Loss-of-Function GRHL3 Variants Detected in African Patients with Isolated Cleft Palate.

In contrast to the progress that has been made toward understanding the genetic etiology of cleft lip with or without cleft palate, relatively little is known about the genetic etiology for cleft palate only (CPO). A common coding variant of grainyhead like transcription factor 3 ( GRHL3) was recently shown to be associated with risk for CPO in Europeans. Mutations in this gene were also reported in families with Van der Woude syndrome. To identify rare mutations in GRHL3 that might explain the missing heritability for CPO, we sequenced GRHL3 in cases of CPO from Africa. We recruited participants from Ghana, Ethiopia, and Nigeria. This cohort included case-parent trios, cases and other family members, as well as controls. We sequenced exons of this gene in DNA from a total of 134 nonsyndromic cases. When possible, we sequenced them in parents to identify de novo mutations. Five novel mutations were identified: 2 missense (c.497C>A; p.Pro166His and c.1229A>G; p.Asp410Gly), 1 splice site (c.1282A>C p.Ser428Arg), 1 frameshift (c.470delC; p.Gly158Alafster55), and 1 nonsense (c.1677C>A; p.Tyr559Ter). These mutations were absent from 270 sequenced controls and from all public exome and whole genome databases, including the 1000 Genomes database (which includes data from Africa). However, 4 of the 5 mutations were present in unaffected mothers, indicating that their penetrance is incomplete. Interestingly, 1 mutation damaged a predicted sumoylation site, and another disrupted a predicted CK1 phosphorylation site. Overexpression assays in zebrafish and reporter assays in vitro indicated that 4 variants were functionally null or hypomorphic, while 1 was dominant negative. This study provides evidence that, as in Caucasian populations, mutations in GRHL3 contribute to the risk of nonsyndromic CPO in the African population.

Role of flaps and skin grafts in the management of neuropathic plantar ulcers

In the neurologically impaired foot pressure ulcers are common. Pressure point reduction must always be addressed. Most ulcers, perhaps with the exception of huge heel ulcers, will heal by secondary intention if treated conservatively in the right manner. However, conservative treatment can be very time consuming and might sometimes leave unstable scars. For those with recurrent ulcers, the time taken off work to heal these ulcers can be economically debilitating. Skin grafting and flep coverage can be rewarding in selected cases. Follow up with proper footwear is of uttermost importance. Soft tissue coverage can only occur when all signs of infection have resolved and the foot has an adequate blood supply.

[Surgical treatment of vaginal agenesia]. / Kirurgisk behandling ved vaginal agenesi.

BACKGROUND: Vaginal agenesia appears among 1 in 5,000-10,000 newborn girls, i.e. 3-6 patients per year in Norway. MATERIAL AND METHODS: From 1975 to 1998, 14 women (mean age 20 years) were operated for vaginal agenesia by McIndoe's method at Haukeland University Hospital. Twelve patients were examined 13 years later by questionnaire, gynaecological examination, ultrasound examination of the urinary tract, and blood and urinary test concerning kidney function and diabetes mellitus. RESULTS: Five patients had been re-operated within nine months because of contracture. In all patients (except one), the constructed vagina had good elasticity, width and depth. The donor area at the medial thigh was unaesthetic in four patients. No abnormalities were found in the urinary tract by ultrasound. One patients had a familial syndrome with Müllerian aplasia, progressive renal disease and mild diabetes mellitus. All patients found the operation important, despite memories of a painful postoperative period. INTERPRETATION: This study shows functional and psychological satisfactory results of construction of vagina in women with vaginal agenesia.

Salvage of a foot by free transplants from the contralateral leg in a 5-year-old.

A 5-year-old girl had a traumatic amputation of her left thigh and on the right side loss of the posterior part of the talus and parts of the posterior tibial nerve and artery. These defects were treated with free transplantation of the corresponding part of the talus from the amputated left leg and a vascularized graft from the left posterior tibial nerve and artery. 2 years later the girl was able to walk without crutches, the ankle mobility was good, and so was the sensibility in the sole of the foot.

Heel ulcer in leprosy treated with fasciocutaneous island flap from the instep of the sole.

Twenty-four leprous patients with longstanding ulcer of the weight bearing area of the heel underwent reconstruction by use of fasciocutaneous island flap from the instep. One flap was lost because the vascular pedicle was accidentally severed during the dissection. Infection delayed healing in three cases, and one patient developed minor necrosis of the edge of the flap without any adverse consequences. The remaining 18 cases healed without complications. Follow-up of 14 patients 3 to 10 months after the operation showed excellent results in all but the one whose flap was lost. The operation is recommended for difficult reconstructions of the heel.

Paediatric anaesthesia in a developing country.

A suitable anaesthetic technique was needed for oral surgery in infants in a developing country. As an air compressor was present, and oxygen accessible, a continuous flow technique was chosen. Two Boyle's machines--useless due to lack of soda lime and nitrous oxide--were converted without increasing susceptibility to technical and supplemental deficiencies. The challenge to simplify techniques without reducing patient safety is discussed, and the solutions in an Ethiopian hospital are presented.