Author: Michael A. Evans, MD – Ann & Robert H. Lurie Children’s Hospital of Chicago, Northwestern Feinberg School of Medicine
A 7kg 11-month-old infant with a history of double outlet right ventricle, pulmonary atresia, and palliation to a bidirectional Glenn presents for orthotopic heart transplantation due to severe ventricular dysfunction. On exam, the patient is noted to be small for chronologic age, has broad thumbs and great toes, microcephaly, a prominent nose with nasal septum extending below the alae nasi, and a high-arched palate. Which of the following syndromes is MOST likely to be diagnosed in this patient?
Correct!
Wrong!
Question of the Week 336
Rubinstein-Taybi Syndrome (RTS or RSTS) or Broad Thumb-Hallux Syndrome is a syndrome characterized by short stature, intellectual disability, characteristic facial appearance, broad thumbs, and broad great toes. Approximately 33% of patients with RST have congenital heart disease (CHD) with average age at diagnosis of 6.4 months. RTS is most commonly caused by a disruption of the CREBBP gene on chromosome 16, which encodes the CREB-Binding Protein, and is estimated to affect 1 in 300,000 live births.
There are no standard diagnostic criteria for RTS due to the wide variability in phenotypes for patients and as such, RTS is most often a clinical diagnosis. Concurrent failure to thrive, microcephaly, dysmorphic facial features, broad thumbs and great toes lead to a presumed diagnosis until there is confirmatory genetic testing. The distinct thumb and toe abnormalities are unique to this syndrome.
Down syndrome or Trisomy 21, is a genetic disorder caused by a third copy of chromosome 21. Similar to RTS, it is a syndrome that is characterized by growth delays, intellectual disability, and characteristic facies. Forty percent of children diagnosed with Trisomy 21 have CHD. The characteristic facies of Trisomy 21 include up-slanting palpebral fissures, epicanthic folds, a flat nasal bridge, and macroglossia. Many patients with Trisomy 21 do possess a gap between the first and second toes.
DiGeorge syndrome, also known as 22q11.2 Deletion Syndrome, occurs due to a microdeletion on the long arm of chromosome 22. It has an estimated prevalence of 1 in 4000 live births and is the most common microdeletion syndrome. Patients with DiGeorge Syndrome also have characteristic facial features, cognitive impairment, CHD (particularly conotruncal defects), and palate abnormalities. The characteristic facial features include retro- or micrognathia, high and broad nasal bridge, small teeth with downturned mouth, short philtrum, low-set ears, and hypertelorism.
Noonan syndrome is an autosomal dominant disease that involves multiple organ systems. It is the second most common syndromic cause of CHD after Trisomy 21. Cardiac manifestations vary widely, but pulmonary stenosis, hypertrophic cardiomyopathy (HCM), and atrial septal defect (ASD) are the most common findings. The syndrome is also associated with distinctive facies (coarse features with tall forehead and low posterior hairline in infancy), developmental delay, and short stature.
References
1. Wiley S, Swayne S, Rubinstein JH, Lanphear NE, Stevens CA. Rubinstein-Taybi syndrome medical guidelines. Am J Med Genet A. 2003;119A(2):101-110. doi:10.1002/ajmg.a.10009
2. Stevens CA, Bhakta MG. Cardiac abnormalities in the Rubinstein-Taybi syndrome. Am J Med Genet. 1995;59(3):346-348. doi:10.1002/ajmg.1320590313
3. Rubinstein JH, Taybi H. Broad thumbs and toes and facial abnormalities. A possible mental retardation syndrome. Am J Dis Child. 1963;105:588-608. doi:10.1001/archpedi.1963.02080040590010
4. Rubinstein JH. Broad thumb-hallux (Rubinstein-Taybi) syndrome 1957-1988. Am J Med Genet Suppl. 1990;6:3-16. doi:10.1002/ajmg.1320370603
5. Loomba RS, Geddes G. Tricuspid atresia and pulmonary atresia in a child with Rubinstein-Taybi syndrome. Ann Pediatr Cardiol. 2015;8(2):157-160. doi:10.4103/0974-2069.154151
6. Roberts AE, Allanson JE, Tartaglia M, Gelb BD. Noonan syndrome. Lancet. 2013;381(9863):333-342. doi:10.1016/S0140-6736(12)61023-X
7. Bassett AS, McDonald-McGinn DM, Devriendt K, et al. Practical guidelines for managing patients with 22q11.2 deletion syndrome. J Pediatr. 2011;159(2):332-339. doi:10.1016/j.jpeds.2011.02.039
There are no standard diagnostic criteria for RTS due to the wide variability in phenotypes for patients and as such, RTS is most often a clinical diagnosis. Concurrent failure to thrive, microcephaly, dysmorphic facial features, broad thumbs and great toes lead to a presumed diagnosis until there is confirmatory genetic testing. The distinct thumb and toe abnormalities are unique to this syndrome.
