American Journal of Medical Genetics 40124-125 (1991)
Letter to the Editor
Trichothiodystrophy and Ichthyosis as Diagnostic Signs To the Editor: I read with interest the article of Przedborski et al. [19901 addressing the genetic heterogeneity and diagnostic nonspecificity of trichothiodystrophy. To elaborate further on that I share the 8-year long observations of a “collodion” girl with trichothiodystrophy [Kousseff and Esterly, 19881. She was born small (birth weight 1,900 g, length 45.8 cm) after a 37-week uneventful gestation. Erythematous parchment-like skin and contractures at the large joints were noted (Fig. 1). A diagnosis of “collodion baby” secondary to lamellar ichthyosis (MIM #242300, Mendelian Inheritance in Man number [McKusick, 19901) was presumed. Physical therapy and skin care accompanied the slow physical and psychomotor growth throughout. At age 12 months, a skin biopsy showed keratosis with multifocal acanthosis, increased collagen fibrils, and lymphocytic infiltrates. A diagnosis of congenital ichthyosiform erythroderma (MIM #242100) was made. Sparse, slowly growing scalp hair led to light and electron microscopy of hair at age 19 months. The hair shafts had a wavy contour and in many areas were flattened and folded over. Trichoschisis and a few trichorrhexis nodosa-like fractures were noted. With polarized light, alternating bright and dark domains were seen in parts of the shaft (Fig. 2A). Scanning electron microscopy a t 300, 500, 800, and 1,000 magnification showed severe dystrophy of the shaft; the cuticle was replaced by an amorphous coat of debris with extensive cavitation (Fig. 2B). The sulfur content of the hair was markedly decreased: 1.83 r 0.43% (control4.61 & 0.12%).Thus, the hair findings indicated trichothiodystrophy [Price et al, 19801. Repeat skin biopsy showed a dense keratotic layer with a few keratin plugs. The granular layer was thin and the Malpighian layer was normal. No inflammatory changes were present. The impression was ichthyosiform dermatitis with histologic changes reminiscent of ichthyosis vulgaris (MIM #146700). Despite adequate caloric intake, the physical growth was slow throughout the years, and so was psychomotor
Received for publication May 2, 1990. Address reprint requests to Dr. Boris G. Kousseff,Department of Pediatrics, College of Medicine, University of S. Florida, Box 15-G, 12901 Bruce B. Downs Blvd., Tampa, FL 33612-4799.
0 1991 Wiley-Liss, Inc.
Fig. 1. Proposita: “collodion baby” phenotype at birth.
development. Serial psychometrics showed I& scores between 40 and 50. On Nutraderm, with 1%hydrocortisone, three times daily, the condition of the skin continued to improve. The hair remained sparse and did not grow longer than 2.5 cm. Tenotomies and neurectomy with casting improved the hip contractures and allowed ambulation. Solar hypersensitivity with blister formation became apparent. At age 6 years, the proposita was very small (height and weight 6 SD below the mean for chronologic age) and obviously mentally retarded. Ophthalmologic evaluation showed alternating exotropia, myopia, and multiple punctate opacities of fetal and juvenile nuclei of the lenses; the opacities did not impair the vision. Thyroid and pituitary function were normal. Scalp biopsy showed acanthosis, sparse hair follicles, and hypoplastic sebaceous glands. The outer root sheath was unremarkable. As in the previous study, the cuticle showed trichoschisis and marked disorganization. No one in the family had any of the problems of the proposita. While Przedborski et al. illustrate the genetic heterogeneity and the diagnostic nonspecificity of trichothiodystrophy, this reported patient indicates that the “ichthyosis” seen in patients with trichothiodystrophy is also nonspecific and heterogeneous. Tay syndrome [Tay,19711(MIM #242170), which appeared to be the accurate diagnosis for this patient, was diagnosed
Letter to the Editor
125
Fig. 2. Scalp hair. (A) Alternatingbright and dark bands seen with polarized microscopy. (B)Extensive cavitation of cuticle with amorphous debris (scanning EM X 500). ( C )Absent cuticle (scanning EM x 300).
