Pediatric Dermatology Vol. 9 No. 2 112-1 16
Focal Dermal Hypopl~sia(Goltz Sy~drome): Report of Two Cases with Minor Cutaneous and E x t ~ a ~ ~ t a M n eao~ ~i f~e ~ t a t i ~ n s R. M. Pujol, M.D., J. M. Casanova,* M. Pkrez, X. Matias-Guiu?, M. Pianaguma, and J. M. de Moragas Departments of Dermcrtology and ?Pathology, Hospital de la Sanra Creu i Sant Pau, Barcelona, Spain, and ~ ~ o s ~Arnau i ~ adel V ~ ~ a n oLfaida, ~ a , Spain ~
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Abstract: Two women, ages 33 and 16 years, had focal dermal hypoplasta [Goitz syndrome) with unusual, minimal clinicat ~aR~fes~ations~ The lesions consisted of patchy, atrophic, scaly, telangiectatic macules arranged in a linear pattern along Blaschko’s lines, involving the anterior and laterat aspects of both legs (patient 1) and the anterolateralaspect of the teft leg {patient 2). Type t partial ~ y R ~ ainvolving ~ t ~ the l ~ second and the third toes in both patients was also present. The clinical and histopathologic features and diagnostic difficulties of cases of this disorder with minimal cutaneous and extracutaneous manifestations are discussed. Focal dermal hypoplasia (FDH) (1,2) is an uncommon genodermatosis characterized by a congenital alteration in dermal connective tissue and associated with other defects involving tissues of ectodermal and mesodermat origin. Over 80% of reported cases have involved females, which is probably explained by an X-linked dominant inheritance pattern. Two women had macular, h e a r , atrophic lesions on the lower extremities associated with partial syndactyly . The difficulty in diagnosing patients with minimal cutaneous andlor extracutaneous signs of FDH is discussed. CASE REPORTS
Patient No. 1 A 20-year-old woman came to our department in 1975 for evaluation of a linear, atrophic, macular Address correspondence to J. M. de Moragas, M.D., Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Avda. Sant Antoni M. Claret 167, 08025-Barcelona, Spain.
112
_I___-
_I-
eruption on her legs, a condition present since infancy. Her medical history was unremarkable, and no consanguinity or familial deformities were recorded. Physical e~amina~jon reveaied several atrophic, erythematous, slightly scaly macules following a linear and occasionally cribriform pattern over both legs. The lesions were asymptomatic and extended from the buttocks to the anterior aspects of the feet, being more evident on the anterolateral region. The rest of the physical examination was unremarkable. The patient had sought medical advice from several dermatotogists, but no definitive diagnosis had been established. A skin biopsy was performed, and histopathologic e ~ a ~ i n a of ~ ~a ospecimen n disclosed only an irregular epidermis and a slight broadening of the papillary dermis containing increased numbers of
Pujol et a]: Focal Dermal Hypoplasia
Figure 1. Multiple linear, atrophic, erythematous macules form a cribriform pattern on the anterior aspect of the leg (patient 1).
blood vessels. No dermal foci of fat cells were noted. Given the nonspecific clinical and pathologic features, no definitive diagnosis was made, and the patient was not seen again until January 1989.
Figure 2. Specimen from a biopsy performed in 1989 (patient 1) shows an irregular epidermis with increased numbers of blood vessels. Note the small focus of adipose tissue in the dermis (arrow). (Hematoxylin & eosin; magnification 40x.)
