Case Report: Improved Height in a Patient With Myhre Syndrome Using a Combination of Growth Hormone and Letrozole

Myhre syndrome is a rare disorder caused by a heterozygous mutation in the SMAD4 gene. Affected patients may exhibit dysmorphic facial features, intrauterine growth retardation, short stature, obesity, muscle hypertrophy, thickened skin, limited joint movement, hearing impairment, and varying degrees of psychomotor developmental disorder. Serious complications of the cardiovascular and respiratory system may be seen later in life. We report the case of a Chinese boy with Myhre syndrome presenting with a novel symptom of giant testicles where treatment with growth hormone combined with letrozole successfully improved his short stature. This case shows that letrozole combined with growth hormone can improve height in children with Myhre syndrome without adverse effects.

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Growth hormone treatment for short stature in children with intrauterine growth retardation

10.1002/14651858.cd006293.pub2 ◽

2009 ◽

Author(s):

Hui Ming Yang ◽

Meng Mao ◽

Chao Min Wan ◽

Fan Yang

Keyword(s):

Growth Hormone ◽

Short Stature ◽

Growth Retardation ◽

Intrauterine Growth Retardation ◽

Growth Hormone Treatment ◽

Hormone Treatment ◽

Intrauterine Growth

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Mutation at Cleavage Site of Insulin-Like Growth Factor Receptor in a Short-Stature Child Born with Intrauterine Growth Retardation

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2004-1947 ◽

2005 ◽

Vol 90 (8) ◽

pp. 4679-4687 ◽

Cited By ~ 84

Author(s):

Yuki Kawashima ◽

Susumu Kanzaki ◽

Fan Yang ◽

Tomoe Kinoshita ◽

Keiichi Hanaki ◽

...

Keyword(s):

Short Stature ◽

Growth Retardation ◽

Cleavage Site ◽

Intrauterine Growth Retardation ◽

Growth Factor Receptor ◽

Heterozygous Mutation ◽

Β Subunit ◽

Direct Dna Sequencing ◽

Intrauterine Growth ◽

Igf I

Context: Mouse knockout models have clearly demonstrated the critical importance of IGF-I and IGF receptor type 1 (IGF-IR) for embryonic growth as well as postnatal growth. Objective: We hypothesized that mutations of IGF-IR gene might predispose to short stature in children born with intrauterine growth retardation (IUGR). Patients: Twenty-four children with unexplained IUGR (birth weight < −1.5 sd) and short stature (<−2.0 sd) were screened for abnormalities of the IGF-IR gene. Methods: Direct DNA sequencing was used to identify IGF-IR gene mutations. Unprocessed IGF-IR proreceptor in fibroblasts was detected by immunoblot analysis. Functions of mutated IGF-IR in fibroblasts were evaluated by IGF-I binding, and IGF-I-stimulated DNA synthesis and β-subunit autophosphorylation. Results: We found the following results: 1) a heterozygous mutation (R709Q) changing the cleavage site from Arg-Lys-Arg-Arg to Arg-Lys-Gln-Arg was identified in a 6-yr-old Japanese girl (case 1) and her mother who also had IUGR with short stature (case 2); 2) fibroblasts from case 2 contained more IGF-IR proreceptor protein (189 ± 26% of normal) and less mature β-subunit protein (63 ± 12%); 3) [125I]IGF-I binding to fibroblasts from case 2 was reduced, compared with normal control (0.61 ± 0.16 × 106vs. 1.14 ± 0.12 × 106 sites per cell; P < 0.05); and 4) both IGF-I-stimulated [3H]thymidine incorporation and IGF-IR β-subunit autophosphorylation were low in fibroblasts from case 2, compared with those of control (P < 0.05). Conclusions: These findings strongly suggest that this mutation leads to failure of processing of the IGF-IR proreceptor to mature IGF-IR and causes short stature and IUGR.

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