after 8 years of clinical observation, repeat testing and change of diagnoses. It appears that, like any other organ, the integument including the hair has a limited number of ways in responding to varied noxae. Thus, regardless of cause, through the pathogenesis of the lesions, similar changes with considerable dynamics occur and cause diagnostic and genetic counseling dilemmas. For the phenotypic expression of the causative genetic and nongenetic factors, the pathogenesis appears to be the bottleneck and phenotypic similarities and overlap occur. Thus, caution has to be exercised whenever faced with not only trichothiodystrophy but with “ichthyosis” as well. Only longitudinal meticulous observations and repeat testing allow an accurate diagnosis with appropriate prognostications and genetic counseling for patients similar to this patient and the one reported by Przedborski et al. This is particularly pertinent to conditions without diagnostic biochemical and DNA markers.
REFERENCES Kousseff BG, Esterly NB (1988):Trichothiodystrophy, IBIDS Syndrome or Tay Syndrome? Birth Defects: Original Article Series 24(2):169-181,1990. McKusick VA (1990):Mendelian inheritance in man. “Catalogs of Autosomal Dominant, Autosomal Recessive, and X-linked phenotypes,” 9th edition. Baltimore: The Johns Hopkins University Press. Price VH, Odom RB, Ward WH, Jones FT (1980):Trichothiodystrophy: Sulfur-deficient brittle hair as a marker for a neuroectodermal symptom complex. Arch Dermatol 116:1375-1384. Przedborski S, Ferster A, Goldman S, Wolter R, Song M, Tprnnesen ‘T, Pollitt RJ, Vamos E (1990):Trichothiodystrophy, mental retardation, short stature, ataxia, and gonadal dysfunction in three Moroccan siblings. Am J Med Genet 35566-573. Tay C H (1971):Ichthyosiform erythroderma, hair shaft abnormalities, and mental and growth retardation. Arch Dermatol 104:4-13.
Boris G. Kousseff Department of Pediatrics University of S. Florida Tampa, Florida
Letter to the Editor
Trichothiodystrophy and Ichthyosis as Diagnostic Signs To the Editor: I read with interest the article of Przedborski et al. [19901 addressing the genetic heterogeneity and diagnostic nonspecificity of trichothiodystrophy. To elaborate further on that I share the 8-year long observations of a “collodion” girl with trichothiodystrophy [Kousseff and Esterly, 19881. She was born small (birth weight 1,900 g, length 45.8 cm) after a 37-week uneventful gestation. Erythematous parchment-like skin and contractures at the large joints were noted (Fig. 1). A diagnosis of “collodion baby” secondary to lamellar ichthyosis (MIM #242300, Mendelian Inheritance in Man number [McKusick, 19901) was presumed. Physical therapy and skin care accompanied the slow physical and psychomotor growth throughout. At age 12 months, a skin biopsy showed keratosis with multifocal acanthosis, increased collagen fibrils, and lymphocytic infiltrates. A diagnosis of congenital ichthyosiform erythroderma (MIM #242100) was made. Sparse, slowly growing scalp hair led to light and electron microscopy of hair at age 19 months. The hair shafts had a wavy contour and in many areas were flattened and folded over. Trichoschisis and a few trichorrhexis nodosa-like fractures were noted. With polarized light, alternating bright and dark domains were seen in parts of the shaft (Fig. 2A). Scanning electron microscopy a t 300, 500, 800, and 1,000 magnification showed severe dystrophy of the shaft; the cuticle was replaced by an amorphous coat of debris with extensive cavitation (Fig. 2B). The sulfur content of the hair was markedly decreased: 1.83 r 0.43% (control4.61 & 0.12%).Thus, the hair findings indicated trichothiodystrophy [Price et al, 19801. Repeat skin biopsy showed a dense keratotic layer with a few keratin plugs. The granular layer was thin and the Malpighian layer was normal. No inflammatory changes were present. The impression was ichthyosiform dermatitis with histologic changes reminiscent of ichthyosis vulgaris (MIM #146700). Despite adequate caloric intake, the physical growth was slow throughout the years, and so was psychomotor
Received for publication May 2, 1990. Address reprint requests to Dr. Boris G. Kousseff,Department of Pediatrics, College of Medicine, University of S. Florida, Box 15-G, 12901 Bruce B. Downs Blvd., Tampa, FL 33612-4799.
