Estrogen-mediated Height Control in Girls with Marfan Syndrome

This study evaluated the efficacy of a stepwise regimen of estradiol valerate for height control in girls with Marfan syndrome. Eight girls with Marfan syndrome who had completed estrogen treatment for height control were included. Estradiol valerate was started at a dose of 2 mg/day, and then was increased. The projected final height was estimated using the initial height percentile (on a disease-specific growth curve for Korean Marfan syndrome [gcPFHt]), and the initial bone age (baPFHt). After the estrogen treatment, the projected final height was compared to the actual final height (FHt). The median baseline chronological and bone age were 10.0 and 10.5 years, respectively. After a median of 36.5 months of treatment, the median FHt (172.6 cm) was shorter than the median gcPFHt (181.0 cm) and baPFHt (175.9 cm). In the six patients who started treatment before the age of 11 years, the median FHt (171.8 cm) was shorter than the median gcPFHt (181.5 cm) and baPFHt (177.4 cm) after treatment. The median differences between the FHt and gcPFHt and baPFHt were 9.2 and 8.3 cm, respectively. In two patients started treatment after the age of 11, the differences between FHt and gcPFHt, and baPFHt after treatment were -4 and 1.4 cm, and -1.2 and 0 cm for each case, respectively. A stepwise increasing regimen of estradiol valerate may be an effective treatment for height control in girls with Marfan syndrome, especially when started under 11 years old.

Approach to Tall Stature.

As a presenting chief complaint, tall stature represents only ‘tip of iceberg’ of all the tall children. For a pediatrician, it is very important to distinguish familial or constitutional tall stature from other pathological forms of tall stature. For practicing pediatricians, availability of literature discussing clinical approach to a child presenting with tall stature is limited. This article presents clinically simple and rational approach to tall stature.

Tall stature and poor breast development after estrogen replacement in a hypergonadotrophic hypogonadic patient with a 45,X/46,X,der(X) karyotype with SHOX gene overdosage / Estatura alta e hipodesenvolvimento mamário após reposição estrogênica em paciente com hipogonadismo hipergonadotrófico e cariótipo 45,X/46,X, der(X) com superdosagem do gene SHOX

SHOX is exclusively expressed in the developing distal limb bones of human embryos and in the first and second pharyngeal arches. It works as a promoter for linear growth and as a repressor of growth plate fusion. It was reported, recently, that SHOX overdosage and gonadal estrogen deficiency have led to tall stature due to continued growth. We report, in the present study, a female patient with 45,X/46,X, psu idic(X)(pter→q21::q21→pter) karyotype, tall stature, and hypergonadotrophic hypogonadism without Turner stigmas. She did not present breast development even after long term therapy with high estrogen doses. Fluorescence in situ hybridization depicted the presence of three copies of SHOX gene. Microsatellite studies showed paternal origin of der(X). Further studies in similarly affected patients will clarify if the absence of breast development, despite previous high-dose estrogen treatment, is associated to triple copy of SHOX gene.

O gene SHOX é expresso, exclusivamente, no primeiro e no segundo arcos faríngeos, assim como nas extremidades dos ossos dos membros em embriões humanos. SHOX normalmente atua como um promotor para o crescimento linear e como um repressor do fechamento da placa de crescimento. Recentemente, foi descrito que o excesso da proteína SHOX associada à deficiência estrogênica gonadal leva à estatura alta devido ao contínuo crescimento. Neste estudo descrevemos uma paciente do sexo feminino com cariótipo 45,X/46,X,psu idic(X)(pter→q21::q21→pter), estatura alta, hipogonadismo hipergonadotrófico e sem estigmas de Turner. A paciente não apresentou desenvolvimento de mamas, mesmo depois do tratamento prolongado com altas doses de estrógenos. FISH evidenciou a presença de três cópias do SHOX. Estudo de microssatélites demonstrou a origem paterna do der(X). Estudos futuros em pacientes com semelhanças clínicas esclarecerão se a ausência de desenvolvimento de mamas, apesar do tratamento com altas doses de estrógenos, está associada à tripla cópia do SHOX.