Pierre Robin Syndrome (PRS) – Patient Information/ Management

Overview

Pierre Robin Syndrome (PRS) is a relatively common pediatric congenital abnormality seen in clinical practice. It is characterized by the presence of Micrognathia, cleft palate and airway obstruction which forms the triad of Pierre Robin Syndrome. Children suffering from this condition have a normal size tongue but with a poorly developed (hypoplastic) mandible and a malformed floor of the mouth. Due to the tongue and mouth mismatch, airway obstruction occurs. Airway obstruction is usually relieved with the patient placed in a prone position for the tongue to fall forward hence preventing airway obstruction. It is actually a sequence in which the initial defect leads to the formation of subsequent malformations. This disorder was first described by Pierre Robin in 1923 [1].

Etiology

Till date, the exact cause of Pierre Robin Syndrome is unknown. Clinicians and medical researchers consider it to be an Autosomal recessive disorder. A subtype of this syndrome is thought to be an X-linked disorder. However, gene map performed revealed that GAD67 found on 2q31, SOX gene on 17q24.3-q25 and PVRL1 on 11q23-q24 are important genes associated with PRS [2].

Epidemiology

Pierre Robin Sequence is a rare congenital abnormality usually seen in associated with other congenital genetic defects. In a retrospective study carried out in Denmark with the aim of studying the epidemiology of PRS, 50 children (25 boys and 25 girls) were found to have the disorder from 1990-1999. This gave an incidence rate of 1:14,000 live births. 33 of the children had the classical U shaped cleft palate, 19 had several other associated syndromes while 17 had varying types of intrauterine impairment [3].

In Germany, another epidemiological study conducted from August 2011 to July 2012 showed a total number of 82 cases of PRS. This gave an incidence rate of 12.4 per 100,000 live births in Germany [4].

Pathophysiology

Different theories have been postulated as the possible pathophysiology for this syndrome. However, the most accepted theory is the mechanical theory. In the mechanical theory, a defect in mandibular development occurs around the 7th and 11th weeks of intrauterine gestation causing poor mandibular hypoplasia. When this occurs, the tongue is pushed high up within the oral cavity with subsequent development of cleft palate from the failure of palatal shelves closure from the high tongue. This is the widely accepted pathophysiology [1]. Other theories are the rhombencephalic dysneurualtion theory which describes defects in ontogenesis of the regulatory and motor organization of the rhombencephalus and the neurological maturation theory which describes the delay in neurologic maturation of the hypoglossal nerve which supplies the tongue, palate and the pillars of pharynx. This delayed contributes to the hypoplastic mandible seen in Pierre Robin Sequence.

Presentation

The clinical presentation/ symptoms of Pierre Robin Syndrome are divided into two distinct groups in relationship to the affected organ. Symptoms are divided into otolaryngologic and system manifestations. In a retrospective carried out in 55 children with this syndrome, 9.1% had associated syndromes, 36.4% developed respiratory distress, 90.9% had recurrent otitis media, and 54.5% had associated feeding difficulties [5].

Otolaryngologic symptoms

Otolaryngologic symptoms are symptoms related to the ear, throat and nose. Of all the otolaryngologic symptoms, micrognathia (small jaw bone) is the commonest symptom. It is seen in about 92% of children presenting with Pierre Robin Syndrome. The second commonest symptom is glossoptosis which is seen in about 70-85% of these children. Problems seen in children with PRS are related to difficulty in feeding during the neonatal period from the poorly developed jaw bone and from the tongue falling backwards. This results in difficulty in breathing and respiratory obstruction.

Obstruction sleep apnea has also been reported in patients with PRS and this occurs due to wrong positioning during sleep. Due to the malformation of the mouth, nose, ear and throat, children with PRS have an increase susceptibility to ear infection from recurrent bacterial infection which may damage the ear drums. Associated congenital abnormalities of the ear in these patients may cause hearing impairment and deafness.

Systemic symptoms

Systemic symptoms are symptoms of PRS that affect different organs of the body. This manifestation occurs alongside the triad of Pierre Robin Syndrome. Musculoskeletal symptoms are the commonest systemic symptoms seen in patients with PRS. This affects the muscles and bones leading to malformations like club feet, coxa varus or coxa valgus, genu varus, scoliosis, kyphosis, lordosis, sacral agenesis and coccygeal sinus [6]. Symptoms like shortsightedness, long sightedness, astigmatism, color blindness, blurring of vision and corneal scarring are eye symptoms seen in patient with PRS. The heart is also not spared in PRS, congenital heart disorders are relatively common accounting for heart failures and early death in these children. Defects in the artrioventricular septum, atrial septal defect and patent foramen ovale are commonly seen.

Disturbances of the brain and the central nervous system lead to hydrocephalus, seizure disorders and epilepsy and delay in achieving development mile stones. The kidneys and urinary tract is also involved presenting with hydronephrosis, undescended testes and hydrocele.