113
During the period from 1975 to 1989 the patient had had three pregnancies, with miscarriages at ages 25 (seventh month of pregnancy) and 29 (second month of pregnancy). In 1984, after a full-term pregnancy, she delivered a girl who had numerous cutaneous and extracutaneous deformities at birth. In January 1989 the patient returned to our department accompanied by her 5-year-old daughter. Physical examination revealed numerous atrophic, erythemato-violaceous macules forming linear or reticulated streaks on the anterior and lateral aspects of both legs (Fig. 1). Several hyperpigmented linear macules in a cribriform pattern were noted on the buttocks and lower back. A partial syndactyly type I involving the second and third left toes was also present. Complete ophthalmologic, odontologic, and radiologic (radiographs of the chest, skull, hands, feet, and examination of the metaphyses of the long bones) surveys were performed and revealed no abnormalities. An additional skin biopsy taken from an atrophic macule on the left leg disclosed only an irregular epidermis with discrete broadening of the papillary dermis with slightly dilated capillaries. Minimal areas of fatty accumulation were observed in the middle and deep dermis (Fig. 2). These histologic features were considered to be nonspecific. The patient's daughter was a 5-year-old with normal intellectual and motor development. Multiple atrophic, erythernatous, cribriform streaks following Blaschko's lines were observed on the trunk and extremities. Several lipomatous nodules were present on the anterior aspect of the right arm and over both knees. Mucosal and intertriginous papillomatous lesions, and dystrophic nails were seen. Dental (malerupted and malplaced teeth) and skeletal (microcephaly, triangular face, hypoplasia of the second right finger) abnormalities were also present. A complete radiologic survey revealed linear, radiopaque densities (osteopathia striata) involving the metaphyses of both femurs and tibias. Histopathologic examination of a skin biopsy specimen from a soft, brownish yellow, nodular, lipomatous lesion on the right knee revealed extreme diminution in the thickness of the dermis, and large, lobulated masses of fat tissue occupying the dermal space. Cutaneous and extracutaneous features permitted us to establish the diagnosis of FDH.
Patient No. 2 An otherwise healthy 16-year-old girl came to our d e p a ~ m e n in t July 1988 for evaluation of linear tel-
114 Pediatric Dermatology Vol. 9 No. 2 June 1992 angiectasias and atrophic macules on the posterolateral aspect of the left leg present since birth. There was no family history of consanguinity, miscarriages, or malformations. Reddish brown, cribriform, atrophic macules were arranged in a linear fashion involving the outer lateral aspect of the left leg (Fig. 3 ) . Discrete, hyperpigmented, atrophic macular lesions were present at the periphery. The eruption started below the left knee and extended downward to the dorsum of the foot. The lesions were asymptomatic, although the patient stated that they became slightly itchy after sun exposure. A partial syndactyly type I involving the second and third left toes was also noted (Fig. 4). The rest of the physical examination was normal. Complementary studies that included complete roentgenographic, ophthalmologic, and odontologic examinations disclosed no abnormalities. Two biopsy specimens taken from skin lesions showed similar histopathologic changes. A discrete acanthosis, with increased numbers of the papillary blood vessels, was observed. The upper dermis did not reveal abnormaIities. A cluster of fat tissue was present in the middermis (Fig. 5 ) .
Figure 4. Partial syndactyly type I involving the second and third lefttoes (patient *).
The diagnosis is usually established on the basis of the classic cutaneous and extracutaneous findings and histoPathologic features*
DISCUSSION
Focal dermal hypoplasia is an uncommon genetic dysplasia of mesodermal and ectodermal tissue, probably transmitted by X-linked dominant inheritance with lethality in hemizygous males (3-15).
Figure 3. ~ribriform,linear, atrophic macules on the anterolateral aspect of the left leg (patient 2).
Figure 5. Irregular epidermis. Small perivascular and per~adnexialclusters of adipose tissue in the middle and deep dermis (patient 2). (Hematoxylin & eosin; magnification 60x.)
