Noonan‐like syndrome with loose anagen hair associated with growth hormone insensitivity and atypical neurological manifestations

Capalbo, Donatella; Melis, Daniela; Martino, Lucia De; Palamaro, Loredana; Riccomagno, Stefania; Bona, Gianni; Cordeddu, Viviana; Pignata, Claudio; Salerno, M.

doi:10.1002/ajmg.a.35234

Cited by 17 publications

(17 citation statements)

References 21 publications

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“…NS/LAH patients were frequently affected by proven GHD [Mazzanti et al, 2003;Cordeddu et al, 2009] and only one patient with referred condition of GH insensitivity (GHI) has been reported [Capalbo et al, 2012a]. In this study, we documented that children with NS/LAH (Mazzanti Syndrome) were all short, approximately À3 SDS in height below the general Italian population standards, in line with previous data [Malaquias et al, 2012], and their TH.…”

Section: Discussionsupporting

confidence: 88%

GH Therapy and first final height data in Noonan‐like syndrome with loose anagen hair (Mazzanti syndrome)

Mazzanti

Tamburrino

Scarano

et al. 2013

American J of Med Genetics Pt A

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Noonan-like syndrome with loose anagen hair (NS/LAH or Mazzanti Syndrome) is caused by a single missense mutation in SHOC2 promoting tN-myristoylation of the encoded protein.Cardinal features include facial features resembling NS, short stature often associated with proven growth hormone deficiency (GHD), typical ectodermal anomalies, and distinctive behavior. Overall, the clinical features are more severe than those generally observed in NS, even though the phenotype improves with age. We report on growth and pubertal trend in seven patients heterozygous for a mutated SHOC2 allele, treated with longterm GH-therapy, and final height (FH) in three of them. They were approximately À3 SDS below the Italian general population standards, they had very low IGF1 levels at baseline and GHD at pharmacological tests. All patients were treated with GH (0.035 mg/kg/day) for a mean period of 8.49 AE 5.72 years. After the 1st year of GH-therapy, IGF1 level and height velocity had increased. Three of 7 patients reached the FH (À2.34 AE 0.12 SDS) at 18.25 AE 0.73 years, after GH administration for 12.39 AE 2.12 years. Pubertal development was variable, showing a prolonged and delayed puberty or rapid pubertal progression that could impair the FH. Overall, our data in this small cohort suggest that NS/LAH patients benefit from long-term GH-therapy, although they do not show the characteristic catch-up growth of isolated GHD. While the observed growth and pubertal behavior is consistent with a dysfunction of the hypothalamic-pituitarygonadal axis, the functional link between SHOC2 and the GH/ IGF signaling pathways remains to be clarified.

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Section: Discussionsupporting

confidence: 88%

GH Therapy and first final height data in Noonan‐like syndrome with loose anagen hair (Mazzanti syndrome)

Mazzanti

Tamburrino

Scarano

et al. 2013

American J of Med Genetics Pt A

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“…The observation that untreated precocious puberty is generally associated with impaired adult height due to bone age advancement and that short stature is per se a hallmark of TS prompted us to undertake a treatment with GnRH analog [26]. Again, despite a normal GH secretion following a pharmacological stimulation test [27], evidence indicates that a GH treatment may improve adult height in TS as well as in other syndromes [28,29]. For this reason, the initiation of GH therapy is currently considered as soon as growth failure is evidenced even though short stature is not present [4].…”

