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30
patients is unclear. A possible mechanism is endorgan hypersensitivity to androgen. Theoretically, this could lead to increased sebaceous gland secretion and precocious skeletal maturation resulting in premature fusion of the cranial sutures. Although acne vulgaris appears to affect only a certain proportion of the patients, seborrhea may be a consistent feature of Apert's syndrome. The extremely high free fatty acid level in our patient's surface lipid is probably atypical, and we are uncertain of its relevance. REFERENCE Solomon L M, Fretzin D & Pruzansky S (1970) Archives ofDermatology 102, 381
Fig 2 Close-up, showing the severity ofthe skin lesions
Skin and hair very oily. Nearly the entire surface showed comedones, also many papules and pustules (Fig 2). No evidence of excessive virilization. Investigations: Surface lipid studies: Table 1 shows that total lipid production in our patient is more than twice normal and much higher than that of patients with acne vulgaris without Apert's syndrome. Free fatty acid in the surface lipid is also high. Comment The association between Apert's syndrome and acne vulgaris was reported by Solomon et al. (1970). The extensive distribution of the acne in our patient resembles that of Solomon's patients. Because our patient had very oily skin, we were not surprised to find that his surface lipid production level was grossly raised but the extremely high free fatty acid content of his surface lipid was unexpected. We have studied another patient with Apert's syndrome and acne vulgaris. Her acne is less severe, and although she has large numbers of open comedones she has very few inflammatory lesions. Her total lipid production was also greatly elevated (103 ,ug/cm5 in 3 hours) but free fatty acid was within the normal range (17.2 %). The relationship between the seborrhoea, the acne and the skeletal abnormalities in these Table 1 Production of skin surface lipid from the back over a three-hour period Acne
vulgaris (Alpert's) (n=3) 47 Total lipid (sg/cm' in 3 hours) II1 41 AD
Lipid fractions (% of total): Squalene Cholesterol ester Triglyceride Free fatty acid Free cholesterol Unidentified lipid
4.5 4.1
15.8 .42.0 1.9 31.7
5.7 5.1 20.1 32.3 1.5 35.3
Normals (n=8)
5.5 3.4 33.2 20.3 1.7 35.9
Professor M W Greaves: In ordinary acne vulgaris sebum free fatty acids are increased, but only in proportion to the overall increased sebum excretion. An absolute increase in this patient would imply a novel lipolytic abnormality in Apert's syndrome which might shed light on the pathogenesis of acne vulgaris.
Linear Sebaceous N2vi with Convulsions and Mental Retardation (Feuerstein-Mims' Syndrome), Vitamin-D-resistant Rickets Felix S Besser MD DCH (Hospitalfor Sick Children, Great Ormond Street, London WCJ) B B, girl born 21.12.68. Kenyan Asian History: Normal pregnancy and delivery, birth weight 4 lb 13 oz (2.183 kg). No drugs during pregnancy, but a chest X-ray of the mother was carried out during the fourth month. At birth there were extensive nwvi involving scalp, face, back, arms and palms of hands. The child was treated in an oxygen tent for 24 hours. Some difficulty with sucking. By the age of 1 month a floppy head was noted. At 8 months she had a convulsion with a fever. A month later rickets was diagnosed and a year later this was treated with high doses of vitamin D. Subsequently there were more epileptic attacks, which were treated with Epanutin, phenobarbitone and Zarontin. Family history: No consanguinity. The mother had a miscarriage in 1962 but no other pregnancies. On examination: A severely retarded, very floppy child. Extensive sebaceous nmvus affecting scalp, face, neck (Fig 1), front of chest and back. The affected areas on the scalp were bald. The nevus was linear in the midline of the chest. The lesions on the palms of the hands (Fig 3) were a yellowpink colour. Papillomata on lips, angle of mouth and pinni. There was microcephaly and plagio-
31
Section of Dermatology
519
Fig 1 A, linear nevus forehead and anterior chest. Papillomata around mouth. B, left lateral view showing the
nevus involving scalp. Affected areas bald. c, right lateral view. Note bat ear and linear na?vi cheek, scalp and neck cephaly because the scalp measurement at age 7 was 18 inches (46 cm). Bowing of right femur and humerus due to old fractures. Evidence of rickets at wrists and knees. Kyphoscoliosis. Liver and spleen could not be felt. Eyes (Mr K Wybar): Colobomata of right and left irides and of fundus involving optic disc. Pannus on conjunctive. Strabismus.
