Molecular Characteristics for Families

The homozygous variants (both the pairs of DNA inherited from either parent carry the genetic alteration) in HHAT underlie an autosomal recessive clinical entity (multiple malformation syndrome) characterized by small head , small cerebellar vermis (small of the terminal region of the brain), holoprosencephaly (improper separation of the midline of the brain during development), abnormal eye and face, skeletal dysplasia (defects of the bone and cartilage) and sex reversal (normal external and internal genitals but abnormal karyotype).
HHAT (Hedgehog acyl-transferase) gene is involved in making a protein which ensures proper functioning of the developmentally important signaling pathway in the human body called the hedgehog signaling pathway. The important genes within this pathway ensures proper development of symmetry of the body, development of limbs, nervous system, eyes, bones, cartilage, muscles and the genitourinary system. As there is defect in functioning of HHAT gene due to alterations in its normal DNA sequence, it further disrupts the functioning of the downstream proteins in the hedgehog signaling pathway. This might be the reason for the diverse clinical features seen in the affected individuals with HHAT-related multiple congenital anomaly syndrome.