Pujol et ai: Focal Dermal Hypoplasia
Atrophic areas in a cribriform or reticulated pattern, lipomatous nodules, aplasia cutis, papillomatous lesions, and nail changes constitute the major dermatologic manifestat~~ns of this disorder. Abnormalities of osseous, ocular, and dental structures are the most frequently encountered extracutaneous features. The genetic background of the syndrome remains poorly understood. The striking preponderance of females, with frequent history of miscarriages and s € ~ ~ ~ suggests b i r ~ h an ~ autosomal ~ X-linked disorder incompatible with survival of affected males. The striate nature of both skin and bone lesions (5,7) has led to the hypothesis that a functional X chromosome mosaicism (Lyon hypothesis) is involved, However, isolated cases of affected males and father-daughter (16) transmission have been reported. Zuffardi et al identified a specific gene locus ~9q32qt)in some cases, with a probable autosomal dominant pattern of inheritance (17). Skin biopsy specimens from characteristic fesions usually reveal a normal epidermis over a markedly hypoplastic dermis. Variable amounts of adipose tissue occupy space in the dermis and in some instances are found close to the epidermis (14). In atrophic lesions, only an irregular epidermis, a broadened papillary dermis, and an increased number of blood vessels could be observed. In advanced lesions the dermis is entirely replaced by fat, and may consist of a narrow remnant directly under the epidermis and around a p ~ e ~ d a g estrucal tures Howell and Freeman (18,191 suggested that accumulations of adipose tissue in FDH result from dysplasia, and not from a focal herniation of subcutaneous fat after dermal hypoplasia. These authors classified the location of the ectopic fat in lesions of FDH into seven patterns. They demonstrated a sequence of abnormal development of fat in the papillary andlor reticular dermis. A slow progression by small aggregates of lipocytes in early lesions may lead to formation of a tumorlike mass after several years. Our two patients displayed a clinical picture that we believe corresponds to FDH with minimal cutaneous and extracutaneous manifestations. We consider that several features in both patients deserve special note. First, the patients had a similar clinical picture: reddish brown, cribriform atrophic skin lesions arranged in a linear fashion on the lower extremities, and unilateral partial syndactyly type I. A second point of interest concerns the diagnostic ~ i ~ ~ u in ~ both t i e cases. s Our first patient exhibI
115
ited signs that were so mild that the diagnosis was not made until she had a child with a typical picture of FDH. In our second patient, the diagnosis is more doubtful, but FDH was suspected on the basis of her clinical appearance and after the finding of small dermal accumulations of fat tissue in skin biopsy specimens. Neither patient had a family history of FDH or classic abnormalities of the disorder. Finally, our cases support the idea that FDH is a ~ e n ~ d e r m athat t ~ ~may ~ s have marked clinical heterogeneity. Several cases of FDH with clinical findings limited entirely to the skin have been reported (4,20), in whom the degree of cutaneous involvement has been variable. In 1988 van der Kerkhof and Happle (21) reported under the label Goltz syndrome without dermal hypoplasia a 24-year-old man with patchy telangiectatic, hypopigmented~and hyperpigmented linear lesions following a nevoid pattern, associated with mu~tipleskin-coiored papules and mild clinodactyiy of both hands. Histopathologic examination disclosed no accum~lat~on of subcutaneous adipose tissue. The authors interpreted this case as FDH syndrome without dermal hypoplasia, and hypothesi~~d that reduced thickness of the dermis is probably not a prerequisite for the diagnosis of this syndrome. Other patients with FDH with minimal cutaneous and extracutaneous manifestations have also been described (16,221. In light of these data, we believe that the diagnosis of FDH should be considered in the presence of linear, atrophic, cutaneous lesions despite the absence of the more classic signs of this disorder. In some patients with rnininial manifestations, a definitive diagnosis cannot be established by clinical or histopathologic criteria alone, and long-term followup seems advisable. Future studies and advances in our knowledge of the specific genetic defect in FDH will probably permit us not only to perform prenatal diagnosis but also establish a definitive diagnosis in some individuals with min~malphenotypic expression. REFERENCES 1. Goltz RW, Peterson WC, Gorlin RJ, Ravits HG. Focal dermal hypoplasia. Arch Dermatol 1962;86:70& 717. 2. Gorlin RJ, Meskin LH,Peterson WC, Goltz RW. Focal dermal hypoplasia syndrome. Acta Dermatovenereol (Stockh) i963;43:421-440. 3. Holden JD, Akers WA. Goltz's syndrome: focal dermal hypoplasia. A combined m e s ~ ~ ~ o dysplad e ~ a ~ sia. Am J Dis Child 1 % 7 ; ~ ~ 4 : ~ ~ ~ - ~ ~ .
