Muscle spasms as presenting feature of Nivelon-Nivelon-Mabile syndrome

Hedgehog acyltransferase gene (HHAT)-associated Nivelon-Nivelon-Mabile syndrome (NNMS) is a rare genetic disorder of multiple system involvement with microcephaly, central nervous system malformations, skeletal dysplasia, and 46,XY sex reversal. Other variable and inconsistent features reported in this disorder are muscle spasms, facial dysmorphism, prenatal onset growth restriction, microphthalmia, and holoprosencephaly. This is the sixth postnatal reported patient with biallelic variants in HHAT gene, who presented with microcephaly, short stature, muscle hypertrophy, muscle spasms, and facial dysmorphism. The most prominent and presenting finding in this patient were muscle hypertrophy and muscle spasms which had a clinical response to phenytoin and acetazolamide treatment. Our report emphasizes the phenotypic variability of NNMS and further reiterates muscle spasms as an important clinical manifestation of this extremely rare condition.

Automated summary

Nivelon-Nivelon-Mabile syndrome (NNMS) is a rare genetic disorder characterized by multiple system involvement, including microcephaly, central nervous system malformations, skeletal dysplasia, and 46,XY sex reversal. Other variable features reported in this disorder are muscle spasms, facial dysmorphism, prenatal growth restriction, microphthalmia, and holoprosencephaly. This study reports a postnatal patient with biallelic variants in the Hedgehog acyltransferase gene (HHAT) presenting with microcephaly, short stature, muscle hypertrophy, muscle spasms, and facial dysmorphism. Muscle hypertrophy and muscle spasms in this patient showed clinical response to phenytoin and acetazolamide treatment, highlighting the importance of muscle spasms as a clinical manifestation in this extremely rare condition.