ARTICLE
Hair shaft abnormalities are found in a number of syndromes involving
tissues and organs of ectodermal origin; nails, teeth, sweat glands [1-4].
Some hair shaft abnormalities are pathognomonic for certain diseases;
the most typical example being trichorrhexis invaginata, or bamboo hairs,
which is almost always associated with ichthyosis linearis circumflexa
and atopy in the Netherton syndrome [5, 6].
Pili torti, hairs twisted around their own axis, is another typical
hair shaft abnormality. Seen in isolation without associated findings,
it is often inherited autosomal-dominantly.
Pili torti associated with sensorineural hearing loss was first recognized
and described as a combined finding in 1965 [7]. The patients have variable
degrees of pili torti, the hearing problems vary from deafness to reduced
hearing in defined frequencies.
In this paper, Bjørnstad's original patients were revisited,
and a review of patients with this rare syndrome is given. As a differential
diagnosis of pili torti, a short overview of conditions and syndromes
including pili torti is given.
Methods
All the patients gave their consent to use information about their previous
history. Also, they gave information about their familial history, blood
samples for genetic analyses (which are being prepared at the Department
of Genetics, University of Tromsø, Norway, for a cooperative study
with Professor Seidman at Harvard in Boston), and samples of their scalp
hair for scanning electron microscopical investigation.
It was possible to contact four out of five of Bjørnstad's original
patients with pili torti and hearing loss. The fifth patient was deceased,
and had left no relatives. By going through the familial history thoroughly,
it was possible to get in contact with one brother of one of Bjørnstad's
patients, who had been mentioned in the original paper but not investigated
himself. Also, a female relative of another patient was contacted and
her hair samples investigated for the previous study.
For scanning electron microscopy, the hair samples were fixed onto a
probe with double-sided scotch tape, coated with 30 nm layer of gold/palladium
alloy in a Polaron E 5100 Sputter Coater (Polaron Equipment Ltd., Watford,
UK), and the specimens were then examined and photographed in a Philips
SEM 515 microscope (Philips, Eindhoven, The Netherlands).
Patients (numbers refer
to Table 1)
Patient 1
GB, born in 1936 was seen at the age of nine years. She was the only
child. Since her first year of life the parents had noticed slow hair
growth. In the first years of life, the hair was brittle, short at the
neck (1 cm), on the forehead up to 20 cm. Later in life, the hair was
very short due to increased breakage (Fig.
1a). A 45 dB hearing loss for speech was diagnosed some years
later, and in addition to a wig she has used a hearing device all her
adult life. Her hairs show twisting in the scanning electronmicroscopical
investigation (Fig. 1b).
Patient 2
TK, born 1935, was seen at the age of 20. She had fair hair, that had
been long and dark until the age of one year. The hairs were easily pluckable.
Reduced hearing was diagnosed at the age of three. Urinary excretion of
17-ketosteroids and corticoids was in the lower range of the reference
values. A gynecological examination revealed hypoplasia of the internal
genitalia. Since the age of 15 she had been using a wig and a hearing
aid (Fig. 2a). Her brother,
sister, and two children (a son and a daughter) all have normal hair and
normal hearing. In the scanning electronmicroscopical investigation, the
hairs show both pili torti and pili canaliculi (Fig.
2b).
Patient 3
JS, born 1954, was seen at the age of three. She was the only child,
and had had rough hair since birth (Fig.
3a). In addition to a reduced hearing ability noticed at the age
of six, she has a heterochromia of the hair. She has been using a hearing
aid since the age of seven. Her hair growth has improved over the years,
although she has been using a wig since puberty. The hairs show single
and multiple ridges in the scanning electronmicroscopical investigation
(Fig. 3b).
Patient 4
LB, born 1908, seen at the age of 36. She is the fifth of seven siblings.
One elder brother had been bald since the age of 18. Her hair grows to
the length of five centimeters, and then breaks off (Fig.
4a), typically explained by pili torti, seen in the scanning electronmicroscopical
investigation (Fig. 4b).
On the back of her head the hair may grow to the length of 10-20 cm. Reduced
hearing was diagnosed after an infection with morbilli at the age of seven
years. She is now deceased, and has left no relatives.
