Statistics from Altmetric.com
We therefore report on a female patient (birth weight 2150 g at 37 weeks’ gestation, maternal age 40 years, fifth child) born with the typical clinical features of trisomy 21. Chromosomal analysis confirmed the diagnosis. A positive family history of cystic fibrosis with an affected sister who died at the age of 14 years two years earlier, gave her a 25% risk for this disease too. A pathological sweat test (sodium chloride 180 mmol/l) and homozygosity for the mutation delta F508 on chromosome 7 confirmed the diagnosis of cystic fibrosis. Clinically she exhibited marked failure to thrive, malnutrition, signs of maldigestion, and recurrent pneumonia. Although the patient received intense treatment including antibiotics, high energy nutrition and enzyme replacement, her condition deteriorated gradually. She died at the age of 6 months.
Our patient is the first reported so far with DNA analysis confirming both diagnoses, cystic fibrosis and trisomy 21. Diagnosis of cystic fibrosis in the four patients reported previously relied on sweat tests and clinical features with respect to cystic fibrosis. However, abnormalities of osmolarity and sodium chloride concentrations of sweat were reported in trisomy 21, thus rendering the validity of sweat tests questionable.4 Also, as clinical symptoms such as failure to thrive, malnutrition, signs of maldigestion, and recurrent pneumonia could be easily attributed to either disease, clinical diagnosis is hampered. It is important to consider the diagnosis of cystic fibrosis in children with Down’s syndrome and the above clinical signs. DNA analysis is then essential in confirming or rejecting a diagnosis of cystic fibrosis.
The risk for the occurrence of trisomy 21 and cystic fibrosis in the general population is 1:1 200 000 (1:600 × 1:2000). In a family with one child suffering from cystic fibrosis the risk for siblings is increased (1:600 × 1:4 = 1:2400) and rises further with maternal age. Therefore, the coexistence of cystic fibrosis and trisomy 21 should be more frequent.
The prognosis in this combined disease seems to be very poor. None of the affected children reported survived longer than our patient.