116 Pediatric Dermatology Vol. 9 No. 2 June 1992
4. Goltz RW, Henderson RR, Hitch JM, Ott JE. Focal dermal hypoplasia: a review of the literature and report of two cases. Arch Dermatol 1970;101:i-11. 5. Larregue M, Michel V, Maroteaux J, Degos R, Stewart WM. L’hypoplasie dermique en aires, considerations sur l’osteopathie strike et sur le probleme genetique. Ann Dermatol Syph 1971;98:491-500. 6. Ishibashi A, Kurihara Y. Goltz’s syndrome: focal dermal dysplasia syndrome (focal dermal hypoplasia). Dermatologica 1972;144: 156-167. 7. Happle R, Lenz W. Striation of bone in focal dermal hypoplasia: manifestation of functional mosaicism. Br J Dermatol 1977;96:133-138. 8. Cottenot F, Bourgeois-Droin CH, Wallach D, Guetrot D. Hypoplasie dermique en aires associee a une dysplasie fibreuse des 0s. Ann Dermatol Venereol 1979;106: 167-169. 9. Tsuji T. Focal dermal hypoplasia syndrome. An electron microscopical study of the skin lesions. J Cutan Pathol 1982;9:271-281. 10. Stadler JF, Delaire J, David A, Cohen JY, Le Pap6 A. Syndrome de Goltz unilaterale chez un garqon. Ann Dermatol Venereol 1984;l Il:829-830. 11. Malfait Y, Decroix J, Vandaele R, Bourlond A. Un nouveau cas de syndrome de Goltz. Ann Dermatol Venereol 1989;1 16:7 15-7 18. 12. Mallory SB, Krafchik BR. Goltz syndrome. Pediatr Dermatol 1989;6:251-253. 13. Mann M, Wintraub R, Hashimoto K. Focal dermal hypoplasia with an initial inflammatory phase. Pediatr Dermatol 1990;7:278-282. 14. Suskan E, KurkCuoglu N, Uluoglu 0. Focal dermal
15. 16. 17.
18. 19. 20.
21. 22.
hypoplasia (Goltz syndrome) with horseshoe kidney abnormality. Pediatr Dermatol 1990;7:283-286. Goltz RW. Focal dermal hypoplasia. Pediatr Dermato1 1990;7:313-3 14. Burgdorf WHC, Dick GF, Soderberg MD, Goltz RW. Focal dermal hypoplasia in a father and daughter. J Am Acad Dermatol 1981;4:273-277. Zuffardi 0, Caiulo A, Maraschi P, et al. Regional assignment of the loci for adenylate kinase to 9q32 and for 1-acid glycoprotein to 9q31-q32. A locus for Goltz syndrome in region 9q32-qter? Hum Genet 1989;82(1): 17-1 9. Howell JB, Freeman RG. Cutaneous defects of focal dermal hypoplasia: an ectomesodermal dysplasia syndrome. J Cutan Pathol 1989;16:237-258. Freeman RG, Howell JB. Ectomesodermal dysplasia syndrome (focal dermal hypoplasia). Int J Dermatol 1991 ;30:407-408. Pincelli L. Contributo all0 studio delle poichilodermie (a proposito di un caso di poichilodermia congenita a carattere nevico). Arch Ital Dermatol 1957;29: 33-53. Van der Kerkhof PCM, Perret CM, Happle R. GoltzGorlin-Syndrom ohne foikale dermale hypoplasie. Hautarzt 1988;39:743-745. Pizzino D, di Lerma V, Patrizi A, Varoti C. Goltz’s Gorlin syndrome without focal dermal hypoplasia? Dermatology in Europe. Proceedings of the 1st Congress of the European Academy of Dermatology and Venereology, Florence, Italy, 25-26 September 1989. London: Blackwell, 1990:630-631.
