Pathologic macrocephaly may be caused by congenital anatomic abnormalities, genetic conditions, or by environmental events.Many genetic conditions are associated with macrocephaly, including familial macrocephaly related to the holgate gene, autism, PTEN mutations such as Cowden disease, neurofibromatosis type 1, and tuberous sclerosis; overgrowth syndromes such as Sotos syndrome (cerebral gigantism), Weaver syndrome, Simpson–Golabi–Behmel syndrome (bulldog syndrome), and macrocephaly-capillary malformation (M-CMTC) syndrome; neurocardiofacial-cutaneous syndromes such as Noonan syndrome, Costello syndrome, Gorlin syndrome, (also known as Basal Cell Nevus Syndrome) and cardiofaciocutaneous syndrome; Fragile X syndrome; leukodystrophies (brain white matter degeneration) such as Alexander disease, Canavan disease, and megalencephalic leukoencephalopathy with subcortical cysts; and glutaric aciduria type 1 and D-2-hydroxyglutaric aciduria.At one end of the genetic spectrum, duplications of chromosomes have been found to be related to autism and macrocephaly; at the other end, deletions of chromosomes have been found to be related to schizophrenia and microcephaly.Environmental events associated with macrocephaly include infection, neonatal intraventricular hemorrhage (bleeding within the infant brain), subdural hematoma (bleeding beneath the outer lining of the brain), subdural effusion (collection of fluid beneath the outer lining of the brain), and arachnoid cysts (cysts on the brain surface).In research, cranial height or brain imaging may be used to determine intracranial volume more accurately.
The previously listed genetic mechanisms result in twice the normal amount of these two genes and cause chromosome 6q24 TNDM. ZFP57 Gene
Third, mothers hypomethylation defects (a genetic defect that stops the allele from getting  a methyl group, which would inhibit transcription) can occur from an isolated genomic imprinting or occur as a defect called, "hypomethylation imprinted loci" (HIL). HIL is defined as the loss of a methyl group in the 5-methylcytosine nucleotide at a fixed position on a chromosome. Homozygous ( having two of the same alleles) or heterozygous (defined as having one each of two different alleles) ZFP57 pathogenic variant make up almost half of TNDM-HIL, but the other causes of HIL are unknown.Moreover, half of TNDM patients that contain chromosome 6q24-related TNDM experiencing re-occurrence of diabetes during their childhood or young adulthood. The onset of insulin resistance and increased insulin requirements are associated with puberty and pregnancy initiating the relapse of diabetes. In the event of remission, individuals do not show symptoms or impairment Beta-cell function in the fasting state. Insulin secretory response to intravenous glucose loading might be abnormal in those destined to have a relapse of diabetes. TNDM caused by 6q24 genomic defects are always associated with IGUR. Other contributing factors are umbilical hernia and enlarged tongue, which are present in 9 and 30% of patients with chromosome 6q24 related TNDM. Diagnosis
Diagnosis of neonatal diabetes is complicated by the fact that hyperglycemia is common in neonates – particularly in preterm infants, 25–75% of whom have hyperglycemia.