Primrose syndrome consists of recognizable facial features, macrocephaly, mental retardation, enlarged and calcified external ears, sparse body hair, and distal muscle wasting (summary by Carvalho and Speck-Martins, 2011).
Primrose (1982) described the single case of a 33-year-old mentally retarded male who had been institutionalized from the age of 12 years. The parents were not related. He showed progressive wasting of the distal muscles of the legs ... Primrose (1982) described the single case of a 33-year-old mentally retarded male who had been institutionalized from the age of 12 years. The parents were not related. He showed progressive wasting of the distal muscles of the legs and later of the small muscles of the hands. The cartilage of each pinna was extensively ossified, and photographs showing a fracture were presented. Cystic changes were observed in the head of the humerus and of the femurs, with deformity or destruction of the articular surfaces. Bilateral circumscribed, whitish, paracentral posterior polar cataracts were also described. He had had recurrent attacks of bilateral otitis media and was somewhat deaf. There was a 'hard mass filling in the cavity of the hard palate' which was not radioopaque. The same condition may have been described by Collacott et al. (1986). Their patient had large, calcified pinnae, and the buccal cavity was reduced by a large, soft-tissue mass extending over the inferior surface of the hard palate. Both lower limbs were wasted distally, and the hands were small and wasted. He had had recurrent attacks of otitis media and was profoundly deaf; he had dense bilateral cataracts. Lindor et al. (1996) described a third affected male who also had schizophrenia. Mathijssen et al. (2006) described a mentally retarded adult man who had joint contractures, sparse body hair, hearing loss, dysmorphic facial features, and, as cardinal features suggesting Primrose syndrome, large calcified pinnae and a huge torus palatinus. In addition, he developed a germ cell tumor of his right testicle at age 27 years. It was uncertain whether an increased risk of malignancy forms part of this syndrome or is only a consequence of cryptorchidism in the patient reported. Dalal et al. (2010) reported a 43-year-old woman with all the clinical elements of Primrose syndrome who remained undiagnosed for over 4 decades. She was born with congenital heart disease, hip dysplasia, and agenesis of the corpus callosum. In childhood, she was noted to have hearing impairment, cataracts, neoplasm of the bone in the palate, ossification of cartilage, cystic bone changes, diabetes mellitus, and hypothyroidism. She walked at age 6 years and was severely mentally retarded. She slowly lost the ability to walk, had distal muscle wasting, and needed a wheelchair by age 40. She had dysmorphic facial features, including micrognathia, anteverted nares, prominent ears and nasal root, ptosis, and microphthalmia. She also had spastic paraparesis, areflexia, motor tics, hand stereotypies, and self-flagellating behaviors. Brain MRI showed partial calcification of the basal ganglia, and laboratory studies showed increase serum calcitonin. Microarray analysis detected a small 225.5-kb deletion on chromosome 11p between dbSNP rs12275693 and dbSNP rs1442927 encompassing the BBOX1 gene (603312). Dalal et al. (2010) postulated an abnormality in calcium homeostasis. Carvalho and Speck-Martins (2011) described a 23-year-old Brazilian man, born of nonconsanguineous parents, who had mental retardation and developmental delay, macrocephaly, wide forehead, broad face, deeply set eyes, downslanting palpebral fissures with mild ptosis, large ears, high nasal bridge, large jaw, and apparently small mouth. The ears were unusually firm and immobile. He had thoracic kyphosis but no scoliosis, and genu valgum with distal muscle wasting of the lower extremities was apparent. Ankles and elbows had mild reduction of mobility. He also displayed sparse body hair and thin, dystrophic fingernails and toenails. There was scaly, thickened skin over extensor joint surfaces, and a great number of pigmented nevi as well as some striae were present. Examination at 23 years of age showed poor coordination and mild bradykinesia, but follow-up over 2 decades did not reveal progressive neurologic involvement. Hearing loss was not clinically noticeable, but audiometric evaluation detected a bilateral moderate mixed hearing loss. Skeletal x-rays showed calcification of the ear cartilages, thoracic kyphosis, and sloping ribs; osteopenia was not noted. CT of the head revealed uniform and extensive calcification of both pinnae and part of the external ear canals, with no brain calcification. Echocardiography showed signs of concentric left ventricular remodeling. Carvalho and Speck-Martins (2011) reviewed the key features of the 7 reported patients with Primrose syndrome, noting that all cases had been sporadic, with no familial occurrence or consanguinity.