Crouzon Syndrome was first described by French physician Octave Crouzon in 1912 who noted the features in a mother and daughter. It is one of the craniosynostosis syndromes that result from a mutation of the fibroblast growth factor receptor gene. It is classically associated with bicoronal synostosis, midface hypoplasia, proptosis, and normal intellect.

Crouzon Syndrome is a rare disease, affecting only approximately 1.6 in every 100,000 births [1].

Crouzon syndrome is a genetic syndrome with autosomal dominant inheritance and typically complete penetrance. The majority of cases are associated with various mutations of the FGFR2 genes although one variant, Crouzon with acanthosis nigricans is associated with mutations of the FGFR3 gene [1]. Typically these are missense mutations [1].

Patients with Crouzon’s typically present at birth with classic phenotypic abnormalities that should raise the clinician’s suspicions for one of the craniosynostosis disorders. These findings include craniosynostosis (i.e., bilateral coronal suture synostosis, pansynostosis, or clover leaf skull), hypertelorism, beaked nose and midface hypoplasia. There may also be limb involvement, however, the absence of syndactyly and broad thumbs can help differentiate the syndrome clinically from others such as Pfeiffer and Apert’s (see below). Also, unlike patients with Pfeiffer and Apert’s, patients with Crouzon’s do not typically have neurocognitive impairment. Due to the presence of craniosynostosis, these patients are at high risk for development of increased intracranial pressure and should be monitored closely for signs of such.

The diagnosis of Crouzon’s is typically suspected based on clinical findings as noted above, however, ultimately diagnosis typically requires molecular testing and identification of mutations within the FGFR2 gene.

As with all patients with midface disorders, the first step in management of these patients is the establishment of a stable airway. Midface retrusion, choanal atresia, nasopharyngeal narrowing, and tracheal/laryngeal abnormalities may all contribute to airway obstruction. Stabilization may require nasopharyngeal airway placement, intubation, and/or tracheotomy. Shallow orbits and severe proptosis require aggressive management to prevent exposure keratitis and ulcerations. Temporizing tarsorrhaphies may ultimately be required until midface reconstruction can be completed.

In patients with elevated intracranial pressures, decompression procedures are warranted on an urgent basis. Of the craniosynostosis disorders, Crouzon’s has the highest risk of significant intracranial hypertension [1]. However, in the absence of these findings, cranial vault expansion has traditionally been delayed until around 6–12 months of age [2]. With the advent of endoscopic approaches however, the age to intervene is trending toward a younger age with some institutions performing elective strip craniectomies as early as 3 months [3]. Midface procedures are typically delayed until around 5 years of age [4]. Due to the underlying biology of these syndromes, high rates of reoperation have been reported [4].

As with patients with other craniosynostosis syndromes, children with Crouzon’s are typically best served at large medical institutions with multidisciplinary craniofacial teams that include pediatricians, otolaryngologists, oral maxillofacial surgeons, geneticists, and others. All patients should also be evaluated with developmental screens and management as indicated.

Eugene Apert, a French pediatrician, first described nine people in 1906 with the similar findings of craniosynostosis, midface hypoplasia, and syndactyly of hands and feet [5, 6]. Most cases (>98 %) are due to the mutation of chromosome bands 10q25–q26 [7].

The prevalence of Apert Syndrome is roughly 1 in 65,000 newborns. It is the cause of 4.5 % of cases of craniosynostosis and is equally distributed between male and females [8].

Apert syndrome is most commonly caused by a missense substitution mutation in chromosome bands 10q25–q26. The mutation affects downstream production of adjacent amino acids (i.e., Ser252Trp, Ser252Phe, Pro253Arg) in the linker between the second and third extracellular immunoglobulin domains of fibroblast growth factor receptor 2 (FGFR2). The inheritance pattern is thought to be autosomal dominant [6].