Focal Dermal Hypopl~sia(Goltz Sy~drome): Report of Two Cases with Minor Cutaneous and E x t ~ a ~ ~ t a M n eao~ ~i f~e ~ t a t i ~ n s R. M. Pujol, M.D., J. M. Casanova,* M. Pkrez, X. Matias-Guiu?, M. Pianaguma, and J. M. de Moragas Departments of Dermcrtology and ?Pathology, Hospital de la Sanra Creu i Sant Pau, Barcelona, Spain, and ~ ~ o s ~Arnau i ~ adel V ~ ~ a n oLfaida, ~ a , Spain ~
_l_________
~
~
-
_
_
_
_
_
~
-
~
Abstract: Two women, ages 33 and 16 years, had focal dermal hypoplasta [Goitz syndrome) with unusual, minimal clinicat ~aR~fes~ations~ The lesions consisted of patchy, atrophic, scaly, telangiectatic macules arranged in a linear pattern along Blaschko’s lines, involving the anterior and laterat aspects of both legs (patient 1) and the anterolateralaspect of the teft leg {patient 2). Type t partial ~ y R ~ ainvolving ~ t ~ the l ~ second and the third toes in both patients was also present. The clinical and histopathologic features and diagnostic difficulties of cases of this disorder with minimal cutaneous and extracutaneous manifestations are discussed. Focal dermal hypoplasia (FDH) (1,2) is an uncommon genodermatosis characterized by a congenital alteration in dermal connective tissue and associated with other defects involving tissues of ectodermal and mesodermat origin. Over 80% of reported cases have involved females, which is probably explained by an X-linked dominant inheritance pattern. Two women had macular, h e a r , atrophic lesions on the lower extremities associated with partial syndactyly . The difficulty in diagnosing patients with minimal cutaneous andlor extracutaneous signs of FDH is discussed. CASE REPORTS
Patient No. 1 A 20-year-old woman came to our department in 1975 for evaluation of a linear, atrophic, macular Address correspondence to J. M. de Moragas, M.D., Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Avda. Sant Antoni M. Claret 167, 08025-Barcelona, Spain.
112
_I___-
_I-
eruption on her legs, a condition present since infancy. Her medical history was unremarkable, and no consanguinity or familial deformities were recorded. Physical e~amina~jon reveaied several atrophic, erythematous, slightly scaly macules following a linear and occasionally cribriform pattern over both legs. The lesions were asymptomatic and extended from the buttocks to the anterior aspects of the feet, being more evident on the anterolateral region. The rest of the physical examination was unremarkable. The patient had sought medical advice from several dermatotogists, but no definitive diagnosis had been established. A skin biopsy was performed, and histopathologic e ~ a ~ i n a of ~ ~a ospecimen n disclosed only an irregular epidermis and a slight broadening of the papillary dermis containing increased numbers of
Pujol et a]: Focal Dermal Hypoplasia
Figure 1. Multiple linear, atrophic, erythematous macules form a cribriform pattern on the anterior aspect of the leg (patient 1).
blood vessels. No dermal foci of fat cells were noted. Given the nonspecific clinical and pathologic features, no definitive diagnosis was made, and the patient was not seen again until January 1989.
Figure 2. Specimen from a biopsy performed in 1989 (patient 1) shows an irregular epidermis with increased numbers of blood vessels. Note the small focus of adipose tissue in the dermis (arrow). (Hematoxylin & eosin; magnification 40x.)
