Clintcal and Experimental Dermatology 1992; 17: 189-191,
Hereditary hypotrichosis (Marie-Unna type) and juvenile macular degeneration (Stargardt's maculopathy) P.MARREN, C.WILSON, R.P.R.DAWBER AND MM.WALSHE*
Department of Dermatolo^,
Stoke Mandeville Hospital, Aylesbury,* Department of Dermatology, Slade Hospital, Oxford Accepted for publication 12 August 1991
Summary Hypotricbosis of the Marie-Unna variety is a distinctive syndrome eponymously named following a publication in 1925 describing a family in wbicb 27 individuals in seven generations were affected by a previously unreporred type of hypotricbosis. Its inheritance is determined by an autosomal dominant gene and it usually occurs as an isolated abnormality. Hereditary macular degeneration (Stargardt's maculopatby) is also well recognized and has been reported in one family in association witb alopecia areata but never in association witb Marie-Unna hypotricbosis. Inberitance of Stargardt's maculopatby is autosomal recessive. Our patient demonstrates tbe co-existence of rbese two uncommon genetic disorders and it would appear tbat both defects bave been independently inberited
scalp bair but cosmetically sbe is less embarrassed by its appearance wbicb looks short and boyisb. Her body hair elsewbere is sparse and wiry. Her eyesight continues to deteriorate and altbougb sbe bas retained some useful peripberal vision ber central vision is now negligible. Sbe was registered blind as a teenager. No other ectodermal abnormalities bave been detected and sbe is of average intelligence. Her brotber, now aged 26 years has generalized abnormal wiry hair but bas experienced minimal scalp alopecia. Ligbt microscopy of rbe proband revealed bairs that were coarse, flattened and twisted at irregular intervals. Electron microscopy (Fig. 1) sbowed longitudinal ridging of tbe hair shafts wirh loss ofthe normal scale pattern and an increa.se in shaft diameter. Similar changes were seen in hair samples taken from the eyebrows, eyelasbes and abdomen. Tbis clinical picture of wiry, coarse twisted hair and tbe very distinctive changes seen on electron microscopy are unique findings in Marie-
Case report The proband patient was tbe eldest daughter of Britisb consanguineous parents. Sbe initially presented at the age of 6 years to an Opbrbalmology Department complaining of blackboard reading difficulties and a gradual deterioration of central vision. Examination revealed reduced visual acuity and macular pigmentary degenerative changes. Similar changes were found in one younger brother aged 4 years, and both children were noted to bave abnormal bair distribution and texture. At referral to a Dermatology department at the age of 8 years, she was found to have extensive alopecia in the occipital and temporal areas with abnt)rmal, coarse, sparsely distributed hair elsewbere on ber scalp. At tbe age of 9 years, ber alopecia extended to involve tbe entire sealp and she felt obliged to wear a wig at scbool for several years. Fortunately, she regrew patcby wiry bair after puberty and sbe has retained tbis since then. Sbe is now in ber late twenties and bas sparse, coarse abnormal Correspondence: Dr Pauline Marren, Department of Dermatology, The, slade Hospital, Headington, Oxford OX3 7JH, UK.
Figure 1. Scanning electronmicrographs of scalp hair showing typically coarse, irregular hair with (a) marked longitudinal ridging (magnification x 275) and (b) twists (magnification x 225), Bars are 01 mm.
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P.MARREN et al.
Figure 2, Fundoscopic appearances showing pigmentary deposition in the region ofthe macula in juvenile macular degeneration.
Unna bypotricbosis and are not found in other clinical settings. Ophtbalmological examination revealed reduced visual acuity witb 6/6 vision in the left eye and 6/36 vision in tbe right eye associated with prominent bilateral central scotomata. Dark adaptation curves, electro-oculograpby and electro-retinograpby were within normal limits but visual evoked responses revealed subnormal values. These investigations togetber with the 'beaten bronze' macular degenerative appearances on fundoscopy support tbe diagnosis of juvenile macular degeneration. (Fig. 2)
Figure 3. Family pedigree outlining the incidence of abnormal hair over three generations suggesting an autosoma! dominant mode of inheritance. ^ proband; • afFected female; O unaffected female; • affected male; D unaffected male; it^ not examined.
