Silver-Russell syndrome and cystic fibrosis associated with maternal uniparental disomy 7

✍ Scribed by Hehr, Ute; D�rr, Sylvia; Hagemann, Monika; Hansmann, Ingo; Preiss, Uwe; Br�mme, Sabine

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 12 KB
• Volume: 91
• Category: Article
• ISSN: 0148-7299
• DOI: 10.1002/(sici)1096-8628(20000320)91:3<237::aid-ajmg17>3.0.co;2-8

✦ Synopsis

reported the first two cases of uniparental disomy (UPD) in men. Both patients were identified because of the observed autosomal recessive phenotype of cystic fibrosis (CF) resulting from homozygosity for a maternally inherited CFTR mutation. Prenatal and postnatal growth retardation in both patients were more severe than expected in individuals with CF alone. This marked growth retardation, typically combined with asymmetry and a distinct, relatively small triangular face, is today recognized as a significant feature of Silver-Russell syndrome (SRS) [Silver et al., 1953;Russell, 1954]. Most SRS cases are sporadic and genetic heterogeneity was established with one candidate region in 17q22-25 [Ramirez-Duenas et al., 1992;Midro et al., 1993]. In addition, maternal uniparental disomy 7 accounts for approximately 10% of the SRS patients [Kotzot et al., 1995;Eggermann et al., 1997;Preece et al., 1997].

Here we report the clinical and molecular data of a third patient with maternal UPD 7 and homozygosity for a CFTR mutation. The propositus is the first child of healthy, unrelated parents. There was no family history of CF or any other major disease. The propositus was delivered spontaneously at the 36th week of gestation after an uneventful pregnancy; he was small for gestational age (birthweight 1,760 g, length 44 cm, head circumference 31.5 cm; Apgar 08/09).

Two weeks postpartum an exocrine pancreas insufficiency was diagnosed. Subsequently, weight gain resumed under pancreas enzyme substitution. At 3 months molecular analysis of the CFTR gene was prompted because of the patient's gastrointestinal symptoms. It showed homozygosity for the common CFTR mutation ⌬F508 and the patient was referred to our CF clinic. At 5 months a more complex genetic problem was suspected because of the persistent severe growth retardation in combination with minor craniofacial anomalies. At clinical examination the patient presented with severe growth retardation: weight and length were below the 3rd centile (3,800 g, 59 cm).