PEDIATRICS Pierre Robin Syndrome

NISHAD PATIL*, SUNIL MHASKE†, RAMESH B KOTHARI‡, SANDIP DEOKATE*, RAM SETHI*, PAVAN SURYAWANSHI*, RAHUL MASKI*, NIVRUTTI MUNDHE*, SURAJ NAIR#

ABSTRACT Pierre Robin syndrome (or sequence) is a condition present at birth, in which the infant has a smaller-than-normal lower jaw, a tongue that falls back in the throat, and has difficulty in breathing. Most infants, but not all, will also have a cleft palate, but none will have a cleft lip. This heterogeneous birth defect has prevalence of approximately 1 per 8,500 live births. The male- to-female ratio is 1:1, except in the X-linked form. Autosomal recessive inheritance is possible. Keywords: Cleft soft palate, micrognathia, obstructive sleep apnea, otitis media

ierre Robin sequence or complex is the name with good cry and weight at birth. The other siblings given to a birth condition that involves the lower (includes two males and two females) were not having Pjaw which is either small in size (micrognathia) or any congenital anomaly. On examination, her weight set back from the upper jaw (retrognathia). As a result, was 5.27 kg, length 61 cm, head circumference 39 cm the tongue tends to be displaced back towards the (normal - 44 cm) and chest circumference 38 cm. All throat, where it can fall back and obstruct the airway vital parameters were within normal limits as per her (glossoptosis). Most infants, but not all, will also have age. On head to toe examination, she was having high a cleft palate, but none will have a cleft lip. arched, U-shaped, cleft soft palate. Jaw was very small CASE REPORT with small receding chin (Figs. 1 and 2).

A 6-month-old female child was brought to our out patient department (OPD) by mother with complaints of fever, cough and running nose since last 2 days. Fever was of gradual onset, slowly rising, intermittent, moderate grade without any chills or rigors. Cough was also of gradual onset, dry, intermittent, without any diurnal or postural variations. Parents gave history of repeated attacks of upper respiratory tract infections, associated with a single episode of otitis media in the past. Also parents gave history of disturbed sleep pattern of baby. She was fifth issue of nonconsanguineous Figure 1. Pierre Robin syndrome. marriage, born as a full-term, normal, hospital delivery

*Resident †Professor and Head ‡Assistant Professor #Intern Dept. of Pediatrics, Padmashree Dr Vithalrao Vikhe Patil Medical College and Hospital Ahmednagar, Gujarat Address for correspondence Dr Sunil Mhaske Professor and Head, Dept. of Pediatrics Micrognathia Cleft palate Padmashree Dr Vithalrao Vikhe Patil Medical College and Hospital Near Govt. Milk Dairy, Vilad Ghat, Ahmednagar - 414 111, Gujarat Figure 2. Pierre Robin syndrome.

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Also jaw was far back in throat and the tongue was The alveolar overjet is the distance between the most large compared to the jaw. There was a small opening anterior points of the upper and lower alveolar arches. in the roof of mouth, that caused choking. She was The maxillary arch is the measurement between the having congenital talipes equino varus (CTEV) of right 2 tragi via the subnasal point and the mandibular foot. Presently, there was no earache or ear discharge. arch is the distance from the right to the left tragus The systemic examination was not showing any passing through the pogonion. Glossoptosis is noted in abnormality. An opinion from ENT specialist was also 70-85% of reported cases. Macroglossia and taken to examine middle and inner ear, which stated no ankyloglossia are relatively rare findings. The active otitis media as well as any hearing loss. combination of micrognathia and glossoptosis may cause severe respiratory and feeding difficulty in the DISCUSSION newborn. Obstructive sleep apnea may also occur. It can Lannelongue and Menard first described Pierre affect the soft and hard palate and is usually U-shaped Robin syndrome in 1891 in a report on 2 patients or V-shaped (Fig. 5). Occasionally, it may present as a with micrognathia, cleft palate and retro-glossoptosis. bifid or double uvula or as an occult submucous cleft. In 1926, Pierre Robin published the case of an infant The most common otic anomaly is otitis media, with the complete syndrome. Until 1974, the triad followed by auricular anomalies. Hearing loss is mostly was known as “Pierre Robin syndrome”; however, conductive, while external auditory canal atresia occurs the term “syndrome” is now reserved for those errors in only 5% of patients. Temporal bone computerized of morphogenesis with the simultaneous presence of planigraphs demonstrate inadequate pneumatization multiple anomalies caused by a single etiology. of the mastoid cavities in many patients with Pierre The term “sequence” has been introduced to include Robin sequence. Nasal deformities are infrequent and any condition that includes a series of anomalies consist mostly of anomalies of the nasal root. Dental caused by a cascade of events initiated by a single malformation. Over the years, there have been several names given to the condition, including Pierre Robin syndrome, Pierre Robin triad. Based on the varying features and causes of the condition, either “Robin sequence” or “Robin complex” may be an appropriate description for a specific patient. Pierre Robin was a French physician who first reported the combination of small lower jaw, cleft palate and tongue displacement in 1923. This heterogeneous birth defect has prevalence of approximately 1 per 8,500 live births. The male- to-female ratio is 1:1, except in the X-linked form. Autosomal recessive inheritance is possible. An Figure 3. Pierre Robin syndrome. X-linked variant has been reported involving cardiac malformations and clubfeet.

Otolaryngologic Manifestations Micrognathia is reported in the majority of cases (91.7%) (Figs. 3 and 4). It is characterized by retraction of the inferior dental arch 10-12 mm behind the superior arch. The mandible has a small body, obtuse genial angle and a posteriorly located condyle. The growth of the mandible catches up during the first year; however, mandibular hypoplasia resolves and the child attains a normal profile by approximately age 5-6 years. The jaw index is defined as the alveolar overjet multiplied by the maxillary arch divided by the mandibular arch. This index can be used to objectify mandibular growth. Figure 4. Micrognathia.

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deletion 4q syndrome, rheumatoid arthropathy, hypochondroplasia, Moebius syndrome, and CHARGE association.

Pathogenesis Three pathophysiological theories exist to explain the occurrence of Pierre Robin sequence.

ÂÂ The mechanical theory: This theory is the most a b accepted. The initial event, mandibular hypoplasia, occurs between the 7th and 11th week of gestation. Figure 5. U-shaped cleft palate a( ); V-shaped cleft palate b( ). This keeps the tongue high in the oral cavity, causing a cleft in the palate by preventing the and philtral malformations occur in one third of cases. closure of the palatal shelves. This theory explains Laryngomalacia occurs in approximately 10-15% of the classic inverted U-shaped cleft and the absence patients with Pierre Robin sequence. Gastroesophageal of an associated cleft lip. Oligohydramnios could reflux and esophagitis has also been described. play a role in the etiology, since the lack of amniotic Speech defects occur frequently in patients with Pierre fluid could cause deformation of the chin and Robin sequence. Velopharyngeal insufficiency is usually subsequent impaction of the tongue between the more pronounced in these patients than in those with palatal shelves. isolated cleft palate. ÂÂ The neurological maturation theory: A delay in neurological maturation has been noted on Systemic Manifestations electromyography of the tongue musculature, the In general, systemic anomalies can be seen in various pharyngeal pillars and the palate, as has a delay cases. Anomalies involving the musculoskeletal system in hypoglossal nerve conduction. The spontaneous are the most frequent systemic anomalies. They correction of the majority of cases with age supports include syndactyly, dysplastic phalanges, polydactyly, this theory. clinodactyly, hyperextensible joints and oligodactyly ÂÂ The rhombencephalic dysneurulation theory: in the upper limbs. In the lower extremities, foot In this theory, the motor and regulatory anomalies (clubfeet, metatarsus adductus), femoral organization of the rhombencephalus is related to malformations (coxa varus or valgus, short femur), hip a major problem of ontogenesis. anomalies (flexure contractures, congenital dislocation), anomalies of the knee (genu valgus, synchondrosis) Conservative Management and tibial abnormalities have been reported. Vertebral ÂÂ In the majority of patients, conservative column deformities include scoliosis, kyphosis, lordosis, management with close observation and follow- up vertebral dysplasia, sacral agenesis and coccygeal sinus. is successful. The natural history shows that with Cardiovascular findings such as benign murmurs, normal growth, airway compromise resolves pulmonary stenosis, patent ductus arteriosus, patent without immediate surgical intervention. Isolated foramen ovale, atrial septal defect and pulmonary Pierre Robin syndrome patients usually respond hypertension have all been documented. more favorably to the conservative approach. ÂÂ Recently, Abel et al (2012) reported on long- Central nervous system (CNS) defects such as language term outcomes in 104 children with Pierre Robin delay, epilepsy, neurodevelopmental delay, hypotonia syndrome and airway obstruction. In most children and hydrocephalus may occur. Ocular anomalies are (86.5%), airway obstruction was managed by seen as per following in decreasing order of frequency: conservative measures or with a nasopharyngeal hypermetropia, myopia, astigmatism, corneal sclerosis airway (NPA) for a few months. and nasolacrimal duct stenosis. Genitourinary defects ÂÂ Prone positional therapy has proved to be highly may include undescended testes, hydronephrosis and efficient in airway management. Oral airway hydrocele. placement, laryngeal mask, nasopharyngeal Associated syndromes and conditions include stenting and short-term intubation (<2 week) are Stickler syndrome, trisomy 11q syndrome, trisomy other options in case positioning is inadequate. 18 syndrome, velocardiofacial (Shprintzen) syndrome, Intubation is often difficult owing to the

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micrognathia and should be performed by lengthening by gradual distraction may be used someone specialized in problematic pediatric for severe mandibular hypoplasia that causes airway management. obstructive apnea. Published articles by Hong ÂÂ Feeding difficulties can be alleviated by upright and others (2011, 2012) on the use of mandibular feeding techniques, modification of the nipple for distraction osteogenesis in Pierre Robin syndrome bottle feeding, temporary use of nasogastric or patients have described significant improvements orogastric feeding tube and the placement of a in both airway obstructive symptoms and feeding gastrostomy. Palatal plates such as the pre-epiglottic abnormalities. Patients showed clinical and baton plate, which have a velar extension, pull the objective improvements in reflux and swallowing base of the tongue forward. This can be helpful function after surgery. in the relief of airway obstruction, and it also ÂÂ As the therapy of choice to correct the conductive facilitates the swallowing mechanism during feeds. hearing loss and prevent middle ear complications, tympanostomy tubes are usually inserted when the Surgical Management palatoplasty is performed.

ÂÂ Infants with pronounced micrognathia may ÂÂ Surgical procedures to repair the cleft palate, experience severe respiratory distress or failure details of which are not included herein, fall into to thrive. Treatment is prioritized according to the 1 of 2 categories. The first category comprises all severity of airway compromise followed by the the one-stage procedures, and the second includes extent of feeding difficulties. Lidsky et al (2008) all multistage approaches in which the velum is reviewed 67 Pierre Robin syndrome patients from initially closed and hard palate repair is delayed. their multidisciplinary cleft team at a tertiary The most common procedure is the single-stage pediatric hospital. They found that delaying airway palate (hard and soft) closure, performed when the intervention may necessitate feeding assistance child is aged 6-18 months. via a G-tube. Surgical intervention is necessary in these cases. BIBLIOGRAPHY

ÂÂ Although many different surgical procedures have 1. Abel F, Bajaj Y, Wyatt M, Wallis C. The successful use of been described, tracheostomy remains the most the nasopharyngeal airway in Pierre Robin sequence: an widely used technique. Other surgical procedures, 11-year experience. Arch Dis Child. 2012;97(4):331-4. such as subperiosteal release of the floor of the 2. Bath AP, Bull PD. Management of upper airway mouth (Fig. 6), and different types of glossopexy, obstruction in Pierre Robin sequence. J Laryngol Otol. 1997;111(12):1155-7. such as the Routledge procedure or other forms of tongue-lip adhesions, can be used. Any 3. Breugem CC, Courtemanche DJ. Robin sequence: clearing nosologic confusion. Cleft Palate Craniofac J. glossopexy should be released before significant 2010;47(2):197-200. dentition develops (age 9-12 months). Mandibular 4. Bronshtein M, Blazer S, Zalel Y, Zimmer EZ. Ultrasonographic diagnosis of glossoptosis in fetuses with Pierre Robin sequence in early and mid pregnancy. Am J Obstet Gynecol. 2005;193(4):1561-4. 5. Bütow KW, Hoogendijk CF, Zwahlen RA. Pierre Robin sequence: appearances and 25 years of experience with an innovative treatment protocol. J Pediatr Surg. 2009;44(11):2112-8. 6. Caouette-Laberge L, Plamondon C, Larocque Y. Subperiosteal release of the floor of the mouth in Pierre Robin sequence: experience with 12 cases. Cleft Palate Craniofac J. 1996;33(6):468-72. 7. Dionisopoulos T, Williams HB. Congenital Anomalies of the Ear, Nose and Throat. New York, NY: Oxford University Press; 1997. pp. 243-60. Figure 6. Diagram illustrating the surgical technique for 8. Elliott MA, Studen-Pavlovich DA, Ranalli DN. Prevalence subperiosteal release of the floor of mouth in patients with of selected pediatric conditions in children with Pierre Pierre Robin sequence. Robin sequence. Pediatr Dent. 1995;17(2):106-11.

