Pena-Shokeir syndrome is a rare, autosomal-recessive disorder that usually affects newborns. Its etiology is poorly understood. Pena-Shokeir syndrome is defined by camptodactyly, multiple ankyloses, pulmonary hypoplasia, and various facial anomalies. These manifestations are usually severe, and death generally occurs at birth or shortly thereafter. We describe a case of Pena-Shokeir syndrome in a 9-year-old girl of above-normal intelligence who presented with life-threatening airway distress. To the best of our knowledge, she is the oldest living individual with Pena-Shokeir syndrome, and the only such patient whose intelligence was not impaired. We discuss the acute management and subsequent care of this patient, who not only survived, but maintained excellent grades in school.
Thirty years have passed since Pena and Shokeir first described their eponymous syndrome. (1) Its signs include camptodactyly, multiple ankyloses, pulmonary hypoplasia, and facial anomalies, including micrognathia, ocular hypertelorism, low-set and malformed ears, and a depressed nasal tip. Since 1974, several authors have added to our knowledge of this syndrome by reporting involvement of the cardiovascular, pulmonary, genitourinary, endocrine, gastrointestinal, and central nervous systems. (2-13)
Most patients with this syndrome do not survive beyond the neonatal period and, until now, only 1 such patient had been reported to have survived beyond 12 months. (3) Severe pulmonary hypoplasia, which is present in 83% of reported cases, is often the fatal component of PenaShokeir syndrome as it results in stillbirth or death within the first month of life. (6,10)
In this article, we describe a rare case of Pena-Shokeir syndrome that was characterized by heretofore unreported features.
A 9-year-old girl who had been diagnosed with the phenotypic Pena-Shokeir syndrome at birth was found unresponsive at home by her mother and rushed to a hospital. The mother reported that the girl had appeared to be quite fatigued throughout the preceding 2 weeks, but that she was otherwise normal.
The girl's medical history was significant for reactive airway disease and restrictive lung disease secondary to pectus carinatum with severe kyphoscoliosis. The child had previously been hospitalized for severe, generalized varicella, laryngotracheobronchitis, multiple episodes of pneumonia, and complications of acute otitis media. Her surgical history was significant for a temporary tracheotomy at birth; she was decannulated following a cleft palatoplasty, lengthening of the tendo calcaneus, and an open reduction for congenital hip dislocation. The patient had also experienced two episodes of malignant hyperthermia following induction of general anesthesia. She had developed apnea on one occasion following the administration of chloral hydrate. The child was not taking any medications at the time of her presentation. Her parents denied any family history of consanguinity or birth defects.
Just prior to her arrival at the hospital, the patient had developed acute respiratory distress at home (etiology unknown) and became progressively obtunded. Upon admission to the emergency department, her initial evaluation was notable for acute respiratory failure and continuous unresponsiveness. Airway protection via mask ventilation was initiated, intravenous fluids were started, and a Foley catheter was placed. Chest x-ray revealed bilateral lung infiltrates. An arterial blood gas analysis revealed severely decompensated respiratory acidosis. The complete blood count indicated leukocytosis and neutrophilia. Ceftriaxone was initiated in response to suspected pneumonia. Later, several attempts to intubate her in the emergency department were unsuccessful, necessitating continuous mask ventilation during a transfer by air ambulance to the Iowa Methodist Medical Center in Des Moines.
Upon arrival, marginal bleeding was noted in the patient's oropharynx; this was believed to be attributable to the numerous intubation attempts. The child's neck was fixed in hyperextension to the left, which revealed a scar from a previous tracheotomy. Unresponsive and in respiratory failure, she was brought immediately to the operating room, where an emergency tracheotomy was successfully performed. The child was transferred to the pediatric intensive care unit for continued monitoring. After several weeks, she was able to return home and required only nightly tracheotomy ventilator support.
Six weeks later, the child again collapsed at home, and she was transported again to the Iowa Methodist Medical Center for respiratory and nutritional evaluation. Upon her arrival at the pediatric intensive care unit, a physical examination revealed that her tracheotomy tube was stable and in good position without granulation. The next day, direct laryngoscopy under general anesthesia showed a near-complete supraglottic and suprastomal collapse and a marked anterior displacement of the larynx. A mild suprastomal granuloma was also noted. No other masses or lesions were identified inferiorly in the trachea or in the right or left mainstem bronchi. A loose tooth in the maxillary arch was found incidentally, and it was removed to obviate the possibility of aspiration. Dietary analysis revealed that her nutritional status was poor, and further diagnostic studies were planned. Ventilator rate settings were increased, and the patient was subsequently discharged home in good condition. At this point, her parents refused a gastrostomy tube for feeding.
