Tracheal Cartilaginous Sleeve in Syndromic Craniosynostosis

Pickrell, Brent B.; Meaike, Jesse D.; Canadas, Karina; Chandy, Binoy; Buchanan, Edward P.

doi:10.1097/scs.0000000000003489

Cited by 15 publications

(2 citation statements)

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“…Normal tracheal homeostasis depends on a suitable FGFR2 signaling pathway to promote asymmetric self-renewing division generating one basal cell and one luminal cell per basal cell division (Balasooriya et al, 2017). Tracheal cartilaginous sleeve (TCS), a rare life-threatening condition, has been found in some individuals affected by mutations in FGFR genes (Pickrell et al, 2017;Wenger et al, 2017). Notably, Wenger et al identified TCS in 100% of FGFR2 p.Try290Cys mutated children (Wenger et al, 2017), in addition to a previous report of TCS in a BSS case (Wenger et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Report of a Father With Congenital Bilateral Absence of the Vas Deferens Fathering a Child With Beare–Stevenson Syndrome

Ferreira

Dantas

2020

Front. Genet.

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Background: Apert, Pfeiffer, and Crouzon syndromes are autosomal dominant diseases characterized by craniosynostosis. They are paternal age effect disorders. The association between paternal age and Beare-Stevenson syndrome (BSS), a very rare and severe craniosynostosis, is uncertain. Gain-of-function mutations in FGFR2 become progressively enriched in testes as men age and were shown to cause these syndromes. Case report: Here, we describe a child affected with BSS, whose father was 36 years old and had congenital bilateral absence of the vas deferens (CBAVD). The child was heterozygous for the pathogenic FGFR2 variant c.1124A > G p.Tyr375Cys. By reviewing the literature, we found that BSS fathers are older than BSS mothers (mean age in years: 39 ± 10 vs 30 ± 6, p = 0.006). Male age greater than 34 years and CBAVD are both factors associated with poor spermogram parameters, which may represent an additional selective pressure to sperm carrying FGFR2 gain-of-function mutations. Conclusion: These findings are consistent with the hypothesis that BSS is a paternalorigin genetic disorder. Further experimental studies would be needed to confirm this hypothesis.

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Section: Discussionmentioning

confidence: 99%

Report of a Father With Congenital Bilateral Absence of the Vas Deferens Fathering a Child With Beare–Stevenson Syndrome

Ferreira

Dantas

2020

Front. Genet.

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“…1213e Airway abnormalities are also common (40 to 50 percent), including tracheal sleeve or fusion rings, which have been reported in 80 percent of syndromic patients with FGFR mutations in one study. 31 Otolaryngology involvement is particularly important, especially in the early period, as mortality and morbidity rates for syndromic craniosynostosis patients with tracheal sleeve can be particularly high, especially in combination with upper airway obstruction common in these patients. Early intervention, frequently with tracheostomy, is needed.…”

Section: Syndromic Synostosismentioning

confidence: 99%

Update in Management of Craniosynostosis

Xue

Buchanan

Hollier

2022

Plastic &Amp; Reconstructive Surgery

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raniosynostosis refers to skull deformities caused by premature fusion of one or more sutures (Fig. 1). The incidence is estimated to be one in 2500 births. 1,2 More than 80 percent are isolated or nonsyndromic. The suture affected has a gender predisposition, with sagittal synostosis being four times more common in boys, and unicoronal synostosis 1.5 times more common in girls. 1,2 The pathogenesis of premature fusion in craniosynostosis remains unclear. There have been many hypotheses over the years, including intrauterine constraint, 3-7 hypophosphatemia and rickets, 8,9 maternal smoking, 10,11 and excessive use of antacids during infancy. 12 None were strongly supported.With the development of better genetic sequence technologies, more and more mutations have been identified in individuals with congenital abnormalities, and craniosynostosis is no exception. Recently, isolated sagittal synostosis has been linked to a mutation in the BBS9 gene 13 and metopic synostosis to a mutation in the FREM1 gene, 14 but the clinical significance of these findings is unclear. Other genes identified include SMAD6, which account for 7 percent of nonsyndromic sagittal and metopic synostosis, and 10 percent of familial cases. 15 A recent study demonstrated that the SMAD6 mutation may lead to poorer neurocognitive outcome as well. 16 Several mutations have been identified for syndromic craniosynostosis. Of these, the most common are the fibroblast growth factor receptor genes (FGFR1, FGFR2, and FGFR3). FGFR is a group of 22 proteins that regulate proliferation, differentiation, and migration of cells that are essential for wound healing, angiogenesis, and limb development. There are several craniosynostosis syndromes linked to mutations in this group of genes. Mutation in FGFR2 is linked to Apert, Crouzon and Beare-Stevenson syndromes. Pfeiffer syndrome is linked to mutations in both FGFR1 and FGFR2 mutations. Muenke syndrome and Crouzon with acanthosis nigricans are linked to FGFR3 mutations. 17 Saethre-Chotzen syndrome is associated with more than 100 mutations in the TWIST1 gene, 18 which codes for a transcription factor that specifies and maintains cellular identity.

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Complex Airway Management in Patients with Tracheal Cartilaginous Sleeves

et al. 2021

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Objectives/Hypothesis A tracheal cartilaginous sleeve (TCS) is a rare anomaly characterized by anterior fusion of tracheal cartilages. TCS is associated with syndromic craniosynostoses including Apert, Crouzon and Pfeiffer syndromes and FGFR2, FGFR3, and TWIST1 variants. This study presents a 30‐year review of patients with syndromic craniosynostosis and TCS and describes diagnostic methods, genetic variants, surgical interventions, and long‐term outcomes. Study Design Retrospective, single‐institution review. Methods This review included patients with syndromic craniosynostosis and TCS treated at Seattle Children's Hospital from 1990 to 2020. Tracheostomy, genetic variants, and additional surgery were primary measures. Fisher's exact test compared need for tracheostomy in patients with proposed high‐risk (FGFR2 p.W290 or FGFR2 p.C342) versus low‐risk genetic variants. Results Thirty patients with TCS were identified. Average age at diagnosis was 12 months (range 2‐weeks to 7.9‐years; standard deviation 19.8 months). Syndromes included Pfeiffer (37%), Apert (37%), and Crouzon (26%). Severe obstructive sleep apnea was present in 76% of patients. Tracheostomy was performed in 17 patients (57%); five were successfully decannulated. Additional interventions included adenotonsillectomy (57%), nasal (20%), laryngeal (17%), and craniofacial skeletal surgery (87%). All patients with Pfeiffer syndrome and FGFR2 p.W290C variants and 83% of patients with FGFR2 p.C342 variants required tracheostomy, differing from other variants (P = .02, odds ratio 33, 95% confidence interval 1.56–697.96). One patient (3%) died. Conclusion TCS contributes to multilevel airway obstruction in patients with syndromic craniosynostosis. Genetic testing in patients with FGFR2‐related syndromic craniosynostoses may identify those at risk of TCS and facilitate early intervention. A better understanding of this patient population may foster individualized airway management strategies and improve outcomes. Level of Evidence 4 Laryngoscope, 132:215–221, 2022

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Tracheal Cartilaginous Sleeve in Syndromic Craniosynostosis

Cited by 15 publications

References 14 publications

Report of a Father With Congenital Bilateral Absence of the Vas Deferens Fathering a Child With Beare–Stevenson Syndrome

Report of a Father With Congenital Bilateral Absence of the Vas Deferens Fathering a Child With Beare–Stevenson Syndrome

Update in Management of Craniosynostosis

Complex Airway Management in Patients with Tracheal Cartilaginous Sleeves

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