Brain MRI shows vermis atrophy or hypoplasic. Cerebral and cerebellar atrophy with white matter changes in some cases.

The diagnosis of IP is established by clinical findings and occasionally by corroborative skin biopsy. Molecular genetic testing of the NEMO IKBKG gene (chromosomal locus Xq28) reveals disease-causing mutations in about 80% of probands. Such testing is available clinically.

In addition, females with IP have skewed X-chromosome inactivation; testing for this can be used to support the diagnosis.

Many people in the past were misdiagnosed with a second type of IP, formerly known as IP1. This has now been given its own name - 'Hypomelanosis of Ito' (incontinentia pigmenti achromians). This has a slightly different presentation: swirls or streaks of hypopigmentation and depigmentation. It is "not" inherited and does not involve skin stages 1 or 2. Some 33–50% of patients have multisystem involvement — eye, skeletal, and neurological abnormalities. Its chromosomal locus is at Xp11, rather than Xq28.

13q deletion syndrome can only be definitively diagnosed by genetic analysis, which can be done prenatally or after birth. Increased nuchal translucency in a first-trimester ultrasound may indicate the presence of 13q deletion.

Diagnosis of MSS is based on clinical symptoms, magnetic resonance imaging (MRI) of the brain (cerebellar atrophy particularly involving the cerebellar vermis), and muscle biopsy.

It can be associated with mutations of the SIL1 gene, and a mutation can be found in about 50% of cases.

Differential diagnosis includes Congenital Cataracts Facial Dysmorphism Neuropathy (CCFDN), Marinesco–Sjögren like syndrome with chylomicronemia, carbohydrate deficient glycoprotein syndromes, Lowe syndrome, and mitochondrial disease.

Neuroimaging like MRI is important. However, there was considerable intrafamilial variability regarding neuroimaging, with some individuals showing normal MRI findings. Early individual prognosis of such autosomal recessive cerebellar ataxias is not possible from early developmental milestones, neurological signs, or neuroimaging.

Microlissencephaly can be diagnosed by prenatal MRI. MRI is better than ultrasound when it comes to detecting microlissencephaly or MSGP prenatally.

The ideal time for proper prenatal diagnosis is between the 34th and 35th gestational week which is the time when the secondary gyration normally terminates. In microlissencephaly cases, the primary sulci would be unusually wide and flat while secondary sulci would be missing.

At birth, lissencephaly with a head circumference of less than minus three standard deviations (< –3 SD) is considered microlissencephaly.

Although genetic diagnosis in patients with MLIS is challenging, exome sequencing has been suggested to be a powerful diagnostic tool.

Treatment for MSS is symptomatic and supportive including physical and occupational therapy, speech therapy, and special education. Cataracts must be removed when vision is impaired, generally in the first decade of life. Hormone replacement therapy is needed if hypogonadism is present.

Three dimensional (3D) T1W, Axial, coronal, sagittal imaging is excellent for differentiation between gray matter and white matter acquisition of high-resolution anatomic information.T2W, Axial and coronal imaging for acquisition of high-resolution anatomic information; delineation of cortex, white matter, and gray matter nuclei. Diffusion tensor, axial imaging is used for evaluation of white matter microstructural integrity, identification of white matter tracts. CISS, axial + MPR imaging for evaluation of cerebellar folia, cranial nerves, ventricles, and foramina. Susceptibility weighted axial scan for Identification and characterization of hemorrhage, blood products, calcification, and iron accumulation.

Prognoses for 3C syndrome vary widely based on the specific constellation of symptoms seen in an individual. Typically, the gravity of the prognosis correlates with the severity of the cardiac abnormalities. For children with less severe cardiac abnormalities, the developmental prognosis depends on the cerebellar abnormalities that are present. Severe cerebellar hypoplasia is associated with growth and speech delays, as well as hypotonia and general growth deficiencies.

Microlissencephaly is considered a more severe form than microcephaly with simplified gyral pattern. Microlissencephaly is characterized by a smooth cortical surface (absent sulci and gyri) with a thickened cortex (> 3 mm) and is usually associated with other congenital anomalies. Microcephaly with a simplified gyral pattern has too few sulci and normal cortical thickness (3 mm) and is usually an isolated anomaly.

Three main points in diagnosing thumb hypoplasia are: width of the first web space, instability of the involved joints and function of the thumb. Thorough physical examination together with anatomic verification at operation reveals all the anomalies. An X-ray of the hand and thumb in two directions is always mandatory. When the pediatrician thinks the condition is associated with some kind of syndrome other tests will be done. More subtle manifestations of types I and II may not be recognized, especially when more obvious manifestations of longitudinal radial deficiency in the opposite extremity are present. Therefore, a careful examination of both hands is important.

Prenatal Diagnosis:

- Aymé, "et al." (1989) reported prenatal diagnosis of Fryns syndrome by sonography between 24 and 27 weeks.

- Manouvrier-Hanu et al. (1996) described the prenatal diagnosis of Fryns syndrome by ultrasonographic detection of diaphragmatic hernia and cystic hygroma. The diagnosis was confirmed after termination of the pregnancy. The fetus also had 2 erupted incisors; natal teeth had not been mentioned in other cases of Fryns syndrome.

Differential Diagnosis:

- McPherson et al. (1993) noted the phenotypic overlap between Fryns syndrome and the Pallister–Killian syndrome (601803), which is a dysmorphic syndrome with tissue-specific mosaicism of tetrasomy 12p.

- Veldman et al. (2002) discussed the differentiation between Fryns syndrome and Pallister–Killian syndrome, noting that differentiation is important to genetic counseling because Fryns syndrome is an autosomal recessive disorder and Pallister–Killian syndrome is usually a sporadic chromosomal aberration. However, discrimination may be difficult due to the phenotypic similarity. In fact, in some infants with 'coarse face,' acral hypoplasia, and internal anomalies, the initial diagnosis of Fryns syndrome had to be changed because mosaicism of isochromosome 12p was detected in fibroblast cultures or kidney tissue. Although congenital diaphragmatic hernia is a common finding in both syndromes, bilateral congenital diaphragmatic hernia had been reported only in patients with Fryns syndrome until the report of the patient with Pallister–Killian syndrome by Veldman et al. (2002).

- Slavotinek (2004) reviewed the phenotypes of 52 reported cases of Fryns syndrome and reevaluated the diagnostic guidