Lacrimo‐auriculo‐dento‐digital syndrome: A novel mutation in a Korean family and review of literature

Ryu, Young Hye; Chae, Jong Kyun; Kim, Jung-Wook; Lee, Soyoung

doi:10.1002/mgg3.1412

Cited by 12 publications

(16 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lacrimo‐auriculo‐dento‐digital (LADD) syndrome is caused by loss‐of‐function mutations in FGFR2 , FGFR3 , or FGF10 (Garg & Zhang, 2017; Mikolajczak et al, 2016; Milunsky et al, 2006; Rigueur et al, 2019; Rohmann et al, 2006; Ryu et al, 2020; Talebi et al, 2017). The multiple congenital anomalies in LADD syndrome affect the lacrimal and salivary glands and ducts, ears, teeth, and distal limb segments.…”

Section: Selected Topics In Genetics Development Regeneration and Dis...mentioning

confidence: 99%

New developments in the biology of fibroblast growth factors

Ornitz

Itoh

2022

WIREs Mechanisms of Disease

View full text Add to dashboard Cite

The fibroblast growth factor (FGF) family is composed of 18 secreted signaling proteins consisting of canonical FGFs and endocrine FGFs that activate four receptor tyrosine kinases (FGFRs 1-4) and four intracellular proteins (intracellular FGFs or iFGFs) that primarily function to regulate the activity of voltagegated sodium channels and other molecules. The canonical FGFs, endocrine FGFs, and iFGFs have been reviewed extensively by us and others. In this review, we briefly summarize past reviews and then focus on new developments in the FGF field since our last review in 2015. Some of the highlights in the past 6 years include the use of optogenetic tools, viral vectors, and inducible transgenes to experimentally modulate FGF signaling, the clinical use of small molecule FGFR inhibitors, an expanded understanding of endocrine FGF signaling, functions for FGF signaling in stem cell pluripotency and differentiation, roles for FGF signaling in tissue homeostasis and regeneration, a continuing elaboration of mechanisms of FGF signaling in development, and an expanding appreciation of roles for FGF signaling in neuropsychiatric diseases.

show abstract

Section: Selected Topics In Genetics Development Regeneration and Dis...mentioning

confidence: 99%

New developments in the biology of fibroblast growth factors

Ornitz

Itoh

2022

WIREs Mechanisms of Disease

View full text Add to dashboard Cite

show abstract

“…Lacrimo-auriculo-dento-digital syndrome (LADD; MIM#149730) and aplasia of the lacrimal and salivary glands (ALSG; MIM #180920) are rare genetic diseases manifesting with variable expression and inherited in an autosomal dominant manner ( Milunsky et al, 2006 ; Ryu et al, 2020 ). LADD and ALSG belong to the same phenotypic spectrum; however, LADD patients present a more severe phenotype than individuals with ALSG ( Milunsky et al, 2006 ; Rohmann et al, 2006 ).…”

Section: Survey Methodologymentioning

confidence: 99%

Phenotypic spectrum of FGF10-related disorders: a systematic review

Bzdega¹,

Karolak²

2022

PeerJ

View full text Add to dashboard Cite

FGF10, as an FGFR2b-specific ligand, plays a crucial role during cell proliferation, multi-organ development, and tissue injury repair. The developmental importance of FGF10 has been emphasized by the identification of FGF10 abnormalities in human congenital disorders affecting different organs and systems. Single-nucleotide variants in FGF10 or FGF10-involving copy-number variant deletions have been reported in families with lacrimo-auriculo-dento-digital syndrome, aplasia of the lacrimal and salivary glands, or lethal lung developmental disorders. Abnormalities involving FGF10 have also been implicated in cleft lip and palate, myopia, or congenital heart disease. However, the exact developmental role of FGF10 and large phenotypic heterogeneity associated with FGF10 disruption remain incompletely understood. Here, we review human and animal studies and summarize the data on FGF10 mechanism of action, expression, multi-organ function, as well as its variants and their usefulness for clinicians and researchers.

show abstract

“…Bilateral dacryocele with punctal and canalicular agenesis and alacrimia form part of the lacrimoauriculardentodigital syndrome (LADD) or Levy–Hollister syndrome (MIM #149730). 19 LADD is an extremely rare autosomal dominant disorder. It results from heterozygous pathogenic variations in the tyrosine kinase domains of one of the three genes encoding either for the fibroblast growth factor (FGF) receptors FGFR2 or FGFR3 or for FGF10 , an FGFR2 ligand.…”

Section: Anatomic Anomaly: Lg Aplasia or Hypoplasia Associated With S...mentioning

confidence: 99%

“…The association of LG agenesis, dacryocystocele, and an abnormal lacrimal system is highly suggestive of LADD, even in the absence of other typical symptoms of the syndrome. 19 …”

Section: Anatomic Anomaly: Lg Aplasia or Hypoplasia Associated With S...mentioning

confidence: 99%

“…Although the FGF10 pathogenic variations cause haploinsufficiency, the FGFR2b LADD mutants may exert a dominant negative interfering effect on signaling via normal FGFR2b, causing LADD, contrary to the dominant activating effect of FGFR2 pathogenic variations implicated in craniosynostosis. In a patients with LADD and his mildly affected father, Ryu et al 19 identified a heterozygous missense variation of FGFR2 : c.1547C>T (p.Ala516Val); however, the functional consequences of this variation on the protein activity were neither studied nor discussed. The authors considered this variation as probably pathogenic, because the clinical phenotype of LADD was established in this family.…”

Section: Anatomic Anomaly: Lg Aplasia or Hypoplasia Associated With S...mentioning

confidence: 99%

See 1 more Smart Citation

Hypolacrimia and Alacrimia as Diagnostic Features for Genetic or Congenital Conditions

Willems

Wells

Coubes

et al. 2022

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

As part of the lacrimal apparatus, the lacrimal gland participates in the maintenance of a healthy eye surface by producing the aqueous part of the tear film. Alacrimia and hypolacrimia, which are relatively rare during childhood or young adulthood, have their origin in a number of mechanisms which include agenesia, aplasia, hypoplasia, or incorrect maturation of the gland. Moreover, impaired innervation of the gland and/or the cornea and alterations of protein secretion pathways can lead to a defective tear film. In most conditions leading to alacrimia or hypolacrimia, however, the altered tear film is only one of numerous defects that arise and therefore is commonly disregarded. Here, we have systematically reviewed all of those genetic conditions or congenital disorders that have alacrimia or hypolacrimia as a feature. Where it is known, we describe the mechanism of the defect in question. It has been possible to clearly establish the physiopathology of only a minority of these conditions. As hypolacrimia and alacrimia are rare features, this review could be used as a tool in clinical genetics to perform a quick diagnosis, necessary for appropriate care and counseling.

show abstract

Lacrimo‐auriculo‐dento‐digital syndrome: A novel mutation in a Korean family and review of literature

Cited by 12 publications

References 42 publications

New developments in the biology of fibroblast growth factors

New developments in the biology of fibroblast growth factors

Phenotypic spectrum of FGF10-related disorders: a systematic review

Hypolacrimia and Alacrimia as Diagnostic Features for Genetic or Congenital Conditions

Contact Info

Product

Resources

About