Developmental Delay
22q11.2 deletion syndrome - Patients commonly have speech delay although they ultimately acquire normal language skills. The mean IQ is 70 (ranging from completely normal to moderately disabled). Approximately 25% of patients develop ADHD. Bipolar disorder, autistic spectrum disorder, or schizophrenia/schizoaffective disorder may be present in 10-30% of older patients.
CHARGE syndrome - Patients typically have mental retardation and developmental delay. Poor vision and hearing (resulting in decreased visual and auditory input) can also contribute to the developmental delay.
LAD Type II - Patients have severe mental retardation, microcephaly, and hypotonia. Cortical atrophy has been described. Patients also have short stature and have distinct facial features with a depressed nasal bridge. Skin and lung infections are milder than in LAD I.
Adenosine Deaminase Deficiency
Adenosine Deaminase Deficiency patients may develop neurologic symptoms including developmental delay, hypotonia, head lag, and seizures. These symptoms may improve following treatment with PEG-ADA therapy.
The majority (2/3) of PNP deficiency patients develop early onset neurological abnormalities: these can include mental retardation, ataxia, spasticity, tremor, and hyperactivity.
Mevalonic aciduria patients are chacterized by recurrent febrile episodes similar to hyper IgD syndrome. However, patients also exhibit dysmorphic facial features (microcephaly, low-set posteriorly rotated ears, down slanted palpebral fissures), ataxia, mental retardation, cataracts, and failure to thrive.
Patients with the severe infant onset form of Dyskeratosis Congenita (Hoyeraal-Hreidarsson syndrome) can have developmental delay.
Kabuki syndrome patients typically have mental retardation (IQ <70). Delays in speech and language acquisition have been reported.
CINCA (NOMID) patients are characterized by recurrent fevers with urticaria, arthritis, and severe neurological symptoms (mental retardation, seizures, cerebral atrophy, and sensorineural hearing loss)
Chediak-Higashi syndrome - Patients develop neurologic abnormalities including developmental delay, peripheral neuropathy (causing weakness and sensory deficits), cerebellar ataxia, seizures, and cranial nerve palsies.
Griscelli syndrome type 2 patients may have neurologic abnormalities such as developmental delay, ataxia, seizures, dysarthria, and hemiplegia. This disease is also characterized by mild neutropenia, impaired CD8 and NK cell cytotoxicity, oculocutaneous hypopigmentation, and a predisposition to develop hemophagocytic lymphohistiocytosis.
Biotinidase Deficiency
Biotinidase deficiency results in impaired humoral and cell-mediated immunity. Mucocutaneous candidiasis and systemic bacterial/viral infections occur. Neurologic features include seizures, developmental delay, ataxia, and hypotonia. Dermatitis and alopecia also occur. These symptoms improve with dietary biotin supplementation.
ICF Syndrome (Immunodeficiency, centromeric instability, facial anomalies) patients typically have developmental delay and mental retardation.