Pfeiffer Syndrome Type 2 An Unusual Syndrome Presenting

  • Slides: 1
Download presentation
Pfeiffer Syndrome Type 2: An Unusual Syndrome Presenting in its Usual Way Hannah Grace

Pfeiffer Syndrome Type 2: An Unusual Syndrome Presenting in its Usual Way Hannah Grace Lee D. O. PGY 1 University of Texas at Houston, Department of Pediatrics Abstract Literature Review Pfeiffer Syndrome is a rare autosomal dominant disorder that consists of craniosynostosis, partial hand feet syndactyly, broad deviated thumbs and big toes that affects 1/120, 000 births (2, 3). There are 3 subtypes and the presentations within each subtype themselves are highly variable and thus the management differs for each patient. Here, we present a Hispanic female patient with Pfeiffer Syndrome type 2 and the management of her particular case. We also present a brief literature review along with a mode to differentiate Pfeiffer’s Syndrome from other craniosynostosis syndromes. This report will focus on Pfeiffer’s Syndrome type 2. Introduction Dr. Rudolf Pfeiffer first described the syndrome in 1964 as an acrocephalosyndactyly syndrome that consisted of bicoronal craniosynostosis, midfacial hypoplasia, wide thumbs and big toes, and partial syndactyly of hands and feet (4). There are 3 subtypes of this syndrome: • Type 1: brachycephaly, midface, finger and toe deformities, typically have good long-term outcome with normal intelligence • Type 2: clover-leaf shaped skull with neurological complications, severe proptosis, finger and toe deformities, elbow ankylosis, visceral anomalies, typically have poor prognosis with death within 2 years of age (2, 3, 5) • Type 3: Like type 2 but with no clover-leaf head The syndrome results from mutations in the fibroblast growth factor receptor genes (FGFR) 1 or 2. FGFR plays an important role in cell signaling and its response to the environment. A mutation can prolong the signaling which can lead to early maturation of bone cells and premature fusing of the skull, hands, and feet. According to the American Journal of Medical Genetics in 2013, the FGFR mutation also affects various processes in embryonic development such as formation of blood vessels and wound healing (3). Along with the classic picture with the deformities of the hands, head and extremities described above, hydrocephaly, ocular proptosis, and abnormal viscera could be seen as well (2). Slow development and early death is not unusual for types 2 and 3. In this study, we touch briefly on the management and outlook for a child with type 2. In a article by American Journal of Medical Genetics, three generations of a British family with mutation were studied. It was seen that all three generations, while the mutation for FGFR was present in each, had variable presentations. This illustrated autosomal dominant inheritance with complete penetrance is characteristic despite variable expressivity in Pfeiffer Syndrome (3, 4). Oyamada and colleagues have described congenital airway anomalies as playing a big part in morbidity and mortality in Pfeiffer Syndrome due to chronic hypoventilation and hypoxia (4). There has been speculation that sporadic cases of Pfeiffer Syndrome cases have been related to advanced paternal age as it was in the case of our patient and in a case by Bernstein in 2003 (5). In South Korea, a term baby was born to a healthy 40 year old G 3 P 3 mother. There was no family history genetic disorders (5). This infant underwent decompressive endoscopic tunnel craniectomy at four weeks of life due to elevated intracranial pressures. Future decompressive procedures were planned for 4 -6 months of age. Like our patient, underdeveloped maxillary bones frequently seen in Pfeiffer syndrome causes shallow orbits leading to proptosis. This could in return lead to damage to the cornea and/or exposure keratosis. It is necessary to add artificial tear ointment to prevent further damage. This maxillary hypoplasia could also lead to small larynx and pharynx which leads to respiratory distress and possible aspiration of food in to the lungs. In our patient, a G-tube was placed to prevent this scenario. Current treatment mode from 2013 recommends Genetics counseling and surgical treatment (2). In the first stage or the first year of life, the synostotic sutures should be released to decompress the brain and for remodeling of the skull to reduce the risk of hydrocephaly. In the second stage, a midfacial surgery is indicated to reduce the exophthalmos and midfacial hypoplasia. Case Report Our patient was delivered via C-section due to prolonged descent after an unremarkable pregnancy. She was 3. 2 kg in weight (50 th percentile), head circumference was 32. 5 cm (5 -10 th percentile) and the height was 49. 