Lacrimo-Auriculo-Dento-Digital Syndrome with Unilateral Inner Ear Dysplasia and Craniocervical Osseous Abnormalities: Case Report and Review of Literature

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

“…Previously reported cases had indicated varied phenotypes, including facial dysmorphism, genitourinary and renal anomalies, gastrointestinal symptoms, skeletal involvement other than digital or limb involvement, and airway involvement. Twenty‐three previous case reports and case series are summarized in Table 1 (Azar, Arnold, Scott, & Robin, 2000; Guven, Rosti, Tuna, Kayserili, & Aktoren, 2008; Hajianpour et al, 2017; Haktanir, Degirmenci, Acar, Albayrak, & Yucel, 2005; Hollister et al, 1973; Inan et al, 2006; Kreutz & Hoyme, 1988; Lacombe et al, 1993; Lehotay, Kunkel, & Wehrbein, 2004; Levy, 1967; Mathrawala & Hegde, 2011; McKenna, Burke, & Mellan, 2009; Meuschel‐Wehner, Klingebiel, & Werbs, 2002; Milunsky, Zhao, Maher, Colby, & Everman, 2006; Moses, 2013; Ostuni et al, 1995; Pathivada, Krishna, & Rallan, 2016; Ramirez & Lammer, 2004; Rohmann et al, 2006; Roodhooft, Brussaard, Elst, & Van Acker, 1990; Seymen et al, 2017; Shiang & Holmes, 1977; Talebi, Mardasi, Asl, Bavarsad, & Tizno, 2017; Thompson, Pembrey, & Graham, 1985). LADD syndrome may be genetically diagnosed, as it is known to be caused by mutations in FGFR2 , FGFR3 , and FGF10 (Rohmann et al, 2006; Shams et al, 2007).…”

“…| 9 of 11 RYU et al Levy, 1967;Mathrawala & Hegde, 2011;McKenna, Burke, & Mellan, 2009;Meuschel-Wehner, Klingebiel, & Werbs, 2002;Milunsky, Zhao, Maher, Colby, & Everman, 2006;Moses, 2013;Ostuni et al, 1995;Pathivada, Krishna, & Rallan, 2016;Ramirez & Lammer, 2004;Rohmann et al, 2006;Roodhooft, Brussaard, Elst, & Van Acker, 1990;Seymen et al, 2017;Shiang & Holmes, 1977;Talebi, Mardasi, Asl, Bavarsad, & Tizno, 2017;Thompson, Pembrey, & Graham, 1985). LADD syndrome may be genetically diagnosed, as it is known to be caused by mutations in FGFR2, FGFR3, and FGF10 (Rohmann et al, 2006;Shams et al, 2007).…”

Fgf10 is required for specification of non-sensory regions of the cochlear epithelium

“…In light of our findings that Fgf10 −/+ mice have posterior semicircular canal defects, it would be interesting to image the inner ears of LADD subjects with known FGF10 mutations to determine the status of the posterior semicircular canal. Interestingly, there is a case report of a LADD syndrome subject with unilateral dysplastic posterior and lateral semicircular canals (Moses, 2013), and another with bilateral dysplasia of the semicircular canals (Azar et al, 2000), but no information about the responsible mutations is available. Given that only one semicircular canal is affected in mice, it is likely that the remainder of the vestibular system compensates, though it is possible that an abnormal vestibular phenotype might be revealed with specific testing.…”

“…Nevertheless, imaging of some of these individuals has revealed cochlear hypoplasia (Lemmerling et al, 1999; Meuschel-Wehner et al, 2002; Moses, 2013). We did not detect any morphologic or molecular aberrations in the cochlear ducts of Fgf10 heterozygotes and their hearing is normal (Mansour et al, 2013), but homozygotes had cochlear defects that would be expected to cause hearing loss if the other major consequences of Fgf10 homozygosity, such as the failure of lung development, could be bypassed.…”