Patient 5
AH, born 1944. Hair complaint since his eighth year of life. His hairs
broke off easily and showed marked thinning already at puberty. The hair
was of varying color, from brown to reddish and light gold. He had suffered
from hearing problems since an early age, an audiogram showed bilateral
deafness and hearing loss for speech. He is now bald and was therefore
not able to give any scalp hair samples for the scanning electronmicroscopical
investigation.
Own cases
Patient 34
GH, born 1940, had suffered from increased breakage of hair since childhood,
and hearing loss since puberty. Since the age of 20 he has used a hearing
aid. Clinically, the short hair seems normal, on scanning electron microscopical
investigation, longitudinal ridges and twisted hairs are found.
He is the four years older brother of patient 5 of Bjørnstad's
patients (Fig. 5). Neither
he nor his hairs have been previously investigated.
Patient 35
SK born 1926. Absence of hair since early childhood, almost complete
hearing loss recognized in early childhood. Used a wig and hearing device
since puberty. A scanning electronmicroscopical investigation of hairs
shows grave abnormality, with twisting and ridging of hairs.
She is a female cousin of patient 2 of Bjørnstad's patients (Fig.
6). Neither she nor her hairs have been previously investigated.
Discussion
Schütz was probably the first to describe hairs twisted around
their own axis [8], and in 1922, Riecke described similar findings and
called them trichokinesis [9]. Ormsby and Mitchell presented a patient
with twisted hairs at a dermatological meeting [10]. Galewsky described
two patients with twisted hairs and introduced the term pili torti in
1932 [11]. Ronchese described one patient with the same hair abnormality,
and used the term twisted hairs [12]. Bjørnstad described one patient
with twisted hairs in 1941, the first in Scandinavia [13].
In 1965, Bjørnstad presented 8 patients with pili torti, out
of whom five also suffered from hearing loss for speech [7]. The combination
of these two findings was later coined Bjørnstad's syndrome [14].
An autosomal-recessive mode of inheritance was suggested.
Both the later cases have been consistent with an autosomal-dominant
inheritance, but the majority, including the families seen by Bjørnstad,
seem to be inherited autosomal-recessively. Recently, Lubianca Nero and
co-workers, by investigating the members of a large family of Mexican
origin, demonstrated that the Bjørnstad syndrome gene maps to chromosome
2q34-36 [15]. The family of patient 3 of Bjørnstad's original patients
carries part of the haplotype that was found in the Mexican family (Jon
Seidman, Harvard, personal communication). The other Norwegian families
are presently under investigation.
Including the two presented cases, 35 patients in all (20 female, and
15 male patients) in 21 different families with pili torti and sensorineural
deafness have been described; seven Norwegian, eleven of Mexican origin,
five Dutch, three caucasian American, three German, one Italian, one Portugese,
and four French patients (Table I). In 8 out of the 21 families,
more than one person with pili torti and hearing loss was observed [7,
14-27].
Two brothers reported by Porter [19], and one patient described by van
Buggenhout with Bjørnstad's syndrome [25] also had mental retardation.
Crandall and co-workers described hypogonadism in two out of three male
brothers of Mexican origin with Bjørnstad's syndrome [16]. Reed
and co-workers had previously presented this family [14], however, he
had seen the boys when they were prepubertal, and hence a hypogonadism
was not evident at that time. In Bjønstad's original report, patient
2 had urinary excretion of 17-ketosteroids and corticoids in the lower
range of the reference values, and a gynecological examination revealed
hypoplasia of the internal genitalia.
Thus, mental retardation and hypogonadism may be regarded as associated
signs in patients with sensorineural deafness and pili torti.
Braun-Falco and Landthaler describe one female patient suffering from
congenital deafness combined with pili torti and ichthyosis
vulgaris [27]. Her father suffered from deafness. As ichthyosis vulgaris
is inherited autosomal-dominantly, and pili torti combined with deafness
follows an autosomal-recessive trait, this represents a patient with Bjørnstad's
syndrome who incidentally suffers from ichthyosis vulgaris.
For clinical and anamnestical details of the reported patients with
Bjørnstad's syndrome see Table I.
The classical pili torti as an isolated defect presents in early childhood,
the late manifestation in puberty is referred to as pili torti type Beare
[28]. Twisted hairs combined with other developmental defects has been
reported in various syndromes and conditions [1, 2, 29].
