Background
Cornelia de Lange syndrome (CdLS) is a rare genetic disease with a prevalence range from 1:10.000 to 1:40.000. An international consensus statement has defined cardinal features to define classic and non-classic CdLS [1]. The classic phenotype is characterized by distinctive facial features, intellectual disability, growth delay, hirsutism, and upper-limb reduction.
The diagnosis of CdLS is established in a proband with suggestive clinical features and/or by identification of pathogenic variant in NIPBL, RAD21, SMC3, BRD4, HDAC8 or SMC1A by molecular genetic testing [1, 2].
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Many authors described maxillofacial and otolaryngological involvement in CdLS [3].
Sensorineural hearing loss is described in 80% of children with CdLS, with 40% being profoundly affected [4]. Other otolaryngological diseases are obstructive sleep apnea, laryngomalacia and rhinosinusitis.
Nasal polyps (NP) in CdLS [5, 6] were previously reported in association with chronic rhinosinusitis (CRS), however data about NP prevalence, diagnosis, treatment and prognosis are lacking for this cohort of patients.
We describe the whole diagnostic and therapeutic workflow of (NP) in two pediatric patients with CdLS, follow up information are reported, too.
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Cases presentation
Case 1
This female patient come to our Center of Rare Diseases when she was 5. She was classified as a classic CdLS [1], NIPBL gene mutation confirmed the diagnosis.
She have had severe gastro esophageal reflux disease (GERD), surgical treatment (Nissen fundoplication) was required. She presented severe obstructive sleep apnea syndrome (OSAS) that was treated by Continuous Positive Airway Pressure (CPAP). She did not have a history of CRS or allergy.
When she was 12, parents reported persistent nasal obstruction and worsening of sleep disorder.
Endoscopy revealed a nasal polyp (Video 1, supplementary materials) in the middle meatus, protruding in the right nasal fossa with mild nasal obstruction (endoscopic Type III nasal polyposis according to Stammberger Clinical classification) [7]. The NP diagnosis was histological proved.
The patient underwent intranasal steroid therapy for 6 months, with sleep disturbance improvement. After 2 years, endoscopy revealed absence of nasal polyposis.
Case 2
This female patient was diagnosed in the first year of age with CdLS, classic form [1].
She developed severe intellectual disability and moderate GERD treated by proton pump inhibitor. Recurrent nasal obstruction was detected, and OSAS was diagnosed when she was 6, CPAP treatment was performed.
When she was 17, because of worsening of nasal obstruction symptoms, endoscopy was performed and revealed NP associated with CRS.
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Multiple unilateral polyps were found, one in the nasal fossa and a second one in the maxillary sinus, as confirmed by CT scan (Type II according to Stammberger classification), the patient was successfully treated by endoscopic surgery.
Endoscopic recurrence of NP occurred after one year, nasal steroid therapy lead to resolution, as confirmed by endoscopy.
Discussion and conclusion
CdLS is a rare genetic syndrome with a high involvement of maxillofacial manifestations. No specific treatment is available, but multidisciplinary approach can improve the quality of life of patients [8].
NP is a rare event in healthy children; it is usually bilateral, commonly associated with asthma [9]. Most studies about children with CRS shown a lower prevalence of NP when compared to adults because there are differences in the inflammatory response [10].
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NP was occasionally described in adolescents and adults with CdLS [5, 8], despite this, chronic nasal obstruction and sleep disturbance are commonly reported [3], we suppose that NP prevalence can be underestimate in this cohort of patients due to lack of compliance, intellectual disability and autism.
In our experience (case 1) NP can be diagnosed even in patients with CdLS without CRS. We hypothesized that in some CdLS patients NP could be the result of chronic inflammation due to GERD, craniofacial features, velar insufficiency and generalized hypothonia. A long-term acid exposure could justify an increase in the prevalence of airway chronic inflammation in CdLS compared to the general population, especially in pediatric age.
Our report confirm that nasal endoscopy is a safe and useful tool in the diagnosis, treatment and follow-up of NP, even in CdLS pediatric patients.
We want to increase the alert for the detection of NP in patients with CdLS since pediatric age. We recommend endoscopy in all patients with CdLS and symptoms of chronic nasal obstruction and/or OSAS. Multidisciplinary team (otolaryngology, maxillofacial surgeon, pediatrician with expertice in disability, neurologist) and sedation service could be useful in the management of CdLS patients with airway obstruction symptoms and sleep disturbance when severe intellectual disability, autism or psychiatric findings are present.
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Declarations
Ethics approval and consent to participate
Not required.
Consent for publication
Written informed consent was obtained from the patient for publication of this case report and accompanying images.
Competing interests
The authors declare that they have no competing interests.
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