113
During the period from 1975 to 1989 the patient had had three pregnancies, with miscarriages at ages 25 (seventh month of pregnancy) and 29 (second month of pregnancy). In 1984, after a full-term pregnancy, she delivered a girl who had numerous cutaneous and extracutaneous deformities at birth. In January 1989 the patient returned to our department accompanied by her 5-year-old daughter. Physical examination revealed numerous atrophic, erythemato-violaceous macules forming linear or reticulated streaks on the anterior and lateral aspects of both legs (Fig. 1). Several hyperpigmented linear macules in a cribriform pattern were noted on the buttocks and lower back. A partial syndactyly type I involving the second and third left toes was also present. Complete ophthalmologic, odontologic, and radiologic (radiographs of the chest, skull, hands, feet, and examination of the metaphyses of the long bones) surveys were performed and revealed no abnormalities. An additional skin biopsy taken from an atrophic macule on the left leg disclosed only an irregular epidermis with discrete broadening of the papillary dermis with slightly dilated capillaries. Minimal areas of fatty accumulation were observed in the middle and deep dermis (Fig. 2). These histologic features were considered to be nonspecific. The patient's daughter was a 5-year-old with normal intellectual and motor development. Multiple atrophic, erythernatous, cribriform streaks following Blaschko's lines were observed on the trunk and extremities. Several lipomatous nodules were present on the anterior aspect of the right arm and over both knees. Mucosal and intertriginous papillomatous lesions, and dystrophic nails were seen. Dental (malerupted and malplaced teeth) and skeletal (microcephaly, triangular face, hypoplasia of the second right finger) abnormalities were also present. A complete radiologic survey revealed linear, radiopaque densities (osteopathia striata) involving the metaphyses of both femurs and tibias. Histopathologic examination of a skin biopsy specimen from a soft, brownish yellow, nodular, lipomatous lesion on the right knee revealed extreme diminution in the thickness of the dermis, and large, lobulated masses of fat tissue occupying the dermal space. Cutaneous and extracutaneous features permitted us to establish the diagnosis of FDH.
Patient No. 2 An otherwise healthy 16-year-old girl came to our d e p a ~ m e n in t July 1988 for evaluation of linear tel-
114 Pediatric Dermatology Vol. 9 No. 2 June 1992 angiectasias and atrophic macules on the posterolateral aspect of the left leg present since birth. There was no family history of consanguinity, miscarriages, or malformations. Reddish brown, cribriform, atrophic macules were arranged in a linear fashion involving the outer lateral aspect of the left leg (Fig. 3 ) . Discrete, hyperpigmented, atrophic macular lesions were present at the periphery. The eruption started below the left knee and extended downward to the dorsum of the foot. The lesions were asymptomatic, although the patient stated that they became slightly itchy after sun exposure. A partial syndactyly type I involving the second and third left toes was also noted (Fig. 4). The rest of the physical examination was normal. Complementary studies that included complete roentgenographic, ophthalmologic, and odontologic examinations disclosed no abnormalities. Two biopsy specimens taken from skin lesions showed similar histopathologic changes. A discrete acanthosis, with increased numbers of the papillary blood vessels, was observed. The upper dermis did not reveal abnormaIities. A cluster of fat tissue was present in the middermis (Fig. 5 ) .
Figure 4. Partial syndactyly type I involving the second and third lefttoes (patient *).
The diagnosis is usually established on the basis of the classic cutaneous and extracutaneous findings and histoPathologic features*
DISCUSSION
Focal dermal hypoplasia is an uncommon genetic dysplasia of mesodermal and ectodermal tissue, probably transmitted by X-linked dominant inheritance with lethality in hemizygous males (3-15).
Figure 3. ~ribriform,linear, atrophic macules on the anterolateral aspect of the left leg (patient 2).
Figure 5. Irregular epidermis. Small perivascular and per~adnexialclusters of adipose tissue in the middle and deep dermis (patient 2). (Hematoxylin & eosin; magnification 60x.)