Six months later, the patient was rehospitalized because of continued difficulty maintaining adequate nutrition, and a feeding gastrostomy tube was placed. Following tube placement, she returned home and her oral intake (which remained poor) was supplemented by nightly parenteral feedings. With adequate caloric intake assured, she experienced no further problems. She continues to undergo multispeciality medical evaluations quarterly. Despite the severe motor limitations imposed by the Pena-Shokeir syndrome, she continues to attend school and maintains an A average.
Pena-Shokeir syndrome is an uncommon, autosomal-recessive genetic disorder. (2) Affecting an estimated 1 in 12,000 newborns, the syndrome often strikes the offspring of consanguineous relationships. (8) Of the 60 cases that have been previously reported in the literature, 32 were familial and 28 were sporadic. (12,13) No racial predilection has been noted.
The exact etiology of Pena-Shokeir syndrome is unknown, but several theories have been proposed to explain its characteristic morphology. Investigations conducted by Moessinger support the hypothesis that the Pena-Shokeir phenotype is the result of a fetal akinesia/hypokinesia deformation sequence. (14) This would suggest that the time of onset and the severity of the decrease in fetal movement, together with genetic and environmental inputs, may interact to produce the observed variations in both the severity of the syndrome at the time of presentation and in the combinations of the defining characteristics demonstrated. (9)
Prenatal diagnosis of Pena-Shokeir syndrome is difficult, and most cases are not recognized until birth. Chromosomal analysis of affected patients has consistently revealed a normal karyotype. (1,2) Pregnancies complicated by polyhydramnios and intrauterine growth retardation on ultrasound should alert clinicians to the possible presence of Pena-Shokeir syndrome. (8) The affected fetus may also demonstrate skeletal dysplasias, the defining facial features of the syndrome, and pulmonary hypoplasia visible on ultrasound. (11) No specific treatment is available for those affected by Pena-Shokeir syndrome.
In summary, the recent presentation of a 9-year-old girl with Pena-Shokeir syndrome whose intelligence was not impaired adds a new dimension to our understanding of a condition that is almost always fatal during the neonatal period. This case demonstrates the potential late effects of this syndrome, and it indicates that early mortality is not inevitable.
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(2.) Pena SD, Shokeir MH. Syndrome of camptodactyly, multiple ankyloses, facial anomalies and pulmonary hypoplasia--further delineation and evidence for autosomal recessive inheritance. Birth Defects Orig Artic Set 1976; 12:201-8.
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(8.) Shenker L, Reed K, Anderson C, et al. Syndrome of camptodactyly, ankyloses, facial anomalies, and pulmonary hypoplasia (Pena-Shokeir syndrome): Obstetric and ultrasound aspects. Am J Obstet Gynecol 1985;152:303-7.
(9.) Hall JG. Invited editorial comment: Analysis of Pena Shokeir phenotype. Am J Med Genet 1986;25:99-117.
(10.) Bisceglia M, Zelante L, Bosman C, et al. Pathologic features in two siblings with the Pena-Shokeir I syndrome. Eur J Pediatr 1987; 146: 283-7.
(11.) Persutte WH, Lenkc RR, Kurczynski TW, Brinker RA. Antenatal diagnosis of Pena-Shokeir syndrome (type I) with ultrasonography and magnetic resonance imaging. Obstet Gynecol 1988;72:472-5.
(12.) Gyr T, Katz M, Altermatt HJ, et al. Lethal Pena-Shokeir 1 syndrome in three male siblings. Arch Gynecol Obstet 1992;251:149-54.
(13.) Billings KR, Kerner MM, Padbury JF, Abemayor E. Laryngotracheal stenosis in a case of Pena-Shokeir syndrome. Am J Otolaryngol 1997;18:226-8.
(14.) Moessinger AC. Fetal akinesia deformation sequence: An animal model. Pediatrics 1983;72:857-63.
Dr. Boesen is an otolaryngologist in private practice in Des Moines, Iowa. Dr. French is with the Department of Radiology, St. Luke's Medical Center, Milwaukee.
Reprint requests: Peter V. Boesen, MD, 1000 73rd St., Suite 18, Des Moines, IA 50311. Phone: (515) 267-0691; fax: (515) 327-1214; e-mail: email@example.com
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