Letter to the Editor

Abstract

18 June, 2009 Dear Editor, DUODENAL ATRESIA: CONSIDER FEINGOLD SYNDROME Duodenal atresia affects one in 6000 births and is usually isolated. Feingold syndrome is an autosomal dominant cause of upper intestinal atresia (oesophagus or duodenum), digital anomalies and microcephaly. Infants with either atresia should be assessed for short middle phalanges (brachymesophalangy) of the 2nd and 5th fingers, cutaneous toe syndactyly and microcephaly. The presence of these signs should prompt further evaluation with hand X-rays, echocardiography, renal imaging, audiology and genetics consultation. We highlight this recommendation with the description of a neonate initially thought to have isolated duodenal atresia ultimately diagnosed with Feingold syndrome, confirmed by MYCN sequence analysis. The term female neonate with birthweight 3.16 kg (10th percentile), length 50 cm (50–90th percentile) and head circumference 32 cm (10th percentile) developed bilious vomiting after birth. Abdominal X-ray suggested duodenal atresia confirmed and repaired by laparotomy on day 3. As she had mild microcephaly, genetic consultation was requested (Fig. 1). Subtle digital anomalies including brachymesophalangy and bilateral clinodactyly of the 2nd and 5th fingers, broad feet, short toes and bilateral 4th/5th toe syndactyly were noted. Echocardiography, renal ultrasound and karyotype were normal. Hand X-rays confirmed hypoplasia of the middle phalynx of the index and little fingers (Fig. 2). Parental hands, feet and head circumference were all normal. Microcephaly and subtle dysmorphic features. Plain X-ray of the left hand demonstrating hypoplasia of the middle phalanx of the 2nd and 5th digits. MYCN sequence analysis detected a ‘de novo’ heterozygous 6 base pair frameshift deletion in exon 3, confirming the clinical diagnosis of Feingold syndrome. On follow-up at 13 months, she was developmentally appropriate. Her height was on the 10–25th percentile, weight 25–50th percentile and head circumference below the 2nd percentile. The commonest syndrome association with duodenal atresia is trisomy 21, present in 24% of affected neonates1 in one series. A less common association is Feingold Syndrome (OMIM #146280), first described in 1975 as a clinically variable autosomal dominant condition characterised by microcephaly, digital anomalies and intestinal atresia2, 3 caused by heterozygous mutations in MYCN gene.4 The combination of mild-moderate microcephaly and digital anomalies is highly suggestive of Feingold syndrome.3 The most consistent clinical features, present in almost all affected cases, are brachymesophalangy of the second and fifth fingers and cutaneous toe syndactyly, typically of fourth and fifth toes.3, 5 Ninety percent of affected patients have a head circumference less than the 10th percentile and up to 55% have gastrointestinal atresia, typically of the oesophageus or duodenum.5 Approximately half have intellectual disability, usually mild-moderate. Ten percent have hearing loss. Cardiac and renal anomalies may also be present. Suggestive facial features include short palpebral fissures and micrognathia. VACTERL association is often a consideration. Feingold syndrome has complete penetrance, but variable expressivity, so may be unrecognised in the parent of an affected child.5 A family history of gastrointestinal atresia should be sought and the parents should be carefully assessed with measurement of head circumference and examination of the hands and feet. A MYCN gene mutation is identified in 75% of patients with clinically suspected Feingold syndrome, suggesting other genes may be involved in this syndrome. All mutations result in haploinsufficiency, suggesting that gene dosage is important in embryogenesis and post-natal head growth,4 although the exact mechanism is not understood. MYCN mutation detection confirms the diagnosis and allows for accurate genetic counselling about recurrence. In summary, Feingold syndrome is a rare cause of upper intestinal atresia. Infants with intestinal atresia should be routinely evaluated for digital anomalies and microcephaly. Although rare, recognition of this condition is important for genetic counselling and ongoing management. The authors acknowledge Dr EJ Kamsteeg and Dr FA Hol at the DNA laboratory KGCN (Klinisch- Genetisch Centrum Nijmegen) for performing MYNC sequence analysis. We would also like to thank the parents for their consent to publish this article. Answer: This baby has staphylococcal scalded skin syndrome. It is caused by toxin-producing strains of Staphylococcus aureus, which can be either sensitive strains or methicillin-resistant.