The proband, a female infant was the first of dichorionic-diamniotic (DCDA) twin girls born prematurely at 35 + 3 weeks gestation by elective caesarean section for discordant growth on ultrasound. She had a birth weight of 1650 g; her sister weighed 2510 g. This patient was a result of the sixth pregnancy of a nonconsanguineous couple; all other siblings are alive and well. The 35-year-old mother's past medical history was unremarkable except for latent TB infection; her only pregnancy complication was a finding of vitamin D deficiency. She received standard twin pregnancy antenatal care. Initial fetal morphology scans performed at 17 and 21 weeks gestation showed no abnormalities. Discordant growth was first detected at 26 weeks gestation and monitored with serial ultrasound. At 34+ weeks, ultrasound surveillance showed that the first twin's estimated weight had dropped below the third centile while amniotic fluid index and umbilical artery Doppler flows remained within normal limits; short femur length was also noted for the first time at this scan. Due to increasing growth discordance the decision was made for elective delivery at 35 weeks following betamethasone administration.
The patient required less than one minute of positive pressure ventilation at delivery for poor respiratory effort and was then stabilized on constant positive airway pressure (CPAP). Respiratory support was weaned without complication within the first hour of life. Dysmorphic features were first noted on day 10 of life when she was observed to have prominent epicanthic folds, broad nasal bridge, anteverted nares, simple ears, and bilateral overlapping fifth fingers (Figure 1). Further examinations and imaging were performed to assess for other dysmorphologies and no abnormalities were detected on renal ultrasound, ophthalmology examination, cranial ultrasound, or brain magnetic resolution imaging (MRI). Conventional chromosome analysis on peripheral bloods was requested.
The neonatal course was complicated by seizures occurring on day 22 of life. During these episodes she became pale and inactive and showed jerking movements of all four limbs and had a corresponding decrease in oxygen saturations. Each episode lasted for approximately 20 seconds which self-resolved, but she remained hypotonic for 2-3 minutes following this episode. Treatment was initiated for possible meningitis but colony stimulating factor (CSF) culture and viral studies were negative. No further episodes were noted after this.
A grade 3 systolic cardiac murmur was noted during admission. Subsequent echocardiogram showed a structurally normal heart with a small patent foramen ovale and normal cardiac function.
Persistent thrombocytopenia was documented with platelet nadir of 79 x 109/L on day 25 of life. Blood film analysis was not diagnostic of specific pathology and there was no clinical evidence of bleeding or bruising. All other haematological cell lines were normal.
The patient was discharged on day 63 of life at one month corrected gestational age on full suck feeds with a weight of 2265 grams. On review at 8 weeks corrected age weight gain was very slow with the patient's weight dropping significantly below the 3rd centile in association with poor feeding and decreased caloric. On examination she was markedly hypotonic with significant head lag but demonstrated some antigravity movement in all four limbs. Cardiac murmur was no longer audible.
At 4.5 months the patient died at home after struggling to gain weight. Gavage feeding was discussed but not proceeded with and parents had made a decision not to resuscitate. A postmortem was declined.