Discussion Alopecia or hypotrichosis occurs in a number of bereditary conditions.'"'^ In some, such as pili torti or moniletbrix, a well recognized abnormality of the hair is present. Tbe clinical features seen in the Marie-Unna type of hereditary hypotrichosis are distinctive and have not been associated with any other abnormality.'''^ There is a structural defect ofthe hair shaft with generalized loss of hair which is said to be impossible to confuse with other hereditary hypotrichoses.^ Some family pedigrees have been described all suggesting an autosomal dominant mode of inheritance. Our proband's family pedigree for abnormalities of bair is outlined on Figure 3. Included are two maternal uncles wbo are reputed to have identical wiry sparse bair altbougb tbey were not willing to be
Figure 4. Family pedigree suggesting an autosomal recessive mode of inheritance for juvenile macular degeneration. ^ proband; • affected female; O unaffected female; • affected male; • unaffected male; I' il consanguinity.
JUVENILE MACULAR DEGENERATION AND HYPOTRICHOSIS examined. It supports, however, an autosomal dominant mode of inheritance. Degenerative conditions of the retina, in particular retinitis pigmentosa, have been described in association witb bair'-^ and otber ectodermal abnormalities.''-'" Juvenile macular degeneration or Stargardt's maculopathy is associated with pigmentary abnormalities at the macular area and as a consequence, loss of central vision is an early manifestation. Juvenile macular degeneration has been described in just one family in association with alopecia areata.'' There are no reporrs of Marie-Unna hypotrichosis or other forms of hair dystrophy in association with this form of retinal degeneration. Juvenile macular degeneration is believed to be inherited as an autosomal recessive trait thus more likely to be encountered witb consanguinity. Tbis family pedigree (Fig. 4) also suggests autosomal recessive inheritance for tbis bair abnormality. In tbe proband's generation, tbe same family members bave both abnormalities. In summary we describe tbe co-existence of juvenile macuiar degeneration and bypotricbosis of tbe MarieUnna variety in a family. Botb are well described but uncommon conditions and it would appear that they have been inherited as independent traits. Acknowledgments We would like to acknowledge the assistance of Mr V.Highman ofthe Department of Ophthalmology, Stoke Mandeville Hospital, Aylesbury, Dr M.d'A.Crawfurd of The Kennedy Galton Centre for clinical genetics, Radlett
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Herts, and Dr David Ferguson, Scanning Electron microscopy, Jobn Radcliffe Hospital, Oxford. References 1. HallJCTricho-rhino-phalangeal syndrome type 11. In: Bergsma D, ed. Births Defects Compendium, 2nd edn. London: Macmillan, 1979: 1043. 2. Moynahan EJ. In; Bergsma, D, ed. Birth Defects Compendium, 2nd edn. London: Macmillan, 1979: 723. 3. Reed WB, Lopez DA, Landing B, Clinical spectrum of anhidrotic eetodermal dysplasia. Archives oj' Dermatology 1970; 102: 134— 143. 4. Unna M. Uber Hypotrichosis eongenita hereditaria. Dermatotogische Wochenschrifi 1925; 81: 1167-1178. 5. Peachey RDG, Wells RS. Hereditary hypotriehosis (Marie-Unna Type). Transactions of the St John's Hospital Dermatological Society 1971; 57: 157-166. 6. Stevanovie DV, I lereditary hypotriehosis eongenita: (Marie Unna type), British Journal of Dermatology 1970; 83: 331-337. 7. Bjork A, Jahnberg P. Retinal dystrophy combined with alopecia, Aeta Optithalmotogica 1975; 53: 781-789. 8. Cowan CL Jr, Grimes PE, Chakrabarti S, Minus HR. Kenney. JA Jr. Retinitis Pigmentosa associated with hearing loss, thyroid disease vitiligo and alopecia areata. Retina 1982; 2: 84-88. 9. Parkash H. et al. Eetodermal dysplasia, ectrodactyly and retinitis pigmentosa. Journal of the Indian Dental Association 1983; 55: 355-357. 10. Gregerson E. et at. Ocular abnormalities in Progeria (HutchinsonGilford syndrome). Acta Ophthalmologica 1956; 34: 347-354. 11. Albrectsen B, Svendsen IB. Hypotrichosis, syndactyly and retinal degeneration. Acta Dermato-Venereologica 1965; 36: 96-101, 12. Johnston SS, Darragh J, Nevin NC. Hereditary macular degeneration in three generations of a family. British Journal of Ophthalmology 1973; 57: 578-583.
