Hypochondroplasia and developmental delay

[Guest guest]

This is a message that I received from Dee , who coordinates the LPA

Medical Advisory Board. It was written by Dr. Bellus, an MAB member.

-- Dan

>

> The association of hypochondroplasia and mental retardation has been

> suggested but has never been proven. Some of the initial reports

> describing hypochondroplasia, distinquishing it from achondroplasia,

> suggested that individuals with hypochondroplasia tended to have

> diminished mental capacities. Others claimed that they detected no

> significant mental or developmental problems in patients with

> hypochondroplasia. This association has never been analyzed by a

> formal study.

>

> Drs. Art Aylworth, Thad , Blanton and myself have collected

> some preliminary data pertaining to this point in our study regarding

> genotype-phenotype correlations in hypochondroplasia. We studied

> about 300 patients with suspected diagnoses of hypochondroplasia and

> performed genetic testing to determine whether they carried the common

> FGFR3 mutation (N540K) associated with hypochondroplasia. About half

> the patients had these mutations and half did not. We asked patients

> and families to fill out a short questionaire regarding their medical

> history. Included in this questionaire were a few basic questions

> about whether there was any history of learning disabilities,

> developmental delay, mental retardation or neurological problems.

> About one half of the patients with FGFR3 mutations and about one half

> without FGFR3 mutations reported some type of problem in this area.

> The most commonly listed problems were speech delays and unspecified

> developmental delays. This is much higher than one would expect in a

> population of randomly selected children and young adults.

>

> What can be concluded from our results? First, one must be cautious

> in overinterpreting these results because of the way the data was

> collected. We were mostly relying on subjective reporting by parents

> regarding their child's development. This can be subject to over or

> under estimation of actual developmental achievement. We have not

> performed formal developmental evaluations on individuals in our study

> to determine the actual extent or severity of developmental

> impairment, nor have we compared them to a similar group of

> individuals with achondroplasia or other skeletal dysplasias not

> thought to be associated with developmental delay. All we can say is

> that about 50% of patients with hypochondroplasia (whether or not

> caused by a mutation in the FGFR3 gene) are thought to have some

> delays as reported by their families and that this number is higher

> than one would expect.

>

> It is important to point out that not all individuals with

> hypochondroplasia have developmental delays and some appear to have no

> deficits at all. Therefore, one cannot conclude that having

> hypochondroplasia implies that one is slow or mentally retarded.

> However, one should be alert to the possibility that some individuals

> with hypochondroplasia may have issues related to deficiencies in

> cognitive mental functioning.

>

> So what should be done? Clearly, formal studies using standardized

> developmental evaluations need to be performed on patients with

> diagnoses of hypochondroplasia. Genetic testing should also be

> performed to confirm the presence of the N540K FGFR3 mutation.

> Because early interventions are extremely important in children with

> developmental delays, developmental milestones should be monitored

> carefully in children with suspected diagnoses of hypochondroplasia

> and interventions begun should signs of developmental delay are

> discovered. Once these studies are completed we should be able to

> better assess the association of hypochonroplasia and cognitive

> developmental delay.

>

> I hope this helps and would be happy to answer any further questions

> regarding our study or this matter.

>

> Yours truly,

> Bellus

>

> A. Bellus, M.D., Ph.D.

> Assistant Professor of Genetics & Dermatology

> Dept. Medical & Molecular Genetics

> Indiana University School of Medicine