EEG: Severe abnormality with gross excess of irregular slow activity and multifocal discharges maximal in both anterior frontal regions and inright temporal region. Gross poverty of rhythmic activity appropriate to age. Similar features may be seen in phakomatoses often accompanied by seizures and may be in keeping with multiple cerebral lesions.
11
At
B
C
Fig 2A, bowing offemur with fracture and callus formation. Note decrease in density. B,fracture of humerus with grossly irregular translucent metaphyses. c, fracture offemur. Marked loss of density. D, multiplefractures of humerus and ulna. Epiphyses irregular
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Proc. roy. Soc. Med. Volume 69 July 1976
32 REFERENCES Feuerstein R C & Mims L C (1962) American Journal of Diseases ofChildren 104, 675-679 Marden P M & Venters H D (1966) American Journal of Diseases of Chzildren 112, 79-81 Meythaler H (1975) Klinische Monatsblitter fur Augenheilkunde 166, 244-246 Monahan R H, Hill C W & Venters H D (1967) American Journal ofOphthalmology 64, 529-532 Moynahan E J & Wolff 0 H (1967) British Journal ofDermatology 79, 651 Schimmelpenning G W (1957) Fortschritte aufdem Gebiete der R6ntgenstrahlen und der Nuklearmedizin 87, 716 Tripp J H (1971) Proceedings of the Royal Society ofMedicine 64, 23-24
Fig 3 Lesions involving palm ofright hand in linear distribution
Other investigations: Urine 24-hour excretion of calcium 5.7 mg, phosphorus 52 mg, glucose 99 mg/100 ml. Serum calcium 9.5 mg/100 ml, alkaline phosphatase 156 K-A units, phosphorus 3 mg/100 ml. Urine for reducing substances and organic acids normal. X-rays: Wrist and hand show changes of severe rickets, all bones rarefied. Bone age 2j years. Upper and lower limbs (Fig 2): all bones show marked decrease in density with gross irregular translucent metaphyses and irregular epiphyses. Bowing deformity of long bones; all bones slender. There are multiple healed fractures of long bones. The appearances are those of gross vitamin-D-resistant rickets complicated by epileptic fits. Comment The child has Feuerstein-Mims' syndrome; this disorder belongs to the group of neurocutaneous syndromes (phakomatoses). She also has vitaminD-resistant rickets and multiple fractures. She shows all the features described by Feuerstein & Mims (1962) as well as most reported by Marden & Venters (1966), i.e. failure to thrive, deformities of the skull, colobomata of the iris and choroid. Although bony changes have been described by Moynahan & Wolff (1967) it is not certain if vitamin-D-resistant rickets is part of this syndrome. In the German literature this syndrome is linked with the name of Schimmelpenning (1957) who described a clinical picture similar to that reported by Feuerstein & Mims.
The following cases were also presented: Amyloidosis Cutis Dr Denis Sharvill (Buckland Hospital, Dover) ? Idiopathic Atrophy of Nails. ? Lichen Planus Dr D J Atherton (for Dr P D Samman and Dr R S Wells) (Guy's Hospital, London SE] 9RT) (1) Sjogren's Syndrome and Allergic Vasculitis (2) Cutaneous Polyarteritis Nodosa and Rheumatoid Arthritis Dr P J Marriott (for Dr P F Borrie) (St Bartholomew's Hospital, London ECJ) Annular Granuloma of the Face Dr D D Munro (St Bartholomew's Hospital, London ECI) Secondary Xanthomata Dr J Kirby (for Dr D D Munro) (Edgware General Hospital, Middlesex) Tricho-rhino-phalangeal Syndrome Dr Felix S Besser (Hospitalfor Sick Children, Great Ormond Street, London WCJN3JH) Pemphigus Foliaceus Induced by Penicillamine Dr R A Marsden, Dr A Mowat and Dr H R Vickers (Slade Hospital and Nuffield Orthopadic Hospital, Oxford) Chronic Granulomatous Disease Dr J A Carruthers (for Professor M W Greaves) (St John's Hospitalfor Diseases of the Skin, London WC2) The following short papers were read: Ultrastructural Observations on the Dermo-epidermal Junction Dr R A J Eady (Institute of Dermatology, Homerton Grove, London E9) Androgen Metabolism and Sebaceous Activity in Clonal Acne Dr Mary F Cooper, Dr J B Hay, Dr D McGibbon and Professor S Shuster (University Department of Dermatology, Royal Victoria Infirmary, Newcastle-upon-Tyne, NE] 4LP)
Proc. roy. Soc. Med. Volume 69 July 1976
