Marfanoid features and X-linked mental retardation associated with craniofacial abnormalities: the Lujan-Fryns syndrome

Aspectos marfanoides e retardo mental ligado ao X associados a anormalidades craniofaciais: síndrome de Lujan-Fryns

LETTERS

Marfanoid features and X-linked mental retardation associated with craniofacial abnormalities: the Lujan-Fryns syndrome

Aspectos marfanoides e retardo mental ligado ao X associados a anormalidades craniofaciais: síndrome de Lujan-Fryns

Paula Macedo Dieckmann; Lara Carneiro de Lucena; Lívia Almeida Dutra; José Luiz Pedroso; Orlando G.P. Barsottini

Department of Neurology, Universidade Federal de São Paulo (Unifesp), São Paulo SP, Brazil

^{Correspondence}

Marfanoid features associated with mental retardation are often a diagnostic challenge for general neurologists, since several genetic and inborn metabolic diseases present this clinical spectrum. Some of these diseases have typical clinical markers that may aid diagnosis. For instance, Lujan-Fryns syndrome is a recessive X-linked condition characterized by mental retardation, marfanoid habitus, and facial dysmorphisms^1,2.

Herein, we described a male patient with marfanoid habitus and mental retardation, in whom the presence of facial dysmorphisms was the clue for diagnosing the Lujan-Fryns syndrome.

CASE REPORT

A 25-year-old man presented to the Division of General Neurology, at Universidade Federal de São Paulo, with developmental delay and learning disabilities since childhood. His family history was unremarkable and there was no parental consanguinity. He had another brother with possible marfanoid features and learning disabilities, and other three ones and a sister that had not been evaluated. A possible X-linked inherited disorder was suspected. On examination, the patient presented high stature, prominent forehead, large nose, deep and short filters, long narrow face, low-set ears, small mandible, long arms and fingers, and hypotonia (Figure). He also showed severe mental retardation. Cardiologic and ophthalmologic evaluations were normal. Brain magnetic resonance resulted normal. His karyotype was 46 XY, and fragile X genetic test was negative. Serum homocysteine was 9.95 mmol/L (normal range from 5 to 15 mmol/L). With this clinical presentation and after exclusion of other diseases, the diagnosis of Lujan-Fryns syndrome was suggested.

DISCUSSION

In 1984, a new form of X-linked mental retardation was described. The so-called Lujan-Fryns syndrome or X-linked mental retardation with marfanoid habitus syndrome is a rare syndromal X-linked form of mental retardation (mild to moderate mental retardation), associated with tall marfanoid stature, distinct facial dysmorphism, and behavioral problems^1,2. Despite known genetic origin, there is no genetic test available to acknowledge the diagnosis of Lujan-Fryns syndrome, though a mutation in MED12 gene has already been described³.

Craniofacial features in Lujan-Fryns syndrome include prominent forehead, long narrow face, maxillary hypoplasia, small mandible, long nose with high and narrow nasal bridge, short and deep philtra, thin upper lip, highly arched palate, receding chin, and low-set retroverted normal shaped ears⁴. In some cases, brain imaging shows corpus callosum agenesis⁴.

The diagnosis of Lujan-Fryns syndrome is based on clinical manifestations and on exclusion of other conditions, such as homocystinuria, Fragile X syndrome, 22q11 deletion syndrome, Klinefelter and Marfan syndromes. Opitz-Kaveggia syndrome is an allelic disorder with an overlapping phenotype. It should also be remembered as a differential diagnosis of schizophrenia, considering the important behavioral problems associated with that condition (hyperactiveness, aggressiveness, and autistic-like behavior). There is no available treatment for this syndrome. In general, patients need special education and psychological support. Genetic counseling is recommended, considering transmission pattern of the syndrome^3,4.

In summary, our report reinforces craniofacial features as a clue for the diagnosis of Lujan-Fryns syndrome in the context of marfanoid habitus and possible X-linked mental retardation.

Conflict of interest:

There is no conflict of interest to declare.

Received 01 April 2012

Received in final form 28 June 2012

Accepted 07 July 2012

• 1. Lujan JE, Carlin ME, Lubs HA. A form of X-linked mental retardation with marfanoid habitus. Am J Med Genet 1984;17:311-322.
• 2. Fryns JP, Buttiens M. X-linked mental retardation with marfanoid habitus. Am J Med Genet 1987;28:267-274.
• 3. Schwartz CE, Tarpey PS, Lubs HA, et al. The original Lujan syndrome family has a novel missense mutation (p.N1007S) in the MED12 gene. J Med Genet 2007;44:472-477.
• 4. Van Buggenhout G, Fryns JP. Lujan-Fryns syndrome (mental retardation, X-linked, marfanoid habitus). Orphanet J Rare Dis 2006;1:26.

Publication Dates

• Publication in this collection
  16 Jan 2013
• Date of issue
  Jan 2013