BACKGROUND Noonan syndrome (NS) is an autosomal dominant disorder characterised by genotypic and phenotypic variability. The prevalence and global frequency of NS at live birth almost all over the world has been reported as one in 1000–2500 individuals. Various symptoms have been reported for this abnormality such as short stature, unusual facial characteristics, congenital heart abnormalities, developmental complications, and an elevated tumour incidence rate. Short stature is its most striking manifestation. At birth, they are usually a normal length and weight, but growth slows over time. More than 90 mutations causing Noonan syndrome have been identified in the PTPN11 gene, which is involved in protein tyrosine phosphatase SHP-2 expression, on chromosome 12 (12q24), account for up to 50% of NS patients. CASE REPORT A 5,6 year old girl was admitted to our institute because of short stature. Paternal family history was positive for short stature. Prenatal chromosomal analysis showed that the fetus had a karyotype of 46 XX; t (10;12)(q24,3; q24,31). The same translocation was found in her father. Many genes are involved in these two chromosomal locations, such as PTPN11 gene. Examination at the admission revealed non dismorfic phenotype, and bot her height and weight were below the 3rd percentile compared to the normal peers. Bone age was delayed respect her chronological age (3 years vs 5,6 years). Laboratory tests revealed TSHlevels increased(8,73 µUI/ml; normal range 0,30–4,50 µUI/ml), fT4 levels within the normal range and ACTH levels decreased (4,8 pg/ml; normal ranges 7–51 pg/ml).Using GH stimulation testing with Arginine and Glucagon,GH deficiency was confirmed: peak GH levels were 2,08 ng/ml and 5,6 ng/ml, respectively. Therefore, recombinant human GH was introduced(0,8 mg/day for six days in a week). ConclutionS A diagnosis of NS should be kept in mind in all patients with short stature. The genetic aetiology may not be clinically apparent because the underlying monogenic cause is quite rare and lacks distinctive features, or the patient may represent a milder phenotypic spectrum of the disorder, without all of the characteristic features. A genetic approach to the diagnosis of short stature is necessary in selected patients who are more likely to have a genetic contributor to their short stature.
A case of short stature: a milder phenotypic spectrum of noonan syndrome?
PETTOELLO MANTOVANI, MASSIMO
2017-01-01
Abstract
BACKGROUND Noonan syndrome (NS) is an autosomal dominant disorder characterised by genotypic and phenotypic variability. The prevalence and global frequency of NS at live birth almost all over the world has been reported as one in 1000–2500 individuals. Various symptoms have been reported for this abnormality such as short stature, unusual facial characteristics, congenital heart abnormalities, developmental complications, and an elevated tumour incidence rate. Short stature is its most striking manifestation. At birth, they are usually a normal length and weight, but growth slows over time. More than 90 mutations causing Noonan syndrome have been identified in the PTPN11 gene, which is involved in protein tyrosine phosphatase SHP-2 expression, on chromosome 12 (12q24), account for up to 50% of NS patients. CASE REPORT A 5,6 year old girl was admitted to our institute because of short stature. Paternal family history was positive for short stature. Prenatal chromosomal analysis showed that the fetus had a karyotype of 46 XX; t (10;12)(q24,3; q24,31). The same translocation was found in her father. Many genes are involved in these two chromosomal locations, such as PTPN11 gene. Examination at the admission revealed non dismorfic phenotype, and bot her height and weight were below the 3rd percentile compared to the normal peers. Bone age was delayed respect her chronological age (3 years vs 5,6 years). Laboratory tests revealed TSHlevels increased(8,73 µUI/ml; normal range 0,30–4,50 µUI/ml), fT4 levels within the normal range and ACTH levels decreased (4,8 pg/ml; normal ranges 7–51 pg/ml).Using GH stimulation testing with Arginine and Glucagon,GH deficiency was confirmed: peak GH levels were 2,08 ng/ml and 5,6 ng/ml, respectively. Therefore, recombinant human GH was introduced(0,8 mg/day for six days in a week). ConclutionS A diagnosis of NS should be kept in mind in all patients with short stature. The genetic aetiology may not be clinically apparent because the underlying monogenic cause is quite rare and lacks distinctive features, or the patient may represent a milder phenotypic spectrum of the disorder, without all of the characteristic features. A genetic approach to the diagnosis of short stature is necessary in selected patients who are more likely to have a genetic contributor to their short stature.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