Pujol et ai: Focal Dermal Hypoplasia
Atrophic areas in a cribriform or reticulated pattern, lipomatous nodules, aplasia cutis, papillomatous lesions, and nail changes constitute the major dermatologic manifestat~~ns of this disorder. Abnormalities of osseous, ocular, and dental structures are the most frequently encountered extracutaneous features. The genetic background of the syndrome remains poorly understood. The striking preponderance of females, with frequent history of miscarriages and s € ~ ~ ~ suggests b i r ~ h an ~ autosomal ~ X-linked disorder incompatible with survival of affected males. The striate nature of both skin and bone lesions (5,7) has led to the hypothesis that a functional X chromosome mosaicism (Lyon hypothesis) is involved, However, isolated cases of affected males and father-daughter (16) transmission have been reported. Zuffardi et al identified a specific gene locus ~9q32qt)in some cases, with a probable autosomal dominant pattern of inheritance (17). Skin biopsy specimens from characteristic fesions usually reveal a normal epidermis over a markedly hypoplastic dermis. Variable amounts of adipose tissue occupy space in the dermis and in some instances are found close to the epidermis (14). In atrophic lesions, only an irregular epidermis, a broadened papillary dermis, and an increased number of blood vessels could be observed. In advanced lesions the dermis is entirely replaced by fat, and may consist of a narrow remnant directly under the epidermis and around a p ~ e ~ d a g estrucal tures Howell and Freeman (18,191 suggested that accumulations of adipose tissue in FDH result from dysplasia, and not from a focal herniation of subcutaneous fat after dermal hypoplasia. These authors classified the location of the ectopic fat in lesions of FDH into seven patterns. They demonstrated a sequence of abnormal development of fat in the papillary andlor reticular dermis. A slow progression by small aggregates of lipocytes in early lesions may lead to formation of a tumorlike mass after several years. Our two patients displayed a clinical picture that we believe corresponds to FDH with minimal cutaneous and extracutaneous manifestations. We consider that several features in both patients deserve special note. First, the patients had a similar clinical picture: reddish brown, cribriform atrophic skin lesions arranged in a linear fashion on the lower extremities, and unilateral partial syndactyly type I. A second point of interest concerns the diagnostic ~ i ~ ~ u in ~ both t i e cases. s Our first patient exhibI
115
ited signs that were so mild that the diagnosis was not made until she had a child with a typical picture of FDH. In our second patient, the diagnosis is more doubtful, but FDH was suspected on the basis of her clinical appearance and after the finding of small dermal accumulations of fat tissue in skin biopsy specimens. Neither patient had a family history of FDH or classic abnormalities of the disorder. Finally, our cases support the idea that FDH is a ~ e n ~ d e r m athat t ~ ~may ~ s have marked clinical heterogeneity. Several cases of FDH with clinical findings limited entirely to the skin have been reported (4,20), in whom the degree of cutaneous involvement has been variable. In 1988 van der Kerkhof and Happle (21) reported under the label Goltz syndrome without dermal hypoplasia a 24-year-old man with patchy telangiectatic, hypopigmented~and hyperpigmented linear lesions following a nevoid pattern, associated with mu~tipleskin-coiored papules and mild clinodactyiy of both hands. Histopathologic examination disclosed no accum~lat~on of subcutaneous adipose tissue. The authors interpreted this case as FDH syndrome without dermal hypoplasia, and hypothesi~~d that reduced thickness of the dermis is probably not a prerequisite for the diagnosis of this syndrome. Other patients with FDH with minimal cutaneous and extracutaneous manifestations have also been described (16,221. In light of these data, we believe that the diagnosis of FDH should be considered in the presence of linear, atrophic, cutaneous lesions despite the absence of the more classic signs of this disorder. In some patients with rnininial manifestations, a definitive diagnosis cannot be established by clinical or histopathologic criteria alone, and long-term followup seems advisable. Future studies and advances in our knowledge of the specific genetic defect in FDH will probably permit us not only to perform prenatal diagnosis but also establish a definitive diagnosis in some individuals with min~malphenotypic expression. REFERENCES 1. Goltz RW, Peterson WC, Gorlin RJ, Ravits HG. Focal dermal hypoplasia. Arch Dermatol 1962;86:70& 717. 2. Gorlin RJ, Meskin LH,Peterson WC, Goltz RW. Focal dermal hypoplasia syndrome. Acta Dermatovenereol (Stockh) i963;43:421-440. 3. Holden JD, Akers WA. Goltz's syndrome: focal dermal hypoplasia. A combined m e s ~ ~ ~ o dysplad e ~ a ~ sia. Am J Dis Child 1 % 7 ; ~ ~ 4 : ~ ~ ~ - ~ ~ .