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patients is unclear. A possible mechanism is endorgan hypersensitivity to androgen. Theoretically, this could lead to increased sebaceous gland secretion and precocious skeletal maturation resulting in premature fusion of the cranial sutures. Although acne vulgaris appears to affect only a certain proportion of the patients, seborrhea may be a consistent feature of Apert's syndrome. The extremely high free fatty acid level in our patient's surface lipid is probably atypical, and we are uncertain of its relevance. REFERENCE Solomon L M, Fretzin D & Pruzansky S (1970) Archives ofDermatology 102, 381
Fig 2 Close-up, showing the severity ofthe skin lesions
Skin and hair very oily. Nearly the entire surface showed comedones, also many papules and pustules (Fig 2). No evidence of excessive virilization. Investigations: Surface lipid studies: Table 1 shows that total lipid production in our patient is more than twice normal and much higher than that of patients with acne vulgaris without Apert's syndrome. Free fatty acid in the surface lipid is also high. Comment The association between Apert's syndrome and acne vulgaris was reported by Solomon et al. (1970). The extensive distribution of the acne in our patient resembles that of Solomon's patients. Because our patient had very oily skin, we were not surprised to find that his surface lipid production level was grossly raised but the extremely high free fatty acid content of his surface lipid was unexpected. We have studied another patient with Apert's syndrome and acne vulgaris. Her acne is less severe, and although she has large numbers of open comedones she has very few inflammatory lesions. Her total lipid production was also greatly elevated (103 ,ug/cm5 in 3 hours) but free fatty acid was within the normal range (17.2 %). The relationship between the seborrhoea, the acne and the skeletal abnormalities in these Table 1 Production of skin surface lipid from the back over a three-hour period Acne
vulgaris (Alpert's) (n=3) 47 Total lipid (sg/cm' in 3 hours) II1 41 AD
Lipid fractions (% of total): Squalene Cholesterol ester Triglyceride Free fatty acid Free cholesterol Unidentified lipid
4.5 4.1
15.8 .42.0 1.9 31.7
5.7 5.1 20.1 32.3 1.5 35.3
Normals (n=8)
5.5 3.4 33.2 20.3 1.7 35.9
Professor M W Greaves: In ordinary acne vulgaris sebum free fatty acids are increased, but only in proportion to the overall increased sebum excretion. An absolute increase in this patient would imply a novel lipolytic abnormality in Apert's syndrome which might shed light on the pathogenesis of acne vulgaris.
Linear Sebaceous N2vi with Convulsions and Mental Retardation (Feuerstein-Mims' Syndrome), Vitamin-D-resistant Rickets Felix S Besser MD DCH (Hospitalfor Sick Children, Great Ormond Street, London WCJ) B B, girl born 21.12.68. Kenyan Asian History: Normal pregnancy and delivery, birth weight 4 lb 13 oz (2.183 kg). No drugs during pregnancy, but a chest X-ray of the mother was carried out during the fourth month. At birth there were extensive nwvi involving scalp, face, back, arms and palms of hands. The child was treated in an oxygen tent for 24 hours. Some difficulty with sucking. By the age of 1 month a floppy head was noted. At 8 months she had a convulsion with a fever. A month later rickets was diagnosed and a year later this was treated with high doses of vitamin D. Subsequently there were more epileptic attacks, which were treated with Epanutin, phenobarbitone and Zarontin. Family history: No consanguinity. The mother had a miscarriage in 1962 but no other pregnancies. On examination: A severely retarded, very floppy child. Extensive sebaceous nmvus affecting scalp, face, neck (Fig 1), front of chest and back. The affected areas on the scalp were bald. The nevus was linear in the midline of the chest. The lesions on the palms of the hands (Fig 3) were a yellowpink colour. Papillomata on lips, angle of mouth and pinni. There was microcephaly and plagio-
31
Section of Dermatology
519
Fig 1 A, linear nevus forehead and anterior chest. Papillomata around mouth. B, left lateral view showing the
nevus involving scalp. Affected areas bald. c, right lateral view. Note bat ear and linear na?vi cheek, scalp and neck cephaly because the scalp measurement at age 7 was 18 inches (46 cm). Bowing of right femur and humerus due to old fractures. Evidence of rickets at wrists and knees. Kyphoscoliosis. Liver and spleen could not be felt. Eyes (Mr K Wybar): Colobomata of right and left irides and of fundus involving optic disc. Pannus on conjunctive. Strabismus.
