Rubinstein-Taybi syndrome (RSTS), a rare autosomal dominantly inherited disease, is characterized by slow mental and physical growth, skeletal abnormalities (broad thumbs and big toes), and dysmorphic facial features (1). Other manifestations of RSTS include heart defects, genitourinary and central nervous system malformations, skin anomalies, and an increased predisposition to cancer (2). RSTS is mainly caused by de novo variants in the epigenetic-associated gene CREBBP (3). Moreover, the diagnosis of RSTS mainly depends on clinical manifestations and genetic testing.

Cutis marmorata telangiectatica congenita (CMTC) is a rare, congenital, and benign vascular anomaly of unknown etiology (4). It is described as a persistent reticulated, marbled erythema that blanches with pressure and does not resolve with heating. As it affects capillaries and venules, it is characterized by a slow-flow vascular lesion (5). The diagnosis of CMTC is primarily based on clinical features. Recently, GNA11 mutations have been reported to be associated with CMTC (6–8).

In the present study, we report the case of a preterm infant boy with RSTS and CMTC who presented with a novel frameshift mutation leading to a premature stop codon in the CREBBP gene. The child, with a typical facial appearance, experienced feeding difficulties, growth regression, and recurrent respiratory infections.

A boy, born at 34 weeks gestation, was transferred to our neonatal department after birth, requiring surfactant therapy and mechanical ventilation because of respiratory distress syndrome. The Apgar scores were 9–10–10. He weighed 2230 g (25th–50th percentile), was 43 cm long (10th–25th percentile), and his head circumference was 30 cm (10th–25th percentile). The patient presented with respiratory distress and polydactyly in both legs. In addition to the scalp, palm, sole, and mucous membranes, his entire body was covered with reticular marble-resembling flower-like macules (Figure 1). The skin changes did not disappear as the temperature in the environment increased. There was no family history of vascular malformation. No other congenital or neurological anomalies were observed. Repeat ultrasound examinations of the head and ophthalmological examinations were normal. Electroencephalography (EEG) and brain magnetic resonance imaging (MRI) revealed no abnormalities. Ear emission and auditory evoked potentials were normal, and echocardiography findings showed patent foramen ovale (PFO). Urinary ultrasound was normal, and thyroid function test results were all within normal limits. Due to respiratory distress and feeding difficulties, the patient stayed in the intensive care unit for approximately three months. Despite receiving antibiotics, respiratory support, and nasal feeding, his weight was 3800 g (<3rd percentile), his height was 53 cm (3rd–10th percentile), and his head circumference was 35 cm (<3rd percentile). In addition to microcephaly, he had arched eyebrows, down-slanting palpebral fissures, a broad nasal bridge, a triangular mouth, and broad big toes (Figure 1). At the age of four months, his Geisel score was equivalent to 4–8 weeks. In addition, the reticular marble-resembling flowers-like macules that covered his body didn't disappear.

During the most recent follow-up, at the time of writing this manuscript, the patient was two years old, could only speak a few words, and could not walk independently.

The baby covered with reticulated marbled erythema had dysmorphic facial features, broad toes, and mental and developmental delays. Our hypothesis is a diagnosis of RSTS with CMTC. However, genetic testing is required to confirm.

When RSTS was suspected, the clinical findings were supplemented with CREBBP sequencing using next-generation genotyping techniques. Sequencing reactions were performed using the MiSeq Illumina sequencer, and data analysis was performed using the MiSeq Reporter. CREBBP sequencing revealed a C duplication at position c.5837 in the CREBBP gene (c.5837dupC), a frameshift mutation predicted to result in premature termination at the 1966th amino acid of the CREB-binding protein (p.Pro1947Thrfs*19). Neither parent had any abnormalities at this site (Figure 2). Therefore, RSTS was confirmed.