Section: Discussionmentioning

confidence: 99%

Precocious puberty in Turner Syndrome: report of a case and review of the literature

et al. 2012

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Introduction: Turner Syndrome (TS) is caused by monosomy or structural abnormalities of the X chromosome, with a prevalence of about 1/2000 females live birth. Most important clinical features of TS are short stature and gonadal failure. Approximately one third of girls with TS may undergo spontaneous puberty. Here we report on the case of a girl with a rare 45X0/47XXX mosaic TS exhibiting a precocious puberty. Case report: The patient was diagnosed with TS at the age of 4 years, upon a diagnostic work-up for dysmorphic features. Chromosome analysis revealed a mosaic karyotype (45X0/47XXX). She presented with normal height and normal growth velocity so that Growth Hormone (GH) therapy was not started. She was referred to our Department at the age of 7 years and 10 months, because of vaginal bleeding. A physical examination revealed a Tanner stage III for breast and Tanner stage III for pubic hair development. Height and weight were within the normal range for age. Psychological evaluation showed moderate global developmental delay, together with emotional and social immaturity and reading difficulties. The growth rate was accelerated. Her bone age was 10 years. Pelvic ultrasound demonstrated increased size for age of both the uterus and the ovaries, with bilateral ovarian follicles. GnRH stimulation test revealed pubertal response of gonadotropins (peak LH 22.5 mIU/ml). MRI of the brain was normal. These clinical, radiologic and laboratory findings were consistent with a diagnosis of idiopathic central precocious puberty; therefore, GnRH analog therapy was started, in order to slow pubertal progression and to preserve adult stature. Furthermore, GH treatment was added to further improve adult height. Conclusion: Our case highlights the possibility of precocious puberty as an atypical clinical feature of TS. Thus, precocious puberty may occur in TS girls when a dosage compensation by the cell line with more than two X chromosomes allows normal ovarian function. GnRH analog therapy in addition to GH treatment should be recommended in TS girls with precocious puberty in order to slow pubertal progression and to preserve adult stature.

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“…Mild to moderate GH deficiency (GHD) and insensitivity to growth hormone (GHI) have been suggested as causes of short stature in NS/LAH patients [Cordeddu et al, 2009;Mazzanti et al, 2013]. To date, only two studies have examined the effects of GH treatment on NS/LAH [Capalbo et al, 2012a;Mazzanti et al, 2013]. In those reports, the effectiveness of GH therapy was limited because of partial GHI.…”

Section: Introductionmentioning

confidence: 99%

Improved growth velocity of a patient with Noonan‐like syndrome with loose anagen hair (NS/LAH) without growth hormone deficiency by low‐dose growth hormone therapy

Takasawa

Takishima

Morioka

et al. 2015

American J of Med Genetics Pt A

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Noonan-like syndrome with loose anagen hair (NS/LAH; OMIM 607721) is caused by a heterozygous c.4A>G mutation in SHOC2. Most cases exhibit both growth hormone deficiency (GHD) and growth hormone insensitivity (GHI) and thus require a high dose of growth hormone (GH) therapy (e.g., 35-40 µg/kg/day). We report on a genetically diagnosed NS/LAH patient manifesting severe short stature (-3.85 SDs) with low serum level of IGF1, 30 ng/ml. The peak levels of GH stimulation tests were within the normal range, and GHI was not observed in the IGF1 generation test. However, with low-dose GH therapy (25 µg/kg/day) for two years, IGF1 level and height were remarkably improved (IGF1: 117 ng/ml, height SDs: -2.20 SDs). Further, catch-up of motor development and improvement of the proportion of extending limbs to trunk were observed (the Developmental Quotient score increased from 68 to 98 points, and the relative sitting height ratio decreased from 0.62 to 0.57). Our results suggest that endocrinological causes for short stature are variable in NS/LAH and that GH therapy should be considered as a possible treatment for delayed development in NS/LAH.

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Noonan‐like syndrome with loose anagen hair associated with growth hormone insensitivity and atypical neurological manifestations

Cited by 17 publications

References 21 publications

GH Therapy and first final height data in Noonan‐like syndrome with loose anagen hair (Mazzanti syndrome)

GH Therapy and first final height data in Noonan‐like syndrome with loose anagen hair (Mazzanti syndrome)

Precocious puberty in Turner Syndrome: report of a case and review of the literature

Improved growth velocity of a patient with Noonan‐like syndrome with loose anagen hair (NS/LAH) without growth hormone deficiency by low‐dose growth hormone therapy

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