Oto-palato-digital syndrome is the generalised term for two conditions, oto-palato-digital syndrome type I (OPD1) and oto-palato-digital syndrome type II (OPD2), that are both

X-linked recessive X-linked recessive inheritance is a mode of inheritance in which a mutation in a gene on the X chromosome causes the phenotype to be always expressed in males (who are necessarily homozygous for the gene mutation because they have one X and one Y ...

genetic disorders with overlapping

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological pr ...

s. The most severe phenotypes of each syndrome occur only in males, with females generally having attenuated forms of the condition, although this does not apply to all individual cases. Some writers conceptualise oto-palato-digital syndrome as a

spectrum disorder A spectrum disorder is a mental disorder that includes a range of linked conditions, sometimes also extending to include singular symptoms and traits. The different elements of a spectrum either have a similar appearance or are thought to be cause ...

including two similarly-presenting genetic syndromes, frontometaphyseal dysplasia and Melnick-Needles syndrome. The conditions are characterised by skeletal abnormalities,

cleft palate A cleft lip contains an opening in the upper lip that may extend into the nose. The opening may be on one side, both sides, or in the middle. A cleft palate occurs when the palate (the roof of the mouth) contains an opening into the nose. The ...

(a hole in the roof of the mouth), and hearing loss. These symptoms are common to craniofacial syndromes as a whole. Hand defects are particularly associated. Of the conditions, OPD1 has the milder phenotype, with normal intelligence and modestly reduced stature. In OPD2, the characteristic facial features are more severe and

intellectual disability Intellectual disability (ID), also known as general learning disability in the United Kingdom and formerly mental retardation, Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010). is a generalized neurodevelopmental disorder characterized by signif ...

frequent; most OPD2 cases in males are stillborn or die during infancy. As an X-linked recessive disorder, both forms are generally more severe in males, who have one

X chromosome The X chromosome is one of the two sex-determining chromosomes (allosomes) in many organisms, including mammals (the other is the Y chromosome), and is found in both males and females. It is a part of the XY sex-determination system and XO sex ...

, than females, who have two. Reports from patients of their experiences demonstrate a broad spectrum of symptom severity, including within families, which has also been reported in the medical literature. Oto-palato-digital syndrome is caused by a

gain-of-function mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...

in the ''

FLNA Filamin A, alpha (FLNA) is a protein that in humans is encoded by the ''FLNA'' gene. Function Actin-binding protein, or filamin, is a 280-kD protein that crosslinks actin filaments into orthogonal networks in cortical cytoplasm and participate ...

'' gene on the X chromosome. Women with one copy of the mutation will with each pregnancy have a 50% chance of passing it down to each child. Men with one copy of the mutation will pass it down to all daughters, and will not pass the mutation down to sons.

Germline mosaicism Germline mosaicism, also called gonadal mosaicism, is a type of genetic mosaicism where more than one set of genetic information is found specifically within the gamete cells; conversely, somatic mosaicism is a type of genetic mosaicism found in So ...

for OPD1 has been reported, meaning that unaffected parents with an affected child have a slightly increased risk of bearing another. The prevalence of oto-palato-digital syndrome is unknown, but estimated to be below 1 in 100,000.

References

{{Congenital malformations and deformations of musculoskeletal system Genetic diseases and disorders X-linked recessive disorders Hearing loss with craniofacial syndromes