The typical findings of Apert syndrome are those of craniosynostosis (coronal, sagittal, metopic), midface hypoplasia, and syndactyly of the hands and/or feet. The skull appearance is a flat elongated forehead with bitemporal widening and occipital flattening. The skull may appear like a “cloverleaf” depending on the position of the temporal bones. The midface is hypoplastic with a flat nose and bulbous tip. The palate is arched with swelling of the palatine processes creating a “pseudocleft” in the midline. Soft palate clefting is found in 30 % of cases. Dentition tends to be crowded with an anterior open bite. Hand anomalies consist of variable syndactyly of the second through fourth fingers, ranging from webbing to complete fusion. Equal variability is seen between the second and fourth digits of the feet. The combination may be referred to as “mitten hand” and “sock foot” [8, 9].

The majority of cases are diagnosed based on physical exam findings in keeping with Apert Syndrome. Imaging in the form of plain films and computed tomography will be required for diagnostic and therapeutic purposes. Genetic evaluation may be performed to confirm the diagnosis [8, 9].

Each of the three typical components of Apert Syndrome will typically require surgical intervention. Craniotomy will be required in the first year of life for associated craniosynostoses: coronal, sagittal, and/or metopic. Syndactyly repair will be carried out soon thereafter for functional gain. Midface and frontoorbital advancement is typically performed later for cosmetic improvement while orthodontic treatment will be carried out as soon as possible to improve teeth alignment [8, 9].

Given the cranial and extracranial manifestations of Apert syndrome, multidisciplinary care of patients is required. Ideally, in a collaborative center, surgical intervention will be staged based on functional and cosmetic goals.

Pfeiffer syndrome was first described in 1964 as a rare craniosynostosis syndrome associated with craniosynostosis, midface hypoplasia, broad thumbs, great toes, and variable syndactyly of the hands and feet [10]. It is caused by mutations in the fibroblast growth factor genes [10–13]. These mutations can be transmitted in an autosomal dominant fashion or arise de novo. Interestingly, the spontaneous mutation is thought to be related to advanced paternal age [13].

Pfeiffer syndrome affects an estimated one in 100,000 live births [14]. Men and women are affected equally [15].

Pfeiffer syndrome is associated with more than 25 mutations on one of the two FGFR genes. Five percent of the patients have a mutation on FGFR1. These individuals are likely to present with the less severe phenotype (Type 1). The majority of patients, however, present with a mutation on the FGFR2 gene (Type 2 and 3).

Abnormal development of structures derived from preformed cartilage appears to be at the root of many of the abnormalities seen with Pfeiffer’s Syndrome [15]. These structures, which include the skull, trachea, spine, fingers, and ribs can be affected to various degrees depending on the severity of the phenotype. Type 1 “classic” Pfeiffer syndrome involves mild manifestations including brachycephaly, midface hypoplasia, and short, broad thumbs and great toes. These individuals generally have normal intelligence and good long-term prognosis. Type 2 Pfeiffer syndrome is generally associated with the classic “cloverleaf skull,” extreme proptosis, finger and toe abnormalities, elbow ankylosis or synostosis, developmental delay and neurological complications. Type 3 is similar to type 2 but without a cloverleaf skull. Infants born with any craniofacial dysostosis may have moderate to severe midface hypoplasia. This may significantly narrow the nasal and nasopharyngeal airway potentially causing severe airway obstruction.

The majority of cases of Pfeiffer syndrome are diagnosed clinically based on classic phenotypic findings to include craniosynostosis with a wide head and flat occiput, midface hypoplasia, ocular proptosis, short broad thumbs and great toes with deviation away from other digits, various degrees of syndactyly [16]. Molecular diagnosis may also play a role particularly in suspected, but not classic cases of Pfeiffer’s. Rarely, prenatal diagnosis is possible via ultrasound. Ultrasound findings of craniosynostosis and broad thumbs and toes should raise a suspicion for Pfeiffer syndrome.

