Hypotrichosis, lymphedema of the legs and acral telangiectasias - new syndrome?

ARTICLE

Lymphedema of the legs combined with hair abnormalities can be a prominent feature of Noonan syndrome (MIM 163950). This phenotype has previously been referred to as "male Turner syndrome" because of the similarities with Turner (45,X0) syndrome. The most prominent characteristics are short stature, webbed neck, triangular facies and sparse, sometimes woolly or fragile hair. Congenital heart disorders can also be a part of the phenotype as can the skin disorder ulerythema ophryogenes. If the latter anomalies dominate the phenotype, it is called cardio-facio-cutaneous syndrome (CFC, MIM 115150). Noonan and CFC syndrome are obviously allelic [1].

Here we describe a girl of Turkish descent suffering from a combination of symptoms that bears some resemblance to Noonan/CFC syndrome but seems sufficiently distinct to warrant description as a separate entity.

Case report

History

The patient, a 12 year-old female, is the first child of consanguineous (first cousins) Turkish parents (Fig. 1). A younger sib is healthy. At the age of four years, swelling of the lower legs appeared. Initially, only the left leg was affected. Exercise apparently aggravated the swelling. Later, reddish papules and maculae developed on the hands and feet. The scalp hair had always been thin and did not grow well. Eyebrows had always been sparse and eyelashes had never been present.

The swelling of the legs was treated with compressive stockings, reportedly with satisfactory results. There were no other complaints and development was apparently normal. Elsewhere, a diagnosis of Klippel-Trenaunay syndrome had been made and the patient was referred to our department for further evaluation at the age of 12 years.

Physical examination

Upon examination, both lower legs appeared swollen with a puffy aspect. The swelling was due to a non-pitting oedema with moderate induration of the skin. Palpation was not painful. The palms and soles showed multiple telangiectasias that emptied when compressed and cutis marmorata-like lividity of the skin (Fig. 2). On several toes, small dark-red papular lesions resembling angiomas were seen (Fig. 3). These, too, could be emptied with compression. Some toes appeared erythematous. A receding frontal hairline was noted, with thinly implanted though normal appearing hair. Exclamation mark hairs were not seen. Eyebrows and eyelashes were missing; pubic and axillary hair growth was scant (Fig. 4). There was a slight mongoloid slant of the eyes. Nails and teeth appeared normal and physical examination did not reveal other abnormalities, particularly no cardiac murmurs, short stature, hyperkeratotic skin lesions or pigmentary abnormalities.

A paediatric evaluation revealed no abnormalities other than those described above. Skin biopsy was refused.

Discussion

The combination of lymphedema and sparse hair is found in the cardio-facio-cutaneous syndrome. This disorder, that is most likely identical to Noonan syndrome [1], is characterised by abnormal (i.e., fine and sparse) hair, hyperkeratotic skin lesions, typical face, short stature, lymphedema and cardiac defects [2]. The symptoms found in our patient show some overlap with CFC syndrome. However, cardiac defects were not found in our patient. Hyperkeratotic lesions or pigmentary abnormalities such as café au lait maculae are not present and neither are overt facial abnormalities. The growth deficiency that almost invariably occurs in CFC/Noonan syndrome [3] is absent as well. Finally, the telangiectasias, angioma-like lesions and cutis marmorata-like skin lividity involving the acral areas are not part of CFC/Noonan syndrome. Klippel-Trenaunay syndrome was considered as an explanation for the lymphedema but deemed less likely because large teleangiectatic nevi and overgrowth of limbs were lacking [4].

The hypotrichosis had been present for as long as the patient could remember. Eyelashes had never been present and the eyebrows had always been thinly implanted. The scalp hair did not grow well. There had been no episodes of accelerated hair loss. Considering this history, alopecia areata as an explanation for the hypotrichosis seems unlikely and congenital hypotrichosis a more appropriate diagnosis. The diffuse pattern and the receded frontal hair line support this notion.

The lesions on the toes bear some resemblance to lymphangiectases in the context of lymphedema. Other skin signs of lymphedema were missing, however, and the lesions were red as opposed to purple, as lymphangiectases usually are. Moreover, they could be emptied using manual pressure. For these reasons we diagnosed the lesions as angiomata.

CONCLUSION

In conclusion, we feel that the phenotype we describe here is distinct from CFC/Noonan syndrome despite having overlapping features. We propose that it is a new entity for which we propose the name hypotrichosis-lymphedema-telangiectasia syndrome.

Acknowledgements

M.A.M. van Steensel is supported by grants from the Dutch Organisation for Scientific Research (NOW grant 920-05-083) and Rebirth SA, Luxembourg.

REFERENCES

1. Leichtman LG. Are cardio-facio-cutaneous syndrome and Noonan syndrome distinct? A case of CFC offspring of a mother with Noonan syndrome. Clin Dysmorphol 1996; 5: 61-4.

2. Reynolds JF, Neri G, Herrmann JP, Blumberg B, Coldwell JG, Miles PV, Opitz JM. New multiple congenital anomalies/mental retardation syndrome with cardio-facio-cutaneous involvement-the CFC syndrome. Am J Med Genet 1986; 25: 413-27.

3. Opitz JM. The Noonan syndrome. Am J Med Genet 1985; 4: 333-43.

4. Samuel M, Spitz L. Klippel-Trenaunay syndrome: clinical features, complications and management in children. Br J Surg 1995; 82: 757-61.