116 Pediatric Dermatology Vol. 9 No. 2 June 1992
4. Goltz RW, Henderson RR, Hitch JM, Ott JE. Focal dermal hypoplasia: a review of the literature and report of two cases. Arch Dermatol 1970;101:i-11. 5. Larregue M, Michel V, Maroteaux J, Degos R, Stewart WM. L’hypoplasie dermique en aires, considerations sur l’osteopathie strike et sur le probleme genetique. Ann Dermatol Syph 1971;98:491-500. 6. Ishibashi A, Kurihara Y. Goltz’s syndrome: focal dermal dysplasia syndrome (focal dermal hypoplasia). Dermatologica 1972;144: 156-167. 7. Happle R, Lenz W. Striation of bone in focal dermal hypoplasia: manifestation of functional mosaicism. Br J Dermatol 1977;96:133-138. 8. Cottenot F, Bourgeois-Droin CH, Wallach D, Guetrot D. Hypoplasie dermique en aires associee a une dysplasie fibreuse des 0s. Ann Dermatol Venereol 1979;106: 167-169. 9. Tsuji T. Focal dermal hypoplasia syndrome. An electron microscopical study of the skin lesions. J Cutan Pathol 1982;9:271-281. 10. Stadler JF, Delaire J, David A, Cohen JY, Le Pap6 A. Syndrome de Goltz unilaterale chez un garqon. Ann Dermatol Venereol 1984;l Il:829-830. 11. Malfait Y, Decroix J, Vandaele R, Bourlond A. Un nouveau cas de syndrome de Goltz. Ann Dermatol Venereol 1989;1 16:7 15-7 18. 12. Mallory SB, Krafchik BR. Goltz syndrome. Pediatr Dermatol 1989;6:251-253. 13. Mann M, Wintraub R, Hashimoto K. Focal dermal hypoplasia with an initial inflammatory phase. Pediatr Dermatol 1990;7:278-282. 14. Suskan E, KurkCuoglu N, Uluoglu 0. Focal dermal
15. 16. 17.
18. 19. 20.
21. 22.
hypoplasia (Goltz syndrome) with horseshoe kidney abnormality. Pediatr Dermatol 1990;7:283-286. Goltz RW. Focal dermal hypoplasia. Pediatr Dermato1 1990;7:313-3 14. Burgdorf WHC, Dick GF, Soderberg MD, Goltz RW. Focal dermal hypoplasia in a father and daughter. J Am Acad Dermatol 1981;4:273-277. Zuffardi 0, Caiulo A, Maraschi P, et al. Regional assignment of the loci for adenylate kinase to 9q32 and for 1-acid glycoprotein to 9q31-q32. A locus for Goltz syndrome in region 9q32-qter? Hum Genet 1989;82(1): 17-1 9. Howell JB, Freeman RG. Cutaneous defects of focal dermal hypoplasia: an ectomesodermal dysplasia syndrome. J Cutan Pathol 1989;16:237-258. Freeman RG, Howell JB. Ectomesodermal dysplasia syndrome (focal dermal hypoplasia). Int J Dermatol 1991 ;30:407-408. Pincelli L. Contributo all0 studio delle poichilodermie (a proposito di un caso di poichilodermia congenita a carattere nevico). Arch Ital Dermatol 1957;29: 33-53. Van der Kerkhof PCM, Perret CM, Happle R. GoltzGorlin-Syndrom ohne foikale dermale hypoplasie. Hautarzt 1988;39:743-745. Pizzino D, di Lerma V, Patrizi A, Varoti C. Goltz’s Gorlin syndrome without focal dermal hypoplasia? Dermatology in Europe. Proceedings of the 1st Congress of the European Academy of Dermatology and Venereology, Florence, Italy, 25-26 September 1989. London: Blackwell, 1990:630-631.
