Brief cfinical and laboratory observations
Mehrlingsgeburten beim Menschen, Arch Ges Physiol 88:346, 1901. 5. Myrianthopuolos NC: An epidemiologic survey of twins in a large, prospectivelystudied population, Am J Hum Genet 22:611, 1970. 6. Stockard CR: Developmental rate and structural expres-
Aberrant scalp hair patterning in
hypohidrotic ectodermal dysplasia David W. Smith, M.D.,* and Robert W. Knudson, M.D., Seattle, Wash.
THE PURPOSE of this paper is to report the findings of aberrant directional patterning of scalp hair and its possible relevance in patients with hypohidrotic ectodermal dysplasia. METHODS Patients with HED were evaluated for directional patterning of the scalp hair. These included four personally examined unrelated boys with X-linked HED and four other patients with this disorder,'-' two patients with autosomal recessive HED,:'. '~ and one with yet another variety of HED in which normal dentition and cataracts are features5 None of the patients had any abnormality of brain size and/or shape as judged by appearance and/or measurements. RESULTS Each of the four patients with X-linked HED examined by us had a frontal upsweep of the scalp hair as shown in Fig. 1 and summarized in Table I. Mild-to-moderate From the Dysmorphology Unit, Department of Pediatrics, University of Washington School of Medicine. Supported by Bureau of Community Health Services, Health Services Administration, Public Health Service, Department of Health, Education & Welfare, Project 913; National Institutes of Health Grant No. HD 05961; and Public Health Service Grant No. GM 15253. *Reprint address: Dept. of Pediatrics, RR234 Health Sciences RD-20, University of Washington School of Medicine, Seattle, WA 98195.
The Journal of Pediatrics February 1977
sion: An experimental study of twins, "double monsters" and single deformities, and the interaction among embryonic organs during their origin and development, Am J Anat 28:115-277, 1921. Bulmer MG: The biology of twinning in man, Oxford, 1970, Clarendon Press.
Table I Aberrant scalp hair directional patterning Hypohidrotic ectodermal dysplasia X-linked type Personal cases Literature' -~ Autosomal recessive type:' '; Freire-Maia type; Total
Marked frontal upsweep
4/4 4/4 2/2 1/ 1 11/11
2/2* ? ? ? 2/2
*Only two of the four patients were examined for whorls.
anterior upsweep (commonly termed "cowlick") was noted as a feature in 4.8% of 502 normal children aged 5 to 18 years, but in none was the degree of upsweep as pronounced as in the patients with HED. Two of the patients with X-linked HED also had multiple scalp hair whorls in unusual locations; there was a total of 5 whorls for one of them. The normal frequency of 2 scalp hair whorls is 5%:' Anterior upsweep of the scalp hair was also noted in the HED patients for whom this feature could be assessed adequately from the literature (Table I and Fig. 2). Abbreviation used HED: hypohidrotic ectodermal dysplasia DISCUSSION Directional patterning of scalp hair is secondary to the direction of growth stretch on the skin during the period of downward growth of the hair follicles, from 11 to 16 weeks of fetal life. ~ ~' As the hair follicles are growing downward they come to have a sloping angulation which is related to the direction of growth stretch on the surface of the skin. The normal forces which determine the direction of growth stretch on the scalp skin relate predominantly to the growth and shape of the underlying brain during the period of hair follicle downgrowth. Early defects of brain morphogenesis can secondarily give rise
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Fig. 1. Frontal scalp hair upsweep in a patient with X-linked hypohidrotic ectodermal dysplasia.
to aberrant scalp hair directional patterning and the latter may therefore be utilized as a clue toward the timing of certain problems in brain development?- " The finding of unusual scalp hair patterning in patients with hypohidrotic ectodermal dysplasia, who have normal brain development, implies a second mode of developmental pathogenesis for aberrant scalp hair directional patterning, namely problems in the early morphogenesis of the skin and its derivatives. The finding appears to be a nonspecific one, having been observed in at least three types of HED?-= In summary, aberrant scalp hair patterning may not only be a clue to problems in early brain morphogenesis, but may also constitute a clue to early problems in the morphogenesis of skin and its derivatives, in this instance HED. This feature allows for the early suspicion of such an ectodermal dysplasia. Early detection of H E D may assist in the recognition of hypohidrosis and the attendant risk of excessive hyperthermia. The authors thank Drs. Marian Writ, Ute Ochs, and Vincent Fulginitti for assisting and allowing for the evaluation of HED
Brief clinical and laboratory observations
Fig. 2. Frontal scalp hair upsweep in a girl with autosomal recessive HED. (From Gorlin RJ, and Anderson VE: Z Kinderheilkd 108:1, 1970.)
