Syndromic Craniosynostosis

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Key points

  • Syndromic craniosynostosis is rare, occurring in 1:30,000 to 1:100,000 live births.

  • Fibroblast growth factor receptor and tumor growth factor-β receptor mutations have been reported to be associated with many forms of syndromic craniosynostosis.

  • Intracranial hypertension, developmental delays, and strabismus are more frequent in syndromic forms of craniosynostosis than isolated synostosis.

  • Distraction osteogenesis is a useful adjunct in syndromic synostosis to increase intracranial volume and is

Evaluation and diagnosis of craniosynostosis

Detailed pregnancy history, birth history, family history, and medication or drug exposure in utero is crucial to document. Syndromic forms of synostosis are often inherited in an autosomal-dominant (AD) fashion, although spontaneous mutations frequently occur. A review of systems should note any presence of associated headaches, irritability, seizures, or neurodevelopmental or cognitive delays. A timeline of the duration and progression of head shape change is important because progressive

Craniofacial team

Syndromic craniosynostosis often involves multiple organ systems so an interdisciplinary team approach is now the standard of care for these complicated patients.5 This team can include a plastic surgeon, pediatric otolaryngologist or facial plastic surgeon trained in craniofacial surgery, a pediatric neurosurgeon, an oral-maxillofacial surgeon, a pediatric anesthesiologist and intensivist, a pedodontist, orthodontist, a prosthodontist, a pediatric ophthalmologist, a psychologist, a geneticist,

Distraction osteogenesis

Distraction osteogenesis (DO) can be used to advance the mandible, midface, orbits, and skull including lower level and higher level Le Fort osteotomies, PCD, or fronto-facial (Monobloc) advancements using either external or internal distractors (Fig. 3). Cranial distraction has been used to increase microcephalic skulls or provide added volume in the case of shunt-induced craniosynostosis. It has also been described for use across patent sutures and other more unconventional total cranial

Molecular genetics

A variety of mutations in transcription-derived growth factors, such as transmembrane fibroblast growth factor receptors (FGFR) 1, 2 and 3 and tumor growth factor-β receptors 1 and 2, are known to be involved in syndromic craniosynostosis (see Table 1).35, 36, 37, 38 In addition, connective tissue structural proteins, such as fibrillin-1 (FBN1) and TWIST, have also been implicated in association with syndromic craniosynostosis.

Defects in FGFR1 and FGFR2 have been linked to such syndromes as

Hearing Loss

Literature review reveals a large range (4%–92%) in the incidence of hearing loss associated with FGFR in patients with syndromic craniosynostoses, such as Muenke, Apert, Pfeiffer, Crouzon, Jackson-Weiss, and Crouzon with acanthosis nigricans.54 Most of the hearing loss is a conductive hearing loss, with the exception of Muenke syndrome, where most patients have a sensorineural hearing loss (SNHL), and Crouzon syndrome, where approximately 50% of patients have a pure or component of SNHL.54

Respiratory Difficulty

Craniofacial syndromes

Craniofacial anomalies associated with syndromes vary distinctly in clinical presentation. Knowledge of the most common syndromes is important to focus the examination and understand when consultations are needed. The syndromes in the next sections are discussed from most common to least (Fig. 8).

Summary

Syndromic craniosynostosis is rare with characteristic craniofacial deformities, carpal-pedal anomalies, and cognitive impairment. Genetic mutations are associated with many forms of syndromic craniosynostosis. An interdisciplinary team approach and careful physical examination and history documentation is essential. DO is useful to increase intracranial volume often before the age of 1 year. FOA to gain additional cranial and orbital volume is still the mainstay of surgery around 9 to

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    • Global Epidemiology of Craniosynostosis: A Systematic Review and Meta-Analysis

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      These findings confirm our clinical understanding of craniosynostosis: syndromic craniosynostosis represents a minority of total craniosynostosis. Approximately 8.8% of craniosynostosis cases were syndromic, consistent with previous estimates of the birth prevalence of forms of syndromic craniosynostosis.49,50 Alderman et al. reported the highest birth prevalence of nonsyndromic craniosynostosis, though this may have resulted from excess reporting of unconfirmed cases.42

    • Anterior fontanelle closure and diagnosis of non-syndromic craniosynostosis: a comparative study using computed tomography

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      This function has been attributed to the sutures of the skull, whose early fusion could lead to craniosynostosis (CS). CS is classified as either syndromic if associated with craniofacial syndromic conditions such as Crouzon and Apert syndrome and commonly presents with skull base restriction and midface hypoplasia (incidence: 1 in 30,000 live births) or non-syndromic if no such syndromes are identified (incidence: 1 in 2,000 live births).5-7 Although AF closure before six months of age has been considered rare in several reports and is an indication of abnormal conditions such as hyperthyroidism, aberrant cerebral development, microcephaly, and even CS, no strong evidence of the association between CS and early AF closure has been obtained thus far.

    • The outcome of targeted NGS screening in patients with syndromic forms of sagittal and pansynostosis - IL11RA is an emerging core-gene for pansynostosis

      2022, European Journal of Medical Genetics
      Citation Excerpt :

      Notably, recent studies have indicated an association between IL11RA and an autosomal recessive form of CS with a Crouzon-like phenotype and predominantly pansynostosis (Brischoux-Boucher et al., 2018; Keupp et al., 2013; Korakavi et al., 2019; Miller et al., 2017; Nieminen et al., 2011). Although isolated sagittal involvement is most frequent in nonsyndromic CS, there are rare syndromes such as Shprintzen-Goldberg with a recurrent pattern of sagittal synostosis (Al Kaissi et al., 2017; Garza and Khosla, 2012; Shah et al., 1996; Shprintzen and Goldberg, 1982; Stoll, 2002; Wang et al., 2016). The aim of the present study was to investigate the prevalence and spectrum of genetic alterations in patients with syndromic forms of sagittal and pansynostosis.

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