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9. Evans AK, Rahbar R, Rogers GF, Mulliken JB, Volk 16. Marques IL, Barbieri MA, Bettiol H. Etiopathogenesis MS. Robin sequence: a retrospective review of 115 of isolated Robin sequence. Cleft Palate Craniofac J. patients. Int J Pediatr Otorhinolaryngol. 2006;70(6): 1998;35(6):517-25. 973-80. 17. Morovic CG, Monasterio L. Distraction osteogenesis for 10. Haapanen ML, Laitinen S, Paaso M, Ranta R. Quality of obstructive apneas in patients with congenital craniofacial speech correlated to craniofacial characteristics of cleft malformations. Plast Reconstr Surg. 2000;105(7): palate patients with the Pierre Robin sequence. Folia 2324-30. Phoniatr Logop. 1996;48(5):215-22. 18. Myer CM 3rd, Reed JM, Cotton RT, Willging JP, Shott SR. Airway management in Pierre Robin sequence. 11. Handzic-Cuk J, Cuk V, Gluhinic M. Mastoid Otolaryngol Head Neck Surg. 1998;118(5):630-5. pneumatization and aging in children with Pierre-Robin syndrome and in the cleft palate population out of 19. Pasyayan HM, Lewis MB. Clinical experience with the syndrome. Eur Arch Otorhinolaryngol. 1999;256(1):5-9. Robin sequence. Cleft Palate J. 1984;21(4):270-6. 12. Hong P, Brake MK, Cavanagh JP, Bezuhly M, Magit 20. Sheffield LJ, Reiss JA, Strohm K, Gilding M. A genetic AE. Feeding and mandibular distraction osteogenesis follow-up study of 64 patients with the Pierre Robin complex. Am J Med Genet. 1987;28(1):25-36. in children with Pierre Robin sequence: a case series of functional outcomes. Int J Pediatr Otorhinolaryngol. 21. Syndromes with oral manifestation (Chap 308). In: 2012;76(3):414-8. Kliegman RM, Behrman RE, Jenson HB, Stanton BF (Eds.). Nelson Textbook of Pediatrics. 18th Edition Philadelphia, 13. Hong P. A clinical narrative review of mandibular Pa: Saunders Elsevier; 2007. distraction osteogenesis in neonates with Pierre Robin sequence. Int J Pediatr Otorhinolaryngol. 2011;75(8):985-91. 22. Tewfik TL, Teebi AS, Der Kaloustian VM. Selected syndromes and conditions. In: Tewfik TL, Der Kaloustian 14. Lehman JA, Fishman JR, Neiman GS. Treatment of cleft VM (Eds.). Congenital Anomalies of the Ear, Nose and palate associated with Robin sequence: appraisal of risk Throat. New York, NY: Oxford University Press; 1997. pp. factors. Cleft Palate Craniofac J. 1995;32(1):25-9. 516-7. 15. Lidsky ME, Lander TA, Sidman JD. Resolving feeding 23. Vegter F, Hage JJ, Mulder JW. Pierre Robin syndrome: difficulties with early airway intervention in Pierre Robin mandibular growth during the first year of life. Ann Plast Sequence. Laryngoscope. 2008;118(1):120-3. Surg. 1999;42(2):154-7. ■ ■ ■ ■

Revised Beighton Score to Assess Joint Hypermobility in Preschool Children In a new study, the revised Beighton score was applied to preschool children to evaluate joint hypermobility in five parts of the body. In all, 284 healthy preschool children (146 boys and 138 girls) and 26 preschool children with genetic disorders (15 boys and 11 girls) were assessed. A cut-off score >4 was used to identify hypermobility. About 7% healthy children and 89% with genetic syndromes associated with hypermobility had a score >4. The revised version of the Beighton score could help define generalized hypermobility for children up to 5 years of age. The findings are published online June 20 in the Journal of Pediatrics.

Vitamin D Supplementation in Very Low Birth Weight Preterm Neonates Vitamin D supplementation in a dose of 1,000 IU/day is more effective in maintaining serum calcium, phosphate, alkaline phosphatase (ALP), 25(OH)D and parathormone levels with lower incidence of skeletal hypomineralization and better growth among very low birth weight preterm neonates, suggests a newstudy published online June 19 in the Journal of Tropical Pediatrics. After 6 weeks of supplementation, the mean serum calcium and 25(OH)D levels were significantly higher and ALP and parathormone levels significantly lower in neonates receiving 1,000 IU/day vitamin D.

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