The status of dermatoglyphics as a biomarker of Tel Hashomer camptodactyly syndrome: a review of the literature

Tel Hashomer camptodactyly (THC) syndrome is a rare disease first termed by Goodman et al. in 1976 after examining two sisters with camptodactyly [1]. Earlier in 1972, they reported two brother and sister pairs having similar clinical features [2]. Up to the present time, a literature search has found only 23 cases. THC is mainly characterized by the presence of camptodactyly with muscular hypoplasia and weakness, skeletal dysplasia, facial dysmorphism (facial asymmetry, small mouth, broad nasal bridge, long philtrum, and hypertelorism), and abnormal dermatoglyphics: Online Mendelian Inheritance in Man® (OMIM) #211960, The portal for rare diseases and orphan drugs (ORPHA) 3292 [3, 4]. In addition, mitral valve prolapse, spina bifida, scoliosis, inguinal hernia, winging scapulae, clubbed feet, syndactyly and clinodactyly were indicated as clinical features [3, 4]. THC is considered to be a disease with autosomal recessive inheritance [5]. Mochizuki et al. [6] recently reviewed the molecular characteristics of a patient described by Toriello et al. in 1990 [7] and suggested that at least several cases of THC may actually be Ehlers–Danlos syndrome.

Goodman et al. [1] stated the importance of dermatoglyphic biomarkers as clinical features when diagnosing THC. Dermatoglyphic characters that need to be present to diagnose THC are: (a) presence of seven or more whorls on digits (these whorls extend beyond the borders of the terminal phalanges), (b) low main line index, caused by the highly vertical orientation of the A to D radiants, and (c) numerous palmar creases that obliterate the normal structure of the ridges and openings of the sweat pores. We systematically analyzed all published cases of THC syndrome to describe the importance of dermatoglyphics in diagnosing this rare disease.

The review has been conducted and reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines [8].

The search of electronic databases yielded 14 publications. In addition, three publications were obtained from gray literature sources and hand searching the reference lists (Fig. 1). Full texts are available for 13 publications [1, 2, 5‐7, 9‐16], only an abstract was available for two publications [17, 18], and an abstract or full text was unavailable for another two [19, 20]. Out of all 17 studies, only 14 publications were reviewed due to the unavailability of records for two publications [19, 20] and one publication reanalyzed a patient whose dermatoglyphics had been described previously [6].

There were 23 cases of THC described in the reviewed publications [6]. Six cases reported from Israel [1, 2, 5], three from Brazil [9, 12], three from India [14, 16], two from Italy [13, 18], three from Poland [10], one from the UK [11], two from the USA [7], two from Russia [17], and one from Hungary [15]. There were 11 females and nine males, and for three patients their sex was not reported in the available abstract [17, 18]. All reported cases were among siblings or first-degree relatives. Eleven cases were born to consanguineous parents [1, 9, 10, 13, 16] while nine were born to non- consanguineous parents [2, 5, 11, 12, 14, 15]. Two cases did not report the consanguinity of their parents [7] and in three cases the consanguinity was not reported in the available abstract [17, 18]. The dermatoglyphics were not reported in one case [16] and for another case dermatoglyphics were not reported in the abstract [18].

Key findings on dermatoglyphic features of the cases of THC are summarized in Table 1.

Of the 21 cases that could be evaluated, eight reported whorls to be the most common digital pattern [1, 2, 7, 12, 15]. Of particular interest, four of these were females with THC syndrome who had at least eight whorls [1, 2, 7, 12]. Conversely, normal males tend to have higher frequencies of whorl patterns [21]. As expected, there were also high average ridge counts, since whorls usually do have more ridges than loops and, of course, arches have zero ridge counts. It is also of interest to note that two of the cases, involving a sister/brother pair, had high frequencies of digital arch patterns with the brother having nine arches [9]. Usually, normal females tend to have more arches than males [21]. Furthermore, there frequently were an increased number of palmar creases than would normally be observed, along with abnormal flexion creases or other palmar dermatoglyphic abnormalities reported in all cases.

The fact that these cases appear to show some unusual results, for instance, in terms of digital patterns from unexpectedly high whorl frequency, especially in females with THC, to a very high number of arches, notably in males with THC, might indicate that there could have been some growth disturbances that took place during early fetal development at the time when epidermal ridges were being formed. In addition, unusual findings with respect to palmar dermatoglyphic features and flexion creases might well be indicative of abnormal developmental conditions. Of course, this intrauterine effect might well have occurred in association with the camptodactyly syndrome. Accordingly, it seems apparent that dermatoglyphic biomarkers may provide important clues when applying differential diagnoses, in conjunction with current molecular testing.

Therefore, it is important to thoroughly observe and record dermatoglyphic features when reporting future patients with THC syndrome, in addition to carrying out modern molecular methods. A highly beneficial consequence of this practice is that possible associations of dermatoglyphic biomarkers in genetically confirmed cases of THC could then be used as a relevant diagnostic aid in countries that have limited medical diagnostic resources.