Pediatric D e ~ a t o l o g yVol. 9 No. 2 103-106
Dyskeratosis Congenita Associated with Elevated Fetal Hemoglobin, X-Linked Ocular Albinism, and Juvenile-Onset Diabetes Mellitus Martin Reichel, M.D., Arthur C. Grix, M.D., and R. Rivkah Isseroff, M.D. Departments of Dermatology and Pediatrics, University of California, School of Medicine, Davis, California
Abstract: An 11-year-old boy had dyskeratosis congenita, elevated fetal hemoglobin level, X-linked ocular albinism, and juvenile-onset dlabetes mellitus. A review of the international literature revealed that elevated fetal hemoglobin has been noted in 15 reported cases of dyskeratosls congenita. It is a previously unrecognized, commonly associated finding in dyskeratosis congenita that may provide insight into the location and function of the gene for dyskeratosis congenita.
Dyskeratosis congenita, or Zinsser-Cole-Engman syndrome, is a rare, congenital disorder first described in 1906as atrophia cutis reticularis cum pigmentatione, dystrophia unguium et leukoplakia oris (1). It is characterized by the triad of poikilodermatous skin changes, dystrophic nails, and leukoplakia. Multisystem organ manifestations are associated with dyskeratosis congenita. Most notably, these children frequently develop an anemia that may progress to pancytopenia and death. Furthermore, they are at a significant risk for developing malignancies at an early age. Systemic findings have involved the skin, eyes, ears, bones, central nervous system, kidneys, and gastrointestinal and hematopoietic systems (2). Our patient was an I l year-old boy with dyskeratosis congenita, elevated fetal hemoglobin, X-linked ocular albinism, juvenile-onset diabetes mellitus, and asthma.
CASE REPORT
An 1I-year-old boy with a history of diabetes mellitus, X-linked ocular albinism, and asthma came to our institution complaining of progressive nail dystrophy over the past one and one-half years. There was no history of mental retardation, developmental delay, hematologic abnormality, or reported family member with a similar nail problem. The patient’s maternal uncle and a cousin have ocular albinism, and at age 6 months the patient was diagnosed with that condition. At age 18 months eye surgery was done to stabilize his nystagmus and strabismus. Surgery was repeated at 4.5 years and again at 5 years. At 20 months of age he was diagnosed as having insulin-dependent diabetes mellitus . Pertinent physical findings included 20 dystro-
Address correspondence to R. Rivkah Isseroff, M.D., TB 192, University of California, School of Medicine, Davis, CA 95616.
103
104 Pediatric Dermatology Vol. 9 No. 2 June 1992 phic nails characterized by thinning, longitudinal ridging, hypoplasia, and pterygium formation (Fig. I). The skin on his fingers was atrophic. He had a reticular, tan-silver-gray hyperpigmentation on the flexural arms bilaterally, with mild atrophy and telangiectasia (Fig. 2). A fine, reticulate, erythematous, scaly hyperpigmentation encircled the neck. White plaques and erosions were present on the lateral aspects of his dorsal tongue. The anus and urethra were without lesions. Given the constellation of clinical findings, a diagnosis of dyskeratosis congenita was made. Neurologic examination was noteworthy for a mild deviation of the tongue to the right, a mild intention tremor of the hands, and rapid horizontal nystagmus. Funduscopy demonstrated macular hypoplasia and decreased reticular pigmentation with increased visualization of the choroid vessels, consistent with the diagnosis of ocular albinism. Ishihara’s tests for color blindness were negative. A complete blood cell count and chemistry panel were normal except for glucose of 257 mg/dL. Hemoglobin AIC was elevated to 9.9% (normal 3 . 4 4 1 % ) . Hemoglobin was 12.4 gidl, hematocrit 35.3975, mean corpuscular volume 95.6 p3, white blood cell count 5.2 x 109/L, and platelets 242 X 1OY/L. Hemoglobin electrophoresis demonstrated an elevated hemoglobin F (HbF) of 7.5% (normal
Dyskeratosis Congenita Associated with Elevated Fetal Hemoglobin, X-Linked Ocular Albinism, and Juvenile-Onset Diabetes Mellitus Martin Reichel, M.D., Arthur C. Grix, M.D., and R. Rivkah Isseroff, M.D. Departments of Dermatology and Pediatrics, University of California, School of Medicine, Davis, California
Abstract: An 11-year-old boy had dyskeratosis congenita, elevated fetal hemoglobin level, X-linked ocular albinism, and juvenile-onset dlabetes mellitus. A review of the international literature revealed that elevated fetal hemoglobin has been noted in 15 reported cases of dyskeratosls congenita. It is a previously unrecognized, commonly associated finding in dyskeratosis congenita that may provide insight into the location and function of the gene for dyskeratosis congenita.