The most important differential diagnosis in pili torti is probably
Menkes' disease [30]. Pili torti, when diagnosed, are indicative for this
condition, and serum copper and serum coeruloplasmine levels should be
determined. Early treatment is vital; if given within the first ten days
of age, parenteral copper-histidine has shown promising results [31, 32].
Many affected boys appear normal in the newborn period, but the first
signs usually begin at 6 to 8 weeks of age, such as seizures followed
by slowing in the rate of developmental progress and physical growth.
The hair is often white or yellow in color, and feels like steel wool.
SEM shows twisting, both in patients and carriers [33]. The lack of copper
causes disturbances in the cross-lining of elastin, which leads to the
pathological changes found in vessels, but also in the connective tissue
leading to cutis laxa [34]. Copper-dependent cross-linking of sulphur
explains the development of pili torti and subsequent increased fragility
of the hairs. Pathoanatomically, there is a cerebral and cerebellar degeneration.
The genetic cause is a mutation in the gene encoding for a protein belonging
to the P-type ATP-ase family of cation transporters [35-37].
Other important syndromes with pili torti include a number of ectodermal
dysplasias.
In 1968, Rapp and Hodgkin [38] described a mother, son, and daughter
with anhidrotic ectodermal dysplasia, cleft lip, and cleft palate. Silengo
et al. [39] reported an affected mother and daughter. The daughter
had pili torti, and coarse and wiry scalp hair. The mother, who was bald,
had had similar hair as a child. Salinas and Montes [40] in addition found
uncombable and wiry hair that progressed to alopecia in adulthood. They
suggested that the characteristic hair change is pili canaliculi, as under
the scanning electron microscope and polarizing microscope, hairs showed
canal-like depressions running the length of the axis.
Brittle, sulphur-deficient hair may also show twisting of the hair shaft
[41]. Trichothiodystrophy appears to represent a pathological feature
associated with several disorders in organs derived from ectoderm and
neuroectoderm [42], and different syndromes can be distinguished; BIDS,
Tay, and PIBIDS syndrome. The hairs show alternating dark and light bands
under polarizing microscopy, trichoschisis, and absent or defective cuticle.
The term trichothiodystrophy was introduced by Price et al. in
1980 [43]. In addition to brittle hair, the patients have brittle nails,
ichthyotic skin, and physical and mental retardation. Approximately half
of the patients display photosensitivity, correlated with a nucleotide
excision repair defect.
Rare conditions which have occasionally been found with pili torti include
acrofacial dysostosis [44], ectodermal dysplasia with cleft lip and palate,
hand and foot deformity, and mental retardation [45], "pure" hair-nail
ectodermal dysplasia [46-48], trichodysplasia-xeroderma [49], pili torti
associated with developmental delay [50], and associated to metabolic
disorders [51, 52].
Finally, acquired pili torti have been reported in scarring alopecia
[53], where the twisted hairs are due to destruction of the follicle,
but also in anorexia nervosa [54]. In the latter case, pili torti may
develop as a result of malnutrition.
CONCLUSION
In conclusion; in cases of peculiar hair in childhood as well as hair
loss in infancy, an investigation for structural abnormalities should
be performed. When diagnosed, pili torti should be followed by a minimum
of further investigations. In addition to examining other ectodermal tissue,
serum-copper, and serum-coeruloplasmin should be determined, and a thorough
auditory test performed.
The combination of different signs, in Bjørnstad's syndrome the
concomitant presence of pili torti and hearing deficits, may and should
lead the clinician to consider possible common pathophysiological or genetic
causes for the observed abnormalities. Family history and analyses of
the pedigree may give clues to the mode of inheritance. Modern molecular
biology is necessary to confirm the common genetic cause of certain diseases
and syndromes. Nevertheless, accurate clinical diagnosis combined with
the awareness of possible new combinations and associations almost always
preceeds the detection of new syndromes, and Bjørnstad's syndrome
is a fine example of the steps leading to a new syndrome.
Acknowledgement
Professor Roar Th Bjørnstad, former Head of the Department of
Dermatology, Ullevål Hospital, University of Oslo, Norway, kindly
gave permission to use photographs of the patients (Figs.
1, 2a, 3a and 4a), and supplied
hair samples from patient 4.
Article accepted on 7/10/99
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