Down syndrome or Trisomy 21, is a genetic disorder caused by a third copy of chromosome 21. Similar to RTS, it is a syndrome that is characterized by growth delays, intellectual disability, and characteristic facies. Forty percent of children diagnosed with Trisomy 21 have CHD. The characteristic facies of Trisomy 21 include up-slanting palpebral fissures, epicanthic folds, a flat nasal bridge, and macroglossia. Many patients with Trisomy 21 do possess a gap between the first and second toes.
DiGeorge syndrome, also known as 22q11.2 Deletion Syndrome, occurs due to a microdeletion on the long arm of chromosome 22. It has an estimated prevalence of 1 in 4000 live births and is the most common microdeletion syndrome. Patients with DiGeorge Syndrome also have characteristic facial features, cognitive impairment, CHD (particularly conotruncal defects), and palate abnormalities. The characteristic facial features include retro- or micrognathia, high and broad nasal bridge, small teeth with downturned mouth, short philtrum, low-set ears, and hypertelorism.
Noonan syndrome is an autosomal dominant disease that involves multiple organ systems. It is the second most common syndromic cause of CHD after Trisomy 21. Cardiac manifestations vary widely, but pulmonary stenosis, hypertrophic cardiomyopathy (HCM), and atrial septal defect (ASD) are the most common findings. The syndrome is also associated with distinctive facies (coarse features with tall forehead and low posterior hairline in infancy), developmental delay, and short stature.
References
1. Wiley S, Swayne S, Rubinstein JH, Lanphear NE, Stevens CA. Rubinstein-Taybi syndrome medical guidelines. Am J Med Genet A. 2003;119A(2):101-110. doi:10.1002/ajmg.a.10009
2. Stevens CA, Bhakta MG. Cardiac abnormalities in the Rubinstein-Taybi syndrome. Am J Med Genet. 1995;59(3):346-348. doi:10.1002/ajmg.1320590313
3. Rubinstein JH, Taybi H. Broad thumbs and toes and facial abnormalities. A possible mental retardation syndrome. Am J Dis Child. 1963;105:588-608. doi:10.1001/archpedi.1963.02080040590010
4. Rubinstein JH. Broad thumb-hallux (Rubinstein-Taybi) syndrome 1957-1988. Am J Med Genet Suppl. 1990;6:3-16. doi:10.1002/ajmg.1320370603
5. Loomba RS, Geddes G. Tricuspid atresia and pulmonary atresia in a child with Rubinstein-Taybi syndrome. Ann Pediatr Cardiol. 2015;8(2):157-160. doi:10.4103/0974-2069.154151
6. Roberts AE, Allanson JE, Tartaglia M, Gelb BD. Noonan syndrome. Lancet. 2013;381(9863):333-342. doi:10.1016/S0140-6736(12)61023-X
7. Bassett AS, McDonald-McGinn DM, Devriendt K, et al. Practical guidelines for managing patients with 22q11.2 deletion syndrome. J Pediatr. 2011;159(2):332-339. doi:10.1016/j.jpeds.2011.02.039
