ESPE Abstracts

Introduction: The Sonic Hedgehog (SHH) gene is involved in the development of midline structures. Pathogenic variantd in this gene have been associated to holoprosencenphaly 3; Microphthalmia with coloboma 5; Schizencephaly; and Single median maxillary central incisor syndrome (SMMCIS). All of them are inherited in an autosomal dominant pattern and exhibit incomplete penetrance as well as variable expressivity.

Case Report: A 6-year-old girl in follow-up in our clinics for postnatal short stature and congenital microcephaly. Neonatal anthropometry was normal (weight -1.81 SD, length -1.5 SD) except for the presence of microcephaly (HC -2.56 SD). At birth, she required admission to neonatology due to generalized cyanosis coinciding with infancy, a CT scan of the paranasal sinuses was performed and anterior mucosal thickening of the nostrils was diagnosed. In addition, he has required follow-up in Nephrology due to unilateral pyeloureteral stenosis, in Cardiology due to interventricular communication and in Neurology due to ADHD. Physical examination revealed a weight -2.26 SD, height -2.17 SD, WC -5.89 SD, sitting height -0.77 SD and normal fathom, as well as a single upper central incisor (Image 1) and a deviation of the nasal septum without other dysmorphic features. On the other hand, the mother presents a similar phenotype without single central incisor but a height of -3.13 SD. It was requested a karyotype and cerebral MRI, without anormal findings. We performed a skeletal dysplasias panel using Next Generation Sequencing (NGS). A pathogenic variant in the SHH gene (NM_000193.3:c.449C>T; p.(Thr150Met)) was found. It is not previously described in the literature. Segregation study has been requested from the parents and sister.

Discussion: Phenotypic spectrum of SHH gene include the presence of holoprosencephaly, microcephaly (33%), facial dysmorphisms (midfacial hypoplasia, hypotelorism, flat nasal root, cleft lip/palate and a single upper central incisor), congenital obstruction of the nasal airway (90%), hypopituitarism (15%), short stature and intellectual disability (50%). It also has being associated cardiac or genitourinary malformations with less frequency.

Conclusions: The non-pathological brain imaging and the presence of single upper central incisor, short stature, microcephaly, alterations of the nasal airway, cardiac malformations and genitourinary malformations makes SMMCI the most plausible diagnosis.