Developmental Disorders of the Lymphatics

An information blog for disorders of the lymphatics. For all articles, please click on "Archives" - Due to spammers, I will no longer allow comments, sorry.

Saturday, November 26, 2005

Microcephaly Chorioretinopathy Syndrome


Microcephaly (head is smaller than normal), chorioretinal dysplasia, retinal fold with microcephaly and microphthalmosmental retardation.

Genetics: Autosomal recessive; indication of X-linkage.

Other indications observed in this disorder include: congenital lymphedema and/ora delay in the maturation of the lymphatic system, lymphedema nails (usually in the toes), coarseness of the hair follicles over the dorsum of the hands and feet. While normal intelligence was the more common pattern, there also have been unusually high incidences of slow learning, mental retardation or attention deficit disorder. Psychomotor development is normal.

The most extensive clinical study was involving 5 members of a Chinese family, involving 4 generations, giving clear indications of familial (male) transmission (Leung 1985).


Alternative titles; symbols



The combination of microcephaly and lymphedema and that of microcephaly and chorioretinopathy (156590) are autosomal dominant traits. There are reports also of autosomal recessive microcephaly with chorioretinopathy (251270); Kozma et al. (1996) reported a possible incidence of autosomal recessive microcephaly-lymphedema. Although microcephaly-lymphedema and microcephaly-chorioretinopathy have been considered 2 separate autosomal dominant entities, Feingold and Bartoshesky (1992) and Angle et al. (1994) each reported on 2 unrelated sporadic cases with microcephaly, lymphedema, and chorioretinal dysplasia. Fryns et al. (1995) reported on another sporadic case with microcephaly, pedal lymphedema, and chorioretinal dysplasia with retinal folds.

In 5 members of 4 generations of a Chinese family, Leung (1985) described the combination of microcephaly and lymphedema. The lymphedema was present at birth or began soon after birth. Intelligence was normal. Male-to-male transmission was observed. Crowe and Dickerman (1986) described congenital lymphedema in association with microcephaly in a young boy and his maternal uncle. The mother, maternal grandmother and a sister of the grandmother had microcephaly. The pattern was consistent with X-linkage but may have been indicative of autosomal recessive inheritance with reduced expression in females; the proband's mother, grandmother, and great aunt were microcephalic. In an accompanying editorial, Opitz (1986) made many useful comments. Congenital lymphedema is frequent and represents delay in the maturation of the lymphatics and delay in clearing of the lymphedema regularly present in the fetus. 'Lymphedema nails,' i.e., white nails, especially in the toes, is a persisting sign. Coarseness of the hair follicles over the dorsum of the hands and feet and first phalanges where edema was present earlier is another sign. Unusual persistence of fetal lymphedema is usually associated with congenital hypotonia which clears faster than the lymphedema. What Opitz (1986) called the 'congenital lymphedema facies' (thick tissues, full cheeks, underdeveloped bridge of nose and supraorbital ridges, thick epicanthal folds, bilateral ptosis with thick lids, and micrognathia) is seen with many syndromes. Lymphedema in the hands causes thick volar tissues and later numerous white lines seen on palm prints and with a magnifying glass. Change in the pattern of hair may be seen in other areas of the body in addition to the nape of the neck, e.g., in the forearms. Leung (1987) emphasized the intellectual normality in these cases.

Jarmas et al. (1981) described 2 brothers with severe microcephaly, microphthalmos, retinal folds, and visual deficit. Their mother was also microcephalic and showed mild mental retardation. Young et al. (1987) reported a retarded boy with microcephaly, microphthalmos, and retinal folds. His mother and sister showed microphthalmos and the sister was also microcephalic. Angle et al. (1994) pointed out that the patients of Jarmas et al. (1981) and Young et al. (1987) had lymphedema in addition to microcephaly and chorioretinal dysplasia.

Feingold and Bartoshesky (1992) described 2 unrelated boys with microcephaly, lymphedema, and chorioretinal changes. They concluded that their patients had the same entity as did the patients reported by Leung (1985) and also those reported by McKusick et al. (1966). This seems unlikely in view of the fact that the patients of Leung (1985) had a dominant disorder and the patients of McKusick et al. (1966) clearly had a recessive disorder (see 251270). They stated that in the patients of McKusick et al. (1966)'no lymphedema or mental retardation was present.' It is true that no lymphedema was present, but mental retardation of fairly profound degree was a striking feature. Angle et al. (1994) presented 2 unrelated boys with microcephaly, lymphedema, and chorioretinal dysplasia. Kozma et al. (1996) described a sister and brother from a nonconsanguineous Saudi family who, in addition to severe microcephaly (without mental retardation) and lymphedema, had attention deficit disorder. One brother was more severely affected, and X-linked dominant inheritance could not be excluded.