Hereditary hypotrichosis (Marie-Unna type) and juvenile macular degeneration (Stargardt's maculopathy) P.MARREN, C.WILSON, R.P.R.DAWBER AND MM.WALSHE*
Department of Dermatolo^,
Stoke Mandeville Hospital, Aylesbury,* Department of Dermatology, Slade Hospital, Oxford Accepted for publication 12 August 1991
Summary Hypotricbosis of the Marie-Unna variety is a distinctive syndrome eponymously named following a publication in 1925 describing a family in wbicb 27 individuals in seven generations were affected by a previously unreporred type of hypotricbosis. Its inheritance is determined by an autosomal dominant gene and it usually occurs as an isolated abnormality. Hereditary macular degeneration (Stargardt's maculopatby) is also well recognized and has been reported in one family in association witb alopecia areata but never in association witb Marie-Unna hypotricbosis. Inberitance of Stargardt's maculopatby is autosomal recessive. Our patient demonstrates tbe co-existence of rbese two uncommon genetic disorders and it would appear tbat both defects bave been independently inberited
scalp bair but cosmetically sbe is less embarrassed by its appearance wbicb looks short and boyisb. Her body hair elsewbere is sparse and wiry. Her eyesight continues to deteriorate and altbougb sbe bas retained some useful peripberal vision ber central vision is now negligible. Sbe was registered blind as a teenager. No other ectodermal abnormalities bave been detected and sbe is of average intelligence. Her brotber, now aged 26 years has generalized abnormal wiry hair but bas experienced minimal scalp alopecia. Ligbt microscopy of rbe proband revealed bairs that were coarse, flattened and twisted at irregular intervals. Electron microscopy (Fig. 1) sbowed longitudinal ridging of tbe hair shafts wirh loss ofthe normal scale pattern and an increa.se in shaft diameter. Similar changes were seen in hair samples taken from the eyebrows, eyelasbes and abdomen. Tbis clinical picture of wiry, coarse twisted hair and tbe very distinctive changes seen on electron microscopy are unique findings in Marie-
Case report The proband patient was tbe eldest daughter of Britisb consanguineous parents. Sbe initially presented at the age of 6 years to an Opbrbalmology Department complaining of blackboard reading difficulties and a gradual deterioration of central vision. Examination revealed reduced visual acuity and macular pigmentary degenerative changes. Similar changes were found in one younger brother aged 4 years, and both children were noted to bave abnormal bair distribution and texture. At referral to a Dermatology department at the age of 8 years, she was found to have extensive alopecia in the occipital and temporal areas with abnt)rmal, coarse, sparsely distributed hair elsewbere on ber scalp. At tbe age of 9 years, ber alopecia extended to involve tbe entire sealp and she felt obliged to wear a wig at scbool for several years. Fortunately, she regrew patcby wiry bair after puberty and sbe has retained tbis since then. Sbe is now in ber late twenties and bas sparse, coarse abnormal Correspondence: Dr Pauline Marren, Department of Dermatology, The, slade Hospital, Headington, Oxford OX3 7JH, UK.
Figure 1. Scanning electronmicrographs of scalp hair showing typically coarse, irregular hair with (a) marked longitudinal ridging (magnification x 275) and (b) twists (magnification x 225), Bars are 01 mm.
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P.MARREN et al.
Figure 2, Fundoscopic appearances showing pigmentary deposition in the region ofthe macula in juvenile macular degeneration.
Unna bypotricbosis and are not found in other clinical settings. Ophtbalmological examination revealed reduced visual acuity witb 6/6 vision in the left eye and 6/36 vision in tbe right eye associated with prominent bilateral central scotomata. Dark adaptation curves, electro-oculograpby and electro-retinograpby were within normal limits but visual evoked responses revealed subnormal values. These investigations togetber with the 'beaten bronze' macular degenerative appearances on fundoscopy support tbe diagnosis of juvenile macular degeneration. (Fig. 2)
Figure 3. Family pedigree outlining the incidence of abnormal hair over three generations suggesting an autosoma! dominant mode of inheritance. ^ proband; • afFected female; O unaffected female; • affected male; D unaffected male; it^ not examined.
