ESPE Abstracts

Introduction: Noonan syndrome-like disorder with loose anagen hair (NSLH1), also known as Mazzanti syndrome (OMIM#607721) is a RASopathy due to missense mutation (c.4A>G, p.Ser2Gly) in SHOCK2 gene. The NSHL1 is characterized by Noonan syndrome-like facial dysmorphisms, easily pluckable, slow growing, sparse and thin hair, growth retardation, variable neurocognitive impairment and cardiac anomalies.

Aim: To present an additional new phenotypic variation associated with the c.4A>C change in NSHL1.

Material and methods: A 2 ^3/12 years old Greek girl was diagnosed with NSHL1. She presented failure to thrive since 34^th day of life and referred to the Pediatric Endocrinology Unit at the age of 9 months. She was born at 38+2 days weeks, small for gestational age in weight and length, with no episodes of hypoglycemia. Fetal ultrasound at 12^th week of gestation revealed increased cervical transparency. Chorionic villi sample analysis revealed a normal karyotype (46, XX). The patient was diagnosed with atrial septal defect (ASD) and pulmonary valve stenosis at the age of 5 months and was under investigation for gastro-oesophageal reflux.

Results: At presentation her weight and height were 5,550 gr (<3^rd centile) and 63,5 cm (<3^rd centile), respectively. Head circumference was 44,5 cm,50^th centile, despite the evident prominent fronthead. Clinical examination revealed low set ears, flat nasal bridge, epicanthal folds, long philtrum, bell-shaped thorax, remarkably red, sparse, thin, easy pluckable hairs. Neurological evaluation revealed mild hypotonia and congenital torticollis, while developmental milestones have been achieved within the normal range. Due to the audible systolic murmur and the history of ASD, a new ultrasound of the heart confirmed the wide ASD accompanied by dilatation of both right atrium and ventricle. Coeliac disease and metabolic disorders were excluded. The ophthalmological and audiometric evaluation were within normal. The diagnosis of growth hormone deficiency was established. Hypothalamic-pituitary MRI imaging revealed normal findings. Next Generation Sequencing analysis was performed, which allowed the heterozygous dominant missense change (c.4A>C, p. Ser2Gly) to be identified in SHOC2.

Conclusion: NSLH1 is characterized by distinctive features resembling Noonan syndrome. The most prevalent feature is the easily pluckable, thin, sparse and slow growing hair. In this case the patient presents most characteristics of the typical NSLH1 phenotype, with the addition of the oddly red hair. This trait is present in contrast with the ‘silver-blonde hair’, described in the initial presentation of the disorder by Mazzanti. It is crucial to provide evidence for phenotypic variations in increased clinical suspicion.