P0865 - A case of an infant with Pentasomy X and airway malformations

Introduction:
Pentasomy X (49, XXXXX) syndrome is a rare chromosomal aneuploidy that occurs in females with an unknown incidence and prevalence. To date, there have been less than 30 described cases in the literature. Its origin is presumed to be a sporadic nondisjunction mutation during meiosis that results in three extra chromosomes (1). Many characteristic anomalies of the syndrome have been previously described, including musculoskeletal and cardiac anomalies, as well as facial dysmorphism. Associated respiratory malformations have not been previously described, however. We present a female infant with Pentasomy X with a novel finding of tracheomalacia and bronchomalacia. This malformation may signify that additional anomalies characterize this syndrome than once previously described.

Case Presentation:
Our patient presented with failure to thrive in the newborn period. She had several clinical features suggestive of an underlying genetic malformation, including microcephaly, a wide and flat nasal bridge, a right pre-auricular pit, short neck, short extremities, fifth finger clinodactyly, overlapping toes, and generalized hypotonia. Additionally, she had a prominent murmur on examination. This was investigated via echocardiogram, which revealed a moderate sized ASD, a PDA, and mild mitral and tricuspid regurgitation. Her genetic work-up included a karyotype, which revealed 49, XXXXX chromosomal aneuploidy.

Her infant course was complicated by repeated upper and lower respiratory tract infections, which often required hospitalization for escalating oxygen support. One such admission was further complicated by congestive heart failure. An echocardiogram at that time revealed moderate right heart dilation and high pulmonary artery pressures. Given these findings, a bronchoscopy was performed, which revealed mild tracheomalacia and severe left bronchomalacia.

As a result of these findings, the patient ultimately underwent early repair of her congenital heart defect and airway splinting of her airway malformation.

Discussion:
This rare genetic polysomy syndrome is usually diagnosed postnatally once concerning manifestations are noted. Craniofacial abnormalities, cardiovascular malformations, and musculoskeletal findings have been previously well described in Pentasomy X syndrome. About three cases thus far have been reported with congestive heart failure before one year of age (2). No cases have noted any pulmonary malformations, which leads us to consider whether the finding in our patient was sporadic or is a characteristic manifestation of Pentasomy X.

Conclusion:
Airway malformations may be a characteristic finding seen in Pentasomy X, however, more cases need to be reported in order to support this association.

References
1. Moraes LM, Cardoso LC, Moura VL, Moreira MA, Menezes AN, Llerena JC, et al. Detailed analysis of X chromosome inactivation in a 49,XXXXX pentasomy. Mol Cytogenet. 2009 Oct 7;2:20.
2. Demirhan O, Tanriverdi N, Yilmaz MB, Kocaturk-Sel S, Inandiklioglu N, Luleyap U, et al. Report of a new case with pentasomy X and novel clinical findings. Balkan J Med Genet. 2015 Jun;18(1):85–92.