patients in Anchorage, Alaska, and Tucson, Arizona. We also thank Mrs. Lyle Harrah for research librarian assistance and Ms. Christine Hansen for secretarial assistance. REFERENCES
1. Weech AA: Hereditary ectodermal dysplasia (congenital ectodermal defect). A report of two cases, Am J Dis Child 37:766, 1929. 2. Felsher Z: Hereditary ectodermal dysplasia. Report of a case, with experimental study, Arch Dermatol Syph 49:410, 1944. 3. Niederle J: Anhi drotische ektodermale dysplasia, Monatsschr Kinderheilkd 119:96, 1971. 4. Jaeken J, Emmery L, and Casteels-Van Daele M: Brain damage as a consequence of unrecognised hypohidrotic ectodermal dysplasia, Acta Paediatr Belg 25:241, 1971. 5. Coffin RJ, and Anderson VE: Hypohidrotic ectodermal dysplasia in females. A critical analysis and argument lbr genetic heterogeneity, Z Kinderheilkd 108:1, 1970. 6. Bartlett RC, Eversole LR, and Adkins RS: Autosomal recessive hypohidrotic ectodermal dysplasia: Dental manifestations, Oral Surg 33:736, 1972. 7. Freire-Maia N, Fortes VA, Pereira LC, Opitz JM, Marcallo FA, and Cavalli IJ: A syndrome of hypohidrotic ectodermal dysplasia with normal teeth, peculiar facies, pigmentary
Brief clinical and laborato~ observations
disturbances, psychomotor and growth retardation, bilateral nuclear cataract, and other signs, J Med Genet 12:308, 1975. Smith DW, and Gong BT: Scalp-hair patterning: Its origin
The Journal of Pediatrics February 1977
and significance relative to early brain and upper facial development, Teratotogy 9: t 7, 1974. 9. Smith DW, and Gong BT: Scalp hair patterning as a clue to early fetal brain development, J PEmATR 83:374, 1973.
Proximal 4p-deletion: ehenotype differs from classical 4p-syndrome Uta Francke, M.D.,* La Jolla, Calif., Doralys E. Arias, M.D., Orlando, Fla. and
William L. Nyhan, M.D., Ph.D., La Jolla Calif. PARTIAL DELETION of the short a r m o f c h r o m o s o m e 4 (4p-) is associated with a clinically recognizable syndrome.'-' In these cases, s t a n d a r d c h r o m o s o m e analyses have established that one-third to two-thirds of the short arm of a B group c h r o m o s o m e were deleted. Identification o f c h r o m o s o m e 4 (as c o m p a r e d to the morphologically indistinguishable c h r o m o s o m e 5) was accomplished by autoradiography. C h r o m o s o m e b a n d i n g studies to identify the missing segment with certainty have been reported by Centerwall and associates.' In their patient with the classic 4p- s y n d r o m e the distal half of 4p was deleted. In contrast, the patient reported here, who had quite different and less severe clinical manifestations, has a 4p- kary0type with interstitial deletion of the proximal part of 4p. CASE R E P O R T Patient J.R. was a 30-year-old mentally retarded woman who lived on her own in a protected environment. She had been the 2.190 gm product of an uncomplicated term pregnancy. Fetal movements had been weak. The neonatal period was complicated by poor feeding and pneumonia. Motor and mental development were delayed. She began to walk independently at four years and to use words at three. Menarche occurred at 12 years. Menstrual periods have been regular.
From the Department of Pediatrics, University of California San Diego, School of Medicine, and the Orange Count; Health Department. Supported by United States Public Health Service Grants GM 21110 and GM 17702 and by a grant from the National Foundation-March of Dimes. *Reprint address: Department of Pediatrics, M-O09. UCSD, La Jolla, CA 92093.
Fig. 1. Patient J. R. at 30 years of age. A, Note narrow face, short palpebral fissures, ptosis, prominent nasal bridge, long nose, drooping shoulders. B, Note microcephaly, malformed ear with attached lobe, broad neck.
At four years, she had surgery for a bladder obstruction. At 25 years bilateral sclerostomies were performed for wide-angle glaucoma. At 27 years she suffered spontaneous fractures of metatarsal bones bilaterally. Cervical spine films disclosed a degenerative flexion deformity at C~ and C,~ with no evidence of other osseous abnormalities. On psychometric testing at the age of 30 years, the patient obtained grade equivalents approximately at the fourth-grade level. Strengths were in the areas of reading, general information, responsibility, and socialization, while weaknesses were noted in mathematics and gross motor development. When examined at 30 years, the patient was a well-developed. tall. cooperative woman. Height was 173 cm. span 163 cm, upperto-lower-segment ratio 0.88. The head was symmetrical and small (fronto-occipital circumference = 51 cm; 2 SD < mean). The eyebrows were bushy but not confluent. The glabella was not wide. There was bilateral ptosis (Fig. 1). She had short palpebral fissures (2.5 cm) and a decreased outer canthal distance (8.2 cm), while inner canthal (3.2 cm), interpupillary (5.8 cm), and outer orbital distances (11.5 cm) were at the mean. The right pupil was slightly off-center. Funduscopy revealed a pale, cup-shaped disk on the right and a normal fundus on the left. There was no vision in the right eye and a visual field defect in the left. The nose was long and narrow. The palate was high arched. The lower teeth were sparse and widely spaced. The upper ones had been replaced by a denture. The ears were small, triangular