aDepartment of Medical Genetics, McGill University, Montreal, Quebec, CanadabWellcome Trust Sanger InstitutecDepartment of Medical Genetics, University of Cambridge, Cambridge, UK
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List of key featuresBaraitser–Winter malformation syndrome ACTB Jejunal atresia Recurrent fevers Psoriatic arthropathyIntroductionBaraitser–Winter malformation syndrome (BWMS, OMIM 243310) is an autosomal dominant multisystem disorder characterized by typical craniofacial features, intellectual disability, brain malformation, iris or retinal coloboma, sensorineural deafness and muscle wasting resulting in a typical stance with kyphosis, anteverted shoulders and flexed flexion deformities of elbows and knees (Verloes et al., 2015). BWMS is caused by mutations in the cytoplasmic actin genes ACTB and ACTG1 (Rivière et al., 2012). To date, the association of BWMS with jejunal atresia, recurrent fevers or psoriatic arthropathy has not been reported. Here, we describe a 22-year-old male presenting with jejunal atresia, recurrent fevers and psoriatic arthropathy with typical dysmorphic, intellectual, joint and auditory features of BWMS. He was found to have a novel heterozygous pathogenic ACTB missense variant on whole exome sequencing (WES).Clinical summaryOur patient, now 22 years old, initially presented at birth with multiple jejunal atresias requiring a significant small bowel resection with subsequent short bowel syndrome and failure to thrive requiring ongoing gastrostomy and enteral feeding, further complicated by recurrent bouts of gastrointestinal bleeding. He was the result of a natural conception with the pregnancy significant for maternal abdominal pain, followed closely with nine normal prenatal ultrasounds. It was otherwise unremarkable. The parents were of English, Swedish and German descent with his mother and father having two and one unaffected offspring with different partners, respectively. Review of family history was noncontributory.At 3 years of age, he was noted to have sensorineural hearing loss, requiring bilateral hearing aids, thought at the time to be related to aminoglycoside exposure. The following year, he experienced an isolated seizure attributed to an electrolyte imbalance secondary to his short bowel syndrome treated with steroids. After weaning off steroids, he began to develop recurrent fevers with variable frequency and duration. These fevers occurred without an identifiable trigger, could last up to 5 days, can be associated with erythematous macules and are still ongoing. Around the age of 17 years, he developed psoriatic arthropathy treated with immunotherapy and weekly methotrexate. Recently, beginning at the age of 21 years, he developed a predominantly upper, left-sided peripheral neuropathy confirmed on electromyogram, with significant muscle wasting. The degree of muscle wasting has begun to impact his ability to perform his activities of daily living (ADL).In terms of intellectual development, our patient had a global developmental delay requiring a specialized school, physiotherapy and occupational therapy. He is currently regarded as having the mental abilities in the range of a 6–7 year-old child. He is described as naive and innocent, requiring assistance with all instrumental activities of daily living (IADL) as well as some ADLs.On physical examination, his growth parameters were under the third percentile for height and weight with a head circumference at the 90th percentile. His facial appearance displayed typical features of BWMS with a prominent brow, arched eyebrows, hypertelorism, ptosis, long downslanting palpebral fissures, broad nose with a large tip and prominent root and low set ears (Fig. 1). His posture, characteristic of BWMS, was defined by fixed flexion deformities of the elbows and knees, and anteverted shoulders (Fig. 2). In addition, on musculoskeletal examination, significant muscular atrophy was evident in his right hand, with limited strength and atrophic posturing. Skin examination revealed global follicular keratinous plugging sparing the facial region.