Rubinstein–Taybi syndrome in a late preterm neonate: A case report highlighting clinical diagnosis

INTRODUCTION

Rubinstein–Taybi syndrome (RTS) is a rare autosomal-dominant genetic disease, with an estimated prevalence of one case per 125,000 live births. It is typically associated with mutations in the CREBBP or EP300 genes.^[1] Clinical features include distinct craniofacial dysmorphisms, microcephaly, broad thumbs and toes, intellectual disability and postnatal growth retardation. Additional manifestations can include cardiac anomalies, central nervous system malformations and genitourinary or skin abnormalities.^[2]

CASE REPORT

A late preterm neonate, born to a 2^nd consanguineous couple with no significant antenatal complications, was admitted to the Neonatal Intensive Care Unit for respiratory distress. On examination, the infant exhibited multiple dysmorphic features: Broad and angulated thumbs and great toes, microcephaly, low-set ears, high-arched palate, micrognathia and retrognathia.

Syndromic evaluation was initiated. Magnetic resonance imaging of the brain revealed mild thinning of the corpus callosum.^[2] A 2D echocardiogram showed a small patent foramen ovale (PFO). Hearing evaluation was normal. Due to feeding difficulties, the infant required orogastric feeding initially and was later transitioned to non-nutritive sucking and paladai feeding, followed by successful breastfeeding. Kangaroo mother care (KMC) was initiated and continued at home. Genomic sequencing revealed no identifiable variants. The baby was clinically stable and discharged with multidisciplinary follow-up.

DISCUSSION

RTS is characterised by a constellation of physical anomalies and developmental delays, most frequently due to mutations in the CREBBP gene and occasionally in EP300.^[3] Diagnosis is often based on characteristic clinical features such as broad thumbs and toes, facial dysmorphism and neurodevelopmental delays.^[4] In this case, classical features were evident, including broad digits and craniofacial abnormalities, alongside neuroimaging findings consistent with mild thinning of the corpus callosum.^[2]

Feeding issues, especially in preterm infants with RTS, are common due to hypotonia and poor coordination, often requiring enteral support and a gradual transition to oral feeds.^[5] As seen in this case, the infant progressed from orogastric to breastfeeding with supportive interventions such as non-nutritive sucking and KMC.

The 2D echocardiogram showed a small PFO, a frequently reported finding in RTS, though often asymptomatic.^[3]

Normal hearing in this infant is encouraging, as approximately 30% of RTS patients exhibit hearing loss, necessitating regular auditory screening.

Although genomic sequencing did not reveal pathogenic mutations, a clinical diagnosis remains probable. Around 20– 30% of RTS cases lack identifiable mutations in the CREBBP or EP300 genes due to limitations of standard sequencing or the presence of de novo mutations.^[3,6]

CONCLUSION

This case emphasises the importance of clinical acumen in diagnosing RTS, especially when genetic confirmation is inconclusive. Characteristic features such as craniofacial dysmorphism, broad digits and neurodevelopmental findings should prompt early multidisciplinary intervention. Despite negative genetic testing, clinical suspicion based on phenotype remains critical. Continued follow-up, developmental assessment and screening for cardiac and auditory issues are essential to long-term care.