Abstract
Background information:
Ectodermal dysplasia (ED) is a rare heterogeneous group of genetic disorders of ectodermal derived tissues, characterized by abnormalities in skin, teeth, hair and eccrine glands. Growth failure in these children varies depending on the genetic mutation and has not been well characterized. This clinical case report presents a 11-year-old male with a heterozygous mutation in WNT 10 A, a variant of the hypohydrotic ED gene, who was found to have growth hormone (GH) deficiency and treated with GH.
Case report:
He was born at 35 weeks gestation by C-section with a birth weight of 5 lbs. 12 oz. to a mother who had invitro fertilization with donor eggs from the maternal aunt with ocular myasthenia gravis and sperm from the father. Pregnancy was complicated by twin gestation and polyhydraminos. He had transient myasthenia gravis and treated with pyridostigmine for 3 months for feeding problems and swallowing difficulty. He also had arthrogryposis of the distal upper extremities attributed to placental transfer of the maternal aunt’s myasthenia gravis antibodies.
He was referred to the endocrine clinic for evaluation of his growth failure around the age of 8 years. His growth chart indicated that he grew along the 5thpercentile until age 5 year with a gradual decline to the 3rd percentile by age 7 year and close to 2nd percentile by age 8 year. His BMI was at 7th percentile. Mid parental height was 5’9”. There was no history of delayed adolescence in the family. His twin sister had very mild form of arthrogryposis with dental delay but steady linear growth. He also had decreased exercise tolerance. His body tended to become hot during sports activities and had to wrap his face and neck with cold soaked towels. His other problems included delayed dental development with conical incisor, thin nail, missing teeth and hearing defects that raised suspicion for ectodermal dysplasia. Genetic testing at the age of 4 years had demonstrated a heterozygous mutation in the WNT 10A gene, an important gene for tooth development. Physical examination revealed a mild facial dysmorphism with conical incisor, missing teeth and high arched palate. He had contracture of the proximal inter phalangeal joints of the hands. Investigations revealed a normal thyroid function test, IGF-1 and IGFBP-3 level, CBC, sedimentation rate, chemistry panel and celiac titer. The bone age was concordant with his chronological age of 8 years. A GH stimulation study demonstrated a peak GH level of 4.94 ng/ml. An MRI of the brain revealed a normal pituitary gland. He was started on GH therapy with 0.3 mg/kg/week at age 9 year. His height improved from 2nd percentile at age 9 year to 20th percentile by age 11 year on growth hormone therapy. His exercise capacity and stamina also improved.
Conclusion:
Growth failure and GH axis should be evaluated in children with ED. GH therapy improves growth velocity and exercise capacity in patients with ED.
231 A mutation in the SAM domain of p63 causing a mild ectodermal dysplasia phenotype