6 cm (50 th percentile). Mom was gravid 3, para 2, 40 year old Hispanic female. Her parents are phenotypically normal and denied consanguinity. The mother had two other healthy children. Labor began spontaneously and patient had APGAR scores of 8 and 9 at 5 and 10 minutes of life, respectively. Blood gases at delivery were unremarkable and infant was stable on room air. Physical exam showed closed sagittal sutures, lateral fusion of the coronal suture, open temporal, metopic, and lambdoid sutures. Midfacial hypoplasia along with a flat nasal bridge and a small mandible was also noted. Bilateral exophthalmos as well as low set ears were present. To check for choanal atresia, a 5 fr catheter was passed with difficulty through both nares. Breath sounds were present, however, noisy upper airway sounds were heard. Infant had good range of motion of extremities, including the elbows. Syndactyly of second and third digits of hands and feet were present. She had short phalanges and broad distal phalanges. The rest of the physical exam was unremarkable. A skeletal survey (image A, B, C) showed characteristic features of Pfeiffer syndrome which included clover leaf deformity, small shallow orbits, broad great toes with deformed metatarsals and phalanges, supernumerary digit on left hand, partial syndactyly of the bones and index fingers of both hands, and possible radioulnar synostosis on the left. A maxillofacial CT showed multiple bone abnormalities and ruled out choanal atresia in our patient. As there is a concern for visceral abnormalities with Pfeiffer’s syndrome, a chest x-ray and an echocardiogram were done. CXR was normal and the echo showed a small midmuscular VSD with left to right shunt and a small patent foramen ovale with left to right shunt. An MRI of brain and spine showed brachycephaly with marked deformity of the frontal calvarium and upward displacement of the frontal lobes. No hydrocephaly or intracranial hemorrhage was seen. An Upper GI showed normal gastric emptying and no structural abnormalities. Patient at 2 months of age in Endocrine clinic Genetics provided information regarding Pfeiffer Syndrome. Genetics has clinically diagnosed patient with Pfeiffer Syndrome type 2 and counseled the family on our patient’s likely developmental delay and intellectual disability. The genetics team also discussed a possible early death from breathing problems and other complications due to structural abnormalities. Our patient’s mother had bilateral tubal ligation and will not have additional children. Besides a consult to Genetics and Neurosurgery, general surgery was also consulted for poor feeding and concern for aspiration due to uncoordinated suck. A G-tube was placed prior discharge home. Craniofacial team will also follow and she will receive surgeries as indicated. Due to some incidence of pituitary insufficiency in this syndrome, Endocrine was to follow up with patient’s TFTs, free T 4 and cortisol levels. . A B C A. Cloverleaf skull deformity, small shallow orbits B. Broad great toes C. Supernumerar y digit and partial syndactyly of left hand Syndromes Ultrasound features Frequency of cloverleaf skull Etiology Apert Craniosynostosis, ocular proptosis, mid-face deficiency, syndactyly Rare Autosomal dominant, mostly sporadic Carpenter Craniosynostosis, preaxial polysyndactyly of feet, brachydactyly and clinodactyly with variable syndactyly of hands, congenital heart defects Rare Autosomal recessive Crouzon Craniosynostosis, ocular proposis, midface deficiency, No hand & foot anomaly (2) Uncommon Autosomal dominant Pfeiffer Craniosynostosis, ocular proptosis, midface deficiency, broad thumbs and great toes, variable soft tissue syndactyly of other digits Common Autosomal dominant Conclusions Our patient presents with a typical case of Pfeiffer Syndrome type 2 at LBJ Hospital in Houston, Texas. A review of literature illustrates Pfeiffer Syndrome type 2 as an autosomal dominant syndrome that presents with craniosynostosis with broad phalanges. The presentation of this syndrome is highly variable even within the same family. Thus, the treatment differs with each case. Surgery is opted for in many of the cases to decompress the brain. Pfeiffer syndrome is a rare genetic disorder that has better outcome with early intervention. However, the risk of early death is possible due to secondary complications from the syndrome itself. References 1. Bernstein PS, Gross SJ, Cohen DJ, Tiller GK, Shanske AL, Bombard AT, Marion RW. Prenatal Diagnosis of Type 2 Pfeiffer Syndrome. 2003; 8(6) 425 -428. 2. Fryns JP, Pfeiffer Syndrome. Orphanet J Rare Dis. 2006; 1: 19. 3. Jay S, Wiberg A, Swan M, Lester T, Williams LJ, Taylor IB, Johnson D, Wilkie A. The Fibroblast Growth Factor Receptor 2 p. Ala 172 Phe Mutation in Pfeiffer Syndrome—History Repeating Itself. American Journal of Medical Genetics. 2013; 161(5): 1158 -1163. 4. Oyamada MK, Ferreira H, Hoff M. Pfeiffer Syndrome Type 2—Case Report. Sao Paulo Medical Journal. 2003; 121(4) 176 -179. 5. Park MS, Yoo JE, Chung J, Yoon SH. A Case of Pfeiffer Syndrome. Journal of Korean Medical Science. 2006; 21(2) 374 -378. Texas Pediatric Society Electronic Poster Contest