EEG: Severe abnormality with gross excess of irregular slow activity and multifocal discharges maximal in both anterior frontal regions and inright temporal region. Gross poverty of rhythmic activity appropriate to age. Similar features may be seen in phakomatoses often accompanied by seizures and may be in keeping with multiple cerebral lesions.
11
At
B
C
Fig 2A, bowing offemur with fracture and callus formation. Note decrease in density. B,fracture of humerus with grossly irregular translucent metaphyses. c, fracture offemur. Marked loss of density. D, multiplefractures of humerus and ulna. Epiphyses irregular
520
Proc. roy. Soc. Med. Volume 69 July 1976
32 REFERENCES Feuerstein R C & Mims L C (1962) American Journal of Diseases ofChildren 104, 675-679 Marden P M & Venters H D (1966) American Journal of Diseases of Chzildren 112, 79-81 Meythaler H (1975) Klinische Monatsblitter fur Augenheilkunde 166, 244-246 Monahan R H, Hill C W & Venters H D (1967) American Journal ofOphthalmology 64, 529-532 Moynahan E J & Wolff 0 H (1967) British Journal ofDermatology 79, 651 Schimmelpenning G W (1957) Fortschritte aufdem Gebiete der R6ntgenstrahlen und der Nuklearmedizin 87, 716 Tripp J H (1971) Proceedings of the Royal Society ofMedicine 64, 23-24
Fig 3 Lesions involving palm ofright hand in linear distribution
Other investigations: Urine 24-hour excretion of calcium 5.7 mg, phosphorus 52 mg, glucose 99 mg/100 ml. Serum calcium 9.5 mg/100 ml, alkaline phosphatase 156 K-A units, phosphorus 3 mg/100 ml. Urine for reducing substances and organic acids normal. X-rays: Wrist and hand show changes of severe rickets, all bones rarefied. Bone age 2j years. Upper and lower limbs (Fig 2): all bones show marked decrease in density with gross irregular translucent metaphyses and irregular epiphyses. Bowing deformity of long bones; all bones slender. There are multiple healed fractures of long bones. The appearances are those of gross vitamin-D-resistant rickets complicated by epileptic fits. Comment The child has Feuerstein-Mims' syndrome; this disorder belongs to the group of neurocutaneous syndromes (phakomatoses). She also has vitaminD-resistant rickets and multiple fractures. She shows all the features described by Feuerstein & Mims (1962) as well as most reported by Marden & Venters (1966), i.e. failure to thrive, deformities of the skull, colobomata of the iris and choroid. Although bony changes have been described by Moynahan & Wolff (1967) it is not certain if vitamin-D-resistant rickets is part of this syndrome. In the German literature this syndrome is linked with the name of Schimmelpenning (1957) who described a clinical picture similar to that reported by Feuerstein & Mims.
The following cases were also presented: Amyloidosis Cutis Dr Denis Sharvill (Buckland Hospital, Dover) ? Idiopathic Atrophy of Nails. ? Lichen Planus Dr D J Atherton (for Dr P D Samman and Dr R S Wells) (Guy's Hospital, London SE] 9RT) (1) Sjogren's Syndrome and Allergic Vasculitis (2) Cutaneous Polyarteritis Nodosa and Rheumatoid Arthritis Dr P J Marriott (for Dr P F Borrie) (St Bartholomew's Hospital, London ECJ) Annular Granuloma of the Face Dr D D Munro (St Bartholomew's Hospital, London ECI) Secondary Xanthomata Dr J Kirby (for Dr D D Munro) (Edgware General Hospital, Middlesex) Tricho-rhino-phalangeal Syndrome Dr Felix S Besser (Hospitalfor Sick Children, Great Ormond Street, London WCJN3JH) Pemphigus Foliaceus Induced by Penicillamine Dr R A Marsden, Dr A Mowat and Dr H R Vickers (Slade Hospital and Nuffield Orthopadic Hospital, Oxford) Chronic Granulomatous Disease Dr J A Carruthers (for Professor M W Greaves) (St John's Hospitalfor Diseases of the Skin, London WC2) The following short papers were read: Ultrastructural Observations on the Dermo-epidermal Junction Dr R A J Eady (Institute of Dermatology, Homerton Grove, London E9) Androgen Metabolism and Sebaceous Activity in Clonal Acne Dr Mary F Cooper, Dr J B Hay, Dr D McGibbon and Professor S Shuster (University Department of Dermatology, Royal Victoria Infirmary, Newcastle-upon-Tyne, NE] 4LP)
