Abstract
Holoprosencephaly (HPE) is the most common developmental defect of the forebrain and midface in humans. sporadic and inherited mutations in the human sonic hedgehog (SHH) gene cause 37% of familial HPE. A couple was referred to our unit with a family history of two spontaneous first trimester miscarriages and a daughter with HPE who presented early neonatal death. The father had a repaired median cleft lip, absence of central incisors, facial medial hypoplasia, and cleft palate. Intelligence and a brain CT scan were normal. Direct paternal sequencing analysis showed a novel nonsense mutation (W127X). Facial characteristics are considered as HPE microforms, and the pedigree suggested autosomal dominant inheritance with a variable expression of the phenotype. This study reinforces the importance of an exhaustive evaluation of couples with a history of miscarriages and neonatal deaths with structural defects.
Highlights
(HPE) is the most common developmental defect of the forebrain and midface in humans [1], and it is a frequent cause of prenatal death, with an estimated frequency of 1/250 abortions and 1/16,000 live births [2]
A couple was referred to our unit with a family history of two spontaneous first trimester miscarriages and a daughter with HPE who presented early neonatal death
A couple was referred to the Genetics Reproductive Clinic with a family history of two spontaneous first trimester miscarriages and a daughter with holoprosencephaly and cebocephaly who presented early neonatal death
Summary
(HPE) is the most common developmental defect of the forebrain and midface in humans [1], and it is a frequent cause of prenatal death, with an estimated frequency of 1/250 abortions and 1/16,000 live births [2]. Sporadic and inherited mutations in the human Sonic Hedgehog (SHH) gene have been shown to cause holoprosencephaly (HPE3 (MIM 236100)) in 3.7% of sporadic, 18% of familial cases and 37% families with autosomal dominant transmission [7]. Mutations and microdeletions in other genes (SIX3, ZIC2, and TG1F), and environmental factors such as maternal diabetes, alcohol, and retinoic acid exposure during pregnancy as well as some monogenic syndromes can cause HPE [8, 9]. We describe a novel SHH mutation in the male partner of a couple with pregnancy loss and a daughter with a severe expression in the phenotype
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