Dyskeratosis congenita, or Zinsser-Cole-Engman syndrome, is a rare, congenital disorder first described in 1906as atrophia cutis reticularis cum pigmentatione, dystrophia unguium et leukoplakia oris (1). It is characterized by the triad of poikilodermatous skin changes, dystrophic nails, and leukoplakia. Multisystem organ manifestations are associated with dyskeratosis congenita. Most notably, these children frequently develop an anemia that may progress to pancytopenia and death. Furthermore, they are at a significant risk for developing malignancies at an early age. Systemic findings have involved the skin, eyes, ears, bones, central nervous system, kidneys, and gastrointestinal and hematopoietic systems (2). Our patient was an I l year-old boy with dyskeratosis congenita, elevated fetal hemoglobin, X-linked ocular albinism, juvenile-onset diabetes mellitus, and asthma.
CASE REPORT
An 1I-year-old boy with a history of diabetes mellitus, X-linked ocular albinism, and asthma came to our institution complaining of progressive nail dystrophy over the past one and one-half years. There was no history of mental retardation, developmental delay, hematologic abnormality, or reported family member with a similar nail problem. The patient’s maternal uncle and a cousin have ocular albinism, and at age 6 months the patient was diagnosed with that condition. At age 18 months eye surgery was done to stabilize his nystagmus and strabismus. Surgery was repeated at 4.5 years and again at 5 years. At 20 months of age he was diagnosed as having insulin-dependent diabetes mellitus . Pertinent physical findings included 20 dystro-
Address correspondence to R. Rivkah Isseroff, M.D., TB 192, University of California, School of Medicine, Davis, CA 95616.
103
104 Pediatric Dermatology Vol. 9 No. 2 June 1992 phic nails characterized by thinning, longitudinal ridging, hypoplasia, and pterygium formation (Fig. I). The skin on his fingers was atrophic. He had a reticular, tan-silver-gray hyperpigmentation on the flexural arms bilaterally, with mild atrophy and telangiectasia (Fig. 2). A fine, reticulate, erythematous, scaly hyperpigmentation encircled the neck. White plaques and erosions were present on the lateral aspects of his dorsal tongue. The anus and urethra were without lesions. Given the constellation of clinical findings, a diagnosis of dyskeratosis congenita was made. Neurologic examination was noteworthy for a mild deviation of the tongue to the right, a mild intention tremor of the hands, and rapid horizontal nystagmus. Funduscopy demonstrated macular hypoplasia and decreased reticular pigmentation with increased visualization of the choroid vessels, consistent with the diagnosis of ocular albinism. Ishihara’s tests for color blindness were negative. A complete blood cell count and chemistry panel were normal except for glucose of 257 mg/dL. Hemoglobin AIC was elevated to 9.9% (normal 3 . 4 4 1 % ) . Hemoglobin was 12.4 gidl, hematocrit 35.3975, mean corpuscular volume 95.6 p3, white blood cell count 5.2 x 109/L, and platelets 242 X 1OY/L. Hemoglobin electrophoresis demonstrated an elevated hemoglobin F (HbF) of 7.5% (normal