Workup (Diagnosis)

Workup for PRS includes radiographs of the jaw bone and other bone radiographs to check for mandibular hypoplasia and other congenital abnormalities. Diagnosis of PRS is made based on clinical features and genetics. Full genetic evaluation is essential in all patients with symptoms suggestive of PRS. FISH for deletions in chromosome 22q, mutations in TCOF1 gene are also appropriate genetic studies. Other workup includes the assessment of the airway, endoscopy of the airway helps to identify the site and cause of the obstruction [7].

Management and Treatment

Conservative management includes the use of nasopharyngeal airway to prevent airway obstruction, upright feeding posture, and special nipple for feeding with a feeding bottle, use of nasogastric or orogastric feeding tubes for short term usage, pulling of the tongue forward with the aid of special devices. In the treatment of children with PRS, a multidisciplinary approach should be adopted. A team of neonatologist and pediatricians, ENT surgeons, plastic and reconstructive surgeons, dentist, orthodontist, audiologist, specialist nurses, social welfare and child support groups should be incorporated into the treatment of such children.

Aim of treatment is to secure airway to prevent respiratory distress, improve feeding and to prevent hearing loss. Airway can be maintained using glossopexy in which the tongue is tied to the upper lip to preventing it from falling backwards, distraction osteogenesis which involves gradual elongation of the mandibular bone [8]. In a retrospective study in a hospital from 1981-1998, 74 patients with PRS were found. Tracheostomy was performed in 5 patients, feeding problems was found in 25% while 52 patients were treated conservatively with prone/ lateral positioning and close observation [9]. Pharyngeal tube can also be used effectively in the management of airway obstruction caused by PRS [7].

Prognosis

With adequate care and treatment, children with PRS can grow to become active adults with normal mental development. This can only occur if airway obstruction and feeding problems are addressed early in life. Chronic and recurrent airway obstruction during the developmental age can affect neurological development by causing brain cell damage and mental sub-normality. Poor feeding from cleft palate can cause chronic malnutrition, failure to thrive and stunted growth.

It is important that children with PRS are followed up closely as they grow for early detection of other medical problems associated with this syndrome [10].

Patient Information

Pierre Robin Syndrome is a rare congenital abnormalities characterized by poor development of the jaw bone, cleft palate and airway obstruction caused by the relatively large tongue (in relation to the narrow mouth). In children with PRS, airway obstruction is a life threatening complication. Other problems associated with PRS are poor feeding from cleft palate and the large tongue which can lead to poor growth, hearing problems and poor development are also important problems facing this children. PRS as a disorder rarely occurs alone, it frequent occurs in association with other congenital abnormalities especially Sticklers syndrome.

Children with PRS need proper care especially care to prevent airway obstruction and to improve on feeding. They are usually nursed in the prone position to prevent the tongue from falling back. Special devices like special nipples, pacifiers are used to ensure proper feeding. Some physicians may recommend the use of cup and spoon for feeding. With proper care, most children with this syndrome grow to live normal adult life. However, they are prone to complications including recurrent ear infection.

References

1. Gangopadhyay N, Mendonca DA, Woo AS. Pierre Robin Sequence. Seminars in Plastic Surgery. 2012;26(2):76-82.
2. Jakobsen LP, Knudsen MA, Lespinasse J, et al. The genetic basis of the Pierre Robin Sequence. The Cleft palate-craniofacial journal. 2006;43(2):155-159.
3. Printzlau A, Andersen M. Pierre Robin sequence in Denmark: a retrospective population-based epidemiological study. The Cleft palate-craniofacial Journal. 2004;41(1):47-52.
4. Vatlach S, Maas C, Poets CF. Birth prevalence and initial treatment of Robin sequence in Germany: a prospective epidemiologic study. Orphanet journal of rare diseases. 2014;9(1):9.
5. Elliott M, Studen-Pavlovich D, Ranalli D. Prevalence of selected pediatric conditions in children with Pierre Robin sequence. Pediatric dentistry. 1994;17(2):106-111.
6. Tomaski SM, Zalzal GH, Saal HM. Airway obstruction in the Pierre Robin sequence. The Laryngoscope. 1995;105(2):111-114.
7. de Buys Roessingh AS, Herzog G, Hohlfeld J. Respiratory distress in Pierre Robin: successful use of pharyngeal tube. Journal of Pediatric Surgery. 9// 2007;42(9):1495-1499.
8. Huang F, Lo L-J, Chen Y-R, Yang JC, Niu C, Chung M. Tongue-lip adhesion in the management of Pierre Robin sequence with airway obstruction: technique and outcome. Chang Gung Med J. 2005;28(2):90-96.
9. Van den Elzen AP, Semmekrot BA, Bongers EM, Huygen PL, Marres HA. Diagnosis and treatment of the Pierre Robin sequence: results of a retrospective clinical study and review of the literature. European journal of pediatrics. 2001;160(1):47-53.
10. Smith JL, Stowe FR. The Pierre Robin syndrome (Glossoptosis, Micrognathia, Cleft palate) A review of 39 cases with emphasis on associated ocular lesions. Pediatrics. 1961;27(1):128-133.