The Btk enzyme plays an essential role in the maturation of B cells in the bone marrow, and when mutated, immature pro-B lymphocytes are unable to develop into pre-B lymphocytes, which normally develop into mature (naive) B cells that leave the bone marrow into the blood stream.The disorder is inherited in an X-linked recessive fashion (as the gene linked to it is on the X chromosome) and is almost entirely limited to the sons of asymptomatic female carriers. This is because males have only one copy of the X chromosome, while females have two copies; one normal copy of an X chromosome can compensate for mutations in the other X chromosome, so they are less likely to be symptomatic.There is 30–50% chance of XLA patients having a positive family history of genetic inheritance. The rest of the cases occur as random mutations. If a carrier female gives birth to a male child, there is a 50% chance that the male will have XLA. A carrier female has a 25% chance overall of giving birth to an affected male child. An XLA patient will pass on the gene, and all of his daughters will be XLA carriers, meaning that any male grandchildren from an XLA patients daughters have a 50% chance of inheriting XLA. A female XLA patient can arise only as the child of an XLA patient and a carrier mother. XLA can also rarely result from a spontaneous mutation in the fetus of a non-carrier mother.
There are three points that need to be met for a diagnosis of DLD:
The child has language difficulties that create obstacles to communication or learning in everyday life,
The childs language problems are unlikely to resolve by five years of age, and
The problems are not associated with a known biomedical condition such as brain injury, neurodegenerative conditions, genetic conditions or chromosome disorders such as Down syndrome, sensorineural hearing loss, autism spectrum disorder, or intellectual disability.For research and epidemiological purposes, specific cutoffs on language assessments have been used to document the first criterion. Tomblin et al. proposed the EpiSLI criterion, based on five composite scores representing performance in three domains of language (vocabulary, grammar, and narration) and two modalities (comprehension and production). Children scoring in the lowest 10% on two or more composite scores are identified as having language disorder. The second criterion, persistence of language problems, can be difficult to judge in a young child, but longitudinal studies have shown that difficulties are less likely to resolve for children who have poor language comprehension, rather than difficulties confined to expressive language. In addition, children with isolated difficulties in just one of the areas noted under subtypes tend to make better progress than those whose language is impaired in several areas.The third criterion specifies that DLD is used for children whose language disorder is not part of another biomedical condition, such as a genetic syndrome, a sensorineural hearing loss, neurological disease, autism spectrum disorder or intellectual disability – these were termed differentiating conditions by the CATALISE panel.