Discussion Alopecia or hypotrichosis occurs in a number of bereditary conditions.'"'^ In some, such as pili torti or moniletbrix, a well recognized abnormality of the hair is present. Tbe clinical features seen in the Marie-Unna type of hereditary hypotrichosis are distinctive and have not been associated with any other abnormality.'''^ There is a structural defect ofthe hair shaft with generalized loss of hair which is said to be impossible to confuse with other hereditary hypotrichoses.^ Some family pedigrees have been described all suggesting an autosomal dominant mode of inheritance. Our proband's family pedigree for abnormalities of bair is outlined on Figure 3. Included are two maternal uncles wbo are reputed to have identical wiry sparse bair altbougb tbey were not willing to be
Figure 4. Family pedigree suggesting an autosomal recessive mode of inheritance for juvenile macular degeneration. ^ proband; • affected female; O unaffected female; • affected male; • unaffected male; I' il consanguinity.
JUVENILE MACULAR DEGENERATION AND HYPOTRICHOSIS examined. It supports, however, an autosomal dominant mode of inheritance. Degenerative conditions of the retina, in particular retinitis pigmentosa, have been described in association witb bair'-^ and otber ectodermal abnormalities.''-'" Juvenile macular degeneration or Stargardt's maculopathy is associated with pigmentary abnormalities at the macular area and as a consequence, loss of central vision is an early manifestation. Juvenile macular degeneration has been described in just one family in association with alopecia areata.'' There are no reporrs of Marie-Unna hypotrichosis or other forms of hair dystrophy in association with this form of retinal degeneration. Juvenile macular degeneration is believed to be inherited as an autosomal recessive trait thus more likely to be encountered witb consanguinity. Tbis family pedigree (Fig. 4) also suggests autosomal recessive inheritance for tbis bair abnormality. In tbe proband's generation, tbe same family members bave both abnormalities. In summary we describe tbe co-existence of juvenile macuiar degeneration and bypotricbosis of tbe MarieUnna variety in a family. Botb are well described but uncommon conditions and it would appear that they have been inherited as independent traits. Acknowledgments We would like to acknowledge the assistance of Mr V.Highman ofthe Department of Ophthalmology, Stoke Mandeville Hospital, Aylesbury, Dr M.d'A.Crawfurd of The Kennedy Galton Centre for clinical genetics, Radlett
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Herts, and Dr David Ferguson, Scanning Electron microscopy, Jobn Radcliffe Hospital, Oxford. References 1. HallJCTricho-rhino-phalangeal syndrome type 11. In: Bergsma D, ed. Births Defects Compendium, 2nd edn. London: Macmillan, 1979: 1043. 2. Moynahan EJ. In; Bergsma, D, ed. Birth Defects Compendium, 2nd edn. London: Macmillan, 1979: 723. 3. Reed WB, Lopez DA, Landing B, Clinical spectrum of anhidrotic eetodermal dysplasia. Archives oj' Dermatology 1970; 102: 134— 143. 4. Unna M. Uber Hypotrichosis eongenita hereditaria. Dermatotogische Wochenschrifi 1925; 81: 1167-1178. 5. Peachey RDG, Wells RS. Hereditary hypotriehosis (Marie-Unna Type). Transactions of the St John's Hospital Dermatological Society 1971; 57: 157-166. 6. Stevanovie DV, I lereditary hypotriehosis eongenita: (Marie Unna type), British Journal of Dermatology 1970; 83: 331-337. 7. Bjork A, Jahnberg P. Retinal dystrophy combined with alopecia, Aeta Optithalmotogica 1975; 53: 781-789. 8. Cowan CL Jr, Grimes PE, Chakrabarti S, Minus HR. Kenney. JA Jr. Retinitis Pigmentosa associated with hearing loss, thyroid disease vitiligo and alopecia areata. Retina 1982; 2: 84-88. 9. Parkash H. et al. Eetodermal dysplasia, ectrodactyly and retinitis pigmentosa. Journal of the Indian Dental Association 1983; 55: 355-357. 10. Gregerson E. et at. Ocular abnormalities in Progeria (HutchinsonGilford syndrome). Acta Ophthalmologica 1956; 34: 347-354. 11. Albrectsen B, Svendsen IB. Hypotrichosis, syndactyly and retinal degeneration. Acta Dermato-Venereologica 1965; 36: 96-101, 12. Johnston SS, Darragh J, Nevin NC. Hereditary macular degeneration in three generations of a family. British Journal of Ophthalmology 1973; 57: 578-583.
