Brain anomalies, retardation of mentality and growth, ectodermal dysplasia, skeletal malformations, Hirschsprung disease, ear deformity and deafness, eye hypoplasia, cleft palate, cryptorchidism, and kidney dysplasia/hypoplasia BRESEK/BRESHECK: New X-link

Abstract

Two half brothers (maternally related) had a similar syndrome of microhydrocephaly in both brothers and dilatation of the spinal canal with fusion of thalami in one brother. Primordial growth delay was noted in both brothers, with severe mental retardation in the surviving brother. Both had ectodermal dysplasia with scaling, hyperkeratosis, and generalized alopecia, but normal sweat and sebaceous glands. Skeletal anomalies included hemivertebrae with abnormal segmentation in one and scoliosis with polydactyly in the other. Ears were apparently low set, large, and protruding, with mixed hearing loss in the brother who survived. Eye anomalies included maldevelopment of one eye in Patient 1 and small optic nerves more noticeable on one side in Patient 2. Both had cryptorchidism and dysplastic/hypoplastic kidneys of varying severity that resulted in the early postnatal death of one sib. Manifestations present in only one or the other sib included submucous cleft palate, aganglionosis of the rectum and colon, agenesis of one testicle, and single umbilical artery. This syndrome has not been described previously and may be due to an X-linked mutation. The acronym BRESEK reflects the common findings, whereas BRESHECK denotes all manifestations of both patients: brain, retardation, ectodermal dysplasia, skeletal deformities, Hirschsprung disease, ear/eye anomalies, cleft palate/cryptorchidism, and kidney dysplasia/hypoplasia. In addition to an X-linked mutation, a contiguous gene deletion or maternal mosaicism of an autosomal dominant gene must be considered.

Expanding the phenotype of IFAP/BRESECK syndrome: A new case with severe hypogammaglobulinemia

“…Other neurological features in this case were microcephaly, dilated ventricles and thin corpus callosum. These anomalies have been previously reported by several authors [8,10,15,16].…”

“…Recently a patient with the p.I258.M mutation was described with mild B cell lymphopenia and poor antibody response [6]. Other authors have reported atopic features like urticaria, atopic dermatitis, cow's milk protein allergy and anaphylaxis [3,4,11,16]. The presence of hypogammaglobulinemia in our patient might suggest a primary B lymphocyte disfunction in IFAP/BRESHECK syndrome playing a role in the pathogenesis of recurrent skin and respiratory tract infections.…”

Corpus Callosal Abnormalities in Dogs

“…Also, we found a previously unreported association with dermatologic conditions (hyperkeratosis and ichthyosis), mainly in the SBTs. Similar associations have been reported in human patients and a genetic cause is often suspected 20, 21…”

The contribution of associated congenital anomalies in understanding Hirschsprung’s disease

“…Polydactyly has been described as part of a syndrome of heart defects, laryngeal anomalies and HSCR [70,71] and other autosomal recessive syndromes in siblings [68]. HSCR has been associated with Werner mesomelic dysplasia [72], short stature [73] and the BRESHEK syndrome [74]. Osteopetrosis and HSCR were also reported in seven children born of consanguineous marriages [75].…”