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Achondroplasia associated with Down syndrome

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American Journal of Medical Genetics 77:168–169 (1998)
Letter to the Editor
Achondroplasia Associated With Down Syndrome
To the Editor:
The concurrence of two distinct genetic diseases in a
patient provides the opportunity to observe the effects
of these disorders on the ultimate phenotype. Up to
now, the concurrence of achondroplasia and Down syndrome in the same patient has been reported only once
[Sommer and Eaton, 1970]. To this report we would
like to add one additional observation of this extremely
rare association. The peculiarity of this case is related
to the fact that some manifestations of achondroplasia
overlap with those of Down syndrome, such as growth
impairment, flat nasal bridge, abnormal shape of head,
hypotonia in early infancy, and a higher frequency of
conductive hearing loss.
Our patient, the fourth child of Caucasian parents,
was born at 37 weeks of gestation, weighing 1,550 g,
following an uneventful pregnancy. Her length at birth
was 42 cm. Both her father and her mother were 43
years old at the time of her birth. We have followed her
to age 12 years and have had the opportunity to observe the effects of both disorders on her phenotype
(Fig. 1). Skeletal survey showed the findings of typical
achondroplasia. Because of the striking developmental
delay and a spectrum of defects not expected in achondroplasia, a peripheral blood culture was performed
and results of karyotype by G-banding were 47,XX,+21.
An echocardiogram showed a small muscular ventricular septal defect (VSD). At age 4 6/12 years, lateral
radiographs of the upper cervical spine in flexion and
extension were taken, and anteroposterior translation
of the occiput in relation to the atlas and axis was measured. No abnormalities were found. Brainstem electric response audiometry (BERA) performed at age 6
years was normal.
In our patient, the interaction of the two processes
during embryogenesis acted more in the sense of producing simple additivity on the resulting phenotype,
and these effects were more obvious in regard to impairment of growth. Her height at almost all ages plotted more than 2 standard deviations (SD) below the
mean when using a published graph specific for achondroplastic patients [Horton et al., 1978]. At age 9 3/12
years she was 84 cm tall, and this is approximately the
*Correspondence to: Dr. Gerson Carakushansky, Departamento de Pediatria, Instituto de Puericultura e Pediatria Martagão Gesteira da UFRJ, Av. Brigadeiro Trompowsky s/n, Cidade
Universitaria, Rio de Janeiro RJ 21941-590, Brazil.
Received 3 September 1997; Accepted 20 November 1997
© 1998 Wiley-Liss, Inc.
Fig. 1.
Patient at age 12 years. Note rhizomelia and genua varaum.
25th centile for a normal 2-year-old girl. Her head circumference was relatively large and averaged within
+2 SD expected for a female with Down syndrome when
using a standard reference curve for head circumference in females with this syndrome, as provided by
Palmer et al. [1992].
We think that the striking deleterious effect on her
linear growth may have been the result of the interaction of the two disorders. Since her menarche occurred
at age 12 with a height of 101 cm, we are predicting
that her final height will be well below 123 cm, which
is the average height for females with achondroplasia.
We wonder if the co-occurrence of the two disorders
Letter to the Editor
in our patient was just a chance event, made somewhat
more likely because of the advanced parental ages. Certainly the null hypothesis that this arose simply by
chance cannot be rejected.
The mutation rate for achondroplasia has been estimated to be between 1.72–5.57 × 10−5 per 1/25,000 ×
1/1,000 [Orioli et al., 1986], and the prevalence rate
between 0.5–1.5/10,000 births. The risk of fathers who
are age 40 years or older to produce offspring with autosomal diseases due to new mutations is estimated to
be at least 0.3–0.5% [Friedman, 1981], and is similar in
magnitude to the risk of Down syndrome among offspring of 35–40-year-old mothers. Given the approximate prevalences of the two disorders, about 1 in every
25,000,000 individuals should have both disorders
solely by chance (1/25,000 × 1/1,000). Therefore, not
taking into account even the correlation related to parental age, one might expect one such case about every
8 years in the United States alone and comparable
rates elsewhere.
Friedman JM (1981): Genetic disease in the offspring of older fathers.
Obstet Gynecol 57:745–749.
Horton WA, Rotter JI, Rimoin DL, Scott CL, Hall JG (1978): Standard
growth curves for achondroplasia. J Pediatr 93:435–438.
Orioli IM, Castilla EE, Barbosa-Neto JG (1986): The birth prevalence for
the skeletal dysplasias. J Med Genet 23:328–332.
Palmer CGS, Cronk C, Pueschel SM, Wisniewski KE, Laxova R, Crocker
AC, Pauli RM (1992): Head circumference of children with Down syndrome (0–36 months). Am J Med Genet 42:61–67.
Sommer A, Eaton AP (1970): Achondroplasia and Down’s syndrome. J Med
Genet 7:63–66.
Gerson Carakushansky*
Stella Rosembaum
Marcia G. Ribeiro
Evelyn Kahn
Mauri Carakushansky
Departamento de Pediatria
Instituto de Puericultura e Pediatria
Martagão Gesteira da UFRJ
Rio de Janeiro, Brazil
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achondroplasia, associates, syndrome, downs
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