Strenge and Froster (1998) described a boy with congenital microcephaly and lymphedema. He also had short stature, a feature that had not been described as part of this syndrome, even though it was present in 1 patient reported by Fryns et al. (1995). Bilateral limb lymphedema with lymphedema toenails was still present at age 2 years. At the age of 4 years, the lymphedema began decreasing. At the age of 8 years, lymphedema was restricted to the surface of the toes and the distal part of both feet. His height was at the 3rd centile; the occipital-frontal circumference was 48 cm (less than 3rd centile). Psychomotor development was normal.

Limwongse et al. (1999) provided follow-up on the family reported by Crowe and Dickerman (1986) which was considered to have the microcephaly-lymphedema syndrome. They found chorioretinal dysplasia with variable visual deficit in multiple relatives, supporting the concept that the combination of microcephaly, lymphedema, and chorioretinopathy constitutes a single autosomal dominant genetic entity with variable expression. In an editorial comment on the report by Crowe and Dickerman (1986), Opitz (1986) suggested that the facial characteristics of their proband at birth and during childhood resembled those of other patients with disorders associated with congenital lymphedema. Limwongse et al. (1999) noted a striking similarity between the facial characteristics of their proband at age 14 years and those of the 11-year-old patient of Sadler and Robinson (1993). Both patients had prominent ears, broad nasal bridge, broad and large nasal tip with anteverted nares, prominent full lips, and pointed chin.


1. Angle, B.; Holgado, S.; Burton, B. K.; Miller, M. T.; Shapiro, M. J.; Opitz, J. M. :
Microcephaly, lymphoedema, and chorioretinal dysplasia: report of two additional cases. Am. J. Med. Genet. 53: 99-101, 1994.PubMed ID :
2. Crowe, C. A.; Dickerman, L. H. :
A genetic association between microcephaly and lymphedema. Am. J. Med. Genet. 24: 131-135, 1986.PubMed ID :
3. Feingold, M.; Bartoshesky, L. :
Microcephaly, lymphedema, and chorioretinal dysplasia: a distinct syndrome? Am. J. Med. Genet. 43: 1030-1031, 1992.PubMed ID :
4. Fryns, J. P.; Smeets, E.; Van den Berghe, H. :
On the nosology of the 'primary true microcephaly, chorioretinal dysplasia, lymphoedema' association. Clin. Genet. 48: 131-133, 1995.PubMed ID :
5. Jarmas, A. L.; Weaver, D. D.; Ellis, F. D.; Davis, A. :
Microcephaly, microphthalmia, falciform retinal folds and blindness. Am. J. Dis. Child. 135: 930-933, 1981.PubMed ID :
6. Kozma, C.; Scribanu, N.; Gersh, E. :
The microcephaly-lymphoedema syndrome: report of an additional family. Clin. Dysmorph. 5: 49-54, 1996.PubMed ID :
7. Leung, A. K. C. :
Dominantly inherited syndrome of microcephaly and congenital lymphedema. Clin. Genet. 27: 611-612, 1985.PubMed ID :
8. Leung, A. K. C. :
Dominantly inherited syndrome of microcephaly and congenital lymphedema with normal intelligence. (Letter) Am. J. Med. Genet. 26: 231 only, 1987.PubMed ID :
9. Limwongse, C.; Wyszynski, R. E.; Dickerman, L. H.; Robin, N. H. :
Microcephaly-lymphedema-chorioretinal dysplasia: a unique genetic syndrome with variable expression and possible characteristic facial appearance. Am. J. Med. Genet. 86: 215-218, 1999.PubMed ID :
10. McKusick, V. A.; Stauffer, M.; Knox, D. L.; Clark, D. B. :
Chorioretinopathy with hereditary microcephaly. Arch. Ophthal. 75: 597-600, 1966.PubMed ID :
11. Opitz, J. M. :
On congenital lymphedema. (Editorial) Am. J. Med. Genet. 24: 127-129, 1986.PubMed ID :
12. Sadler, L. S.; Robinson, L. K. :
Chorioretinal dysplasia-microcephaly-mental retardation syndrome: report of an American family. Am. J. Med. Genet. 47: 65-68, 1993.PubMed ID :

13. Strenge, S.; Froster, U. G. :
Microcephaly-lymphedema syndrome: report of a family with short stature as additional manifestation. Am. J. Med. Genet. 80: 506-509, 1998.PubMed ID :

14. Young, I. D.; Fielder, A. R.; Simpson, K. :
Microcephaly, microphthalmos, and retinal folds: report of a family. J. Med. Genet. 24: 172-184, 1987.PubMed ID :


Victor A. McKusick - updated : 2/10/2000

Victor A. McKusick - updated : 1/15/1999Iosif W. Lurie - updated : 7/26/1996


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