0 1991 Wiley-Liss, Inc.
Fig. 1. Proposita: “collodion baby” phenotype at birth.
development. Serial psychometrics showed I& scores between 40 and 50. On Nutraderm, with 1%hydrocortisone, three times daily, the condition of the skin continued to improve. The hair remained sparse and did not grow longer than 2.5 cm. Tenotomies and neurectomy with casting improved the hip contractures and allowed ambulation. Solar hypersensitivity with blister formation became apparent. At age 6 years, the proposita was very small (height and weight 6 SD below the mean for chronologic age) and obviously mentally retarded. Ophthalmologic evaluation showed alternating exotropia, myopia, and multiple punctate opacities of fetal and juvenile nuclei of the lenses; the opacities did not impair the vision. Thyroid and pituitary function were normal. Scalp biopsy showed acanthosis, sparse hair follicles, and hypoplastic sebaceous glands. The outer root sheath was unremarkable. As in the previous study, the cuticle showed trichoschisis and marked disorganization. No one in the family had any of the problems of the proposita. While Przedborski et al. illustrate the genetic heterogeneity and the diagnostic nonspecificity of trichothiodystrophy, this reported patient indicates that the “ichthyosis” seen in patients with trichothiodystrophy is also nonspecific and heterogeneous. Tay syndrome [Tay,19711(MIM #242170), which appeared to be the accurate diagnosis for this patient, was diagnosed
Letter to the Editor
125
Fig. 2. Scalp hair. (A) Alternatingbright and dark bands seen with polarized microscopy. (B)Extensive cavitation of cuticle with amorphous debris (scanning EM X 500). ( C )Absent cuticle (scanning EM x 300).
after 8 years of clinical observation, repeat testing and change of diagnoses. It appears that, like any other organ, the integument including the hair has a limited number of ways in responding to varied noxae. Thus, regardless of cause, through the pathogenesis of the lesions, similar changes with considerable dynamics occur and cause diagnostic and genetic counseling dilemmas. For the phenotypic expression of the causative genetic and nongenetic factors, the pathogenesis appears to be the bottleneck and phenotypic similarities and overlap occur. Thus, caution has to be exercised whenever faced with not only trichothiodystrophy but with “ichthyosis” as well. Only longitudinal meticulous observations and repeat testing allow an accurate diagnosis with appropriate prognostications and genetic counseling for patients similar to this patient and the one reported by Przedborski et al. This is particularly pertinent to conditions without diagnostic biochemical and DNA markers.
REFERENCES Kousseff BG, Esterly NB (1988):Trichothiodystrophy, IBIDS Syndrome or Tay Syndrome? Birth Defects: Original Article Series 24(2):169-181,1990. McKusick VA (1990):Mendelian inheritance in man. “Catalogs of Autosomal Dominant, Autosomal Recessive, and X-linked phenotypes,” 9th edition. Baltimore: The Johns Hopkins University Press. Price VH, Odom RB, Ward WH, Jones FT (1980):Trichothiodystrophy: Sulfur-deficient brittle hair as a marker for a neuroectodermal symptom complex. Arch Dermatol 116:1375-1384. Przedborski S, Ferster A, Goldman S, Wolter R, Song M, Tprnnesen ‘T, Pollitt RJ, Vamos E (1990):Trichothiodystrophy, mental retardation, short stature, ataxia, and gonadal dysfunction in three Moroccan siblings. Am J Med Genet 35566-573. Tay C H (1971):Ichthyosiform erythroderma, hair shaft abnormalities, and mental and growth retardation. Arch Dermatol 104:4-13.
Boris G. Kousseff Department of Pediatrics University of S. Florida Tampa, Florida
