggest that haploinsufficiency for FGF10 during a crucial stage of development results in ALSG.

Aplasia of the parotid gland in Down syndrome

Salivary gland aplasia has not to our knowledge been previously reported in association with Down syndrome. We present a case of bilateral parotid aplasia in a patient with Down syndrome. Clinically he had aplasia of the major salivary glands and symptoms of xerostomia. Thirteen other family members over three generations were examined, and all had functional parotid glands. We reviewed publications about Down syndrome and salivary aplasia, together with the data regarding his other clinical problems and family background. His oral problems were inadequate plaque control, dental caries, and erosion of the teeth.

Salivary gland aplasia with cleft lip and palateA case report and review of the literature

We report the case of a patient with lifelong symptoms of xerostomia and a repaired bilateral cleft lip and palate. The clinical evaluation demonstrated aplasia of the major salivary glands. A review of the literature pertaining to salivary gland aplasia is presented, along with a summary of the data regarding patient gender, defect sites, hereditary background, and combined manifestations. The diagnostic methods, possible pathogenesis, and management are also discussed. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87:594-9)

Major salivary gland dysfunction: Report of a case

A case of major salivary gland dysfunction is presented. From the history elicited from the patient and from the clinical findings, this case could not be called hereditary ectodermal dysplasia, major salivary gland aplasia, or atresia. Because of the extreme rareness of cases of the latter two entities a review of the literature was very difficult and yielded meager results. Two related articles have been reviewed, one concerning three cases of major salivary gland dysfunction and one concerning a case of congenital imperforate submandibular ducts.