Infants are obligate nasal breathers and therefore any condition affecting the midface can potentially affect their airway. Airway management is therefore a cornerstone of treatment for all neonates born with midface disorders. For infants with severe obstruction, nasopharyngeal airway placement or intubation may be necessary. Ultimately many of these children will require tracheostomy tube placement. Once the patient’s airway is secure, long-term plans for reconstructive surgery can be made. Temporizing procedures such as tarsorrhaphy are often necessary due to the severe proptosis which may inhibit complete eye closure. Ultimately the synostotic sutures require release in order to decompress the brain. This procedure may take place as early as 3 months of age [16]. Subsequent surgeries typically include midface distraction osteogenesis to both improve airway dimensions as well as orbital volumes. These procedures may involve external or internal devices depending largely on the patient’s age and surgeon preferences [17].

The complexity of these patients mandates that a multidisciplinary approach be taken to their long-term management. These children are typically best served at large medical institutions with multidisciplinary craniofacial teams that include pediatricians, otolaryngologists, oral maxillofacial surgeons, geneticists, and others.

Rhinitis of infancy is a clinical entity that is seen commonly in pediatric otolaryngology practice; however, a paucity of literature exists regarding this problem. The condition is the most common cause of neonatal nasal obstruction. The etiology is unclear although there appears to be a seasonal component with most cases presenting in the fall or winter months [25].

Presenting signs can include stertor, mucoid nasal discharge, mucosal edema, difficulty feeding and intermittent apneas. Thought to be an under-recognized problem [25], it has even been implicated in the sudden infant death syndrome [28].

There have been some questions as to whether there is an atopic component to rhinitis of infancy. Nearly 10 % of children will display symptoms of allergic rhinitis by 18 months and there seems to be an association with parental history of allergic rhinitis [24]. However, immunologic mechanisms seem unlikely to play a major role in the first weeks of life given the mechanism of allergy as it is currently understood.

Rarely, primary ciliary dyskinesia (PCD) can manifest as neonatal rhinitis causing respiratory distress [20]. Suspicion is raised when plain films demonstrate dextrocardia. Diagnosis is by electron microscopy studies demonstrating morphological abnormalities in cilia obtained by bronchial or nasal mucosal brush biopsies. Treatment aims at improving pulmonary toilet [20]

Nasal saline and bulb suctioning should be utilized to clear the mucoid discharge. For severe cases, a short course of topical decongestant such as 0.125 % neosynepherine alone or in combination with topical corticosteroids such as 0.1 % dexamethasone ophthalmic drops may be considered. Dexamethasone drops can be cadministered for up to 1 month and then tapered [25]. Rarely does this condition require further intervention and most infants will respond within 12 weeks [25].

Neonatal rhinitis can usually be managed by the primary care physician or otolaryngologist. When indicated, allergy/immunology consultation should be considered.

It has been recognized since as early as 1936 that the forces on the neonatal face encountered during the birth process may impact the morphology of the nose and face [18]. The incidence of nasal septal deviation in the newborn is described at between 1.25 and 25 % [26, 27]. Incidence may be related to intrauterine positioning of the fetus with a breech position being associated with the highest incidence [18].

Morphologically, neonatal septal deviation can take the form of anterior dislocation off of the maxillary crest or anterior/posterior septal deformity [21]. On occasion, neonatal nasal septal deviation can be so severe as to cause obstructive symptoms, with cases severe enough to present with apneas and cyanotic episodes while awake [21].

Closed reduction of the anterior septum can be performed in the first days of life with good results [21]. In severe cases, formal septoplasty can be performed on infants as young as 8 days [21]. This can be done through either a transnasal or sublabial approach, either directly or with endoscopic visualization [21, 22].

Neonatal septal deviation can usually be managed by the otolaryngologist. In cases of suspected trauma, additional consultations may be necessary.

Infantile hemangiomas (IH) are the most common vascular tumors of infancy and are known to present very early in life. One review article published in the NEJM in 1999 reported that in neonates with infantile hemangiomas 55 % are present at birth and the remainder develops within the first few weeks of life [31]. Older studies suggest an incidence as high as 10 %, [30] however, more recent reviews of the existing literature highlight the general lack of methodologically standardized studies and place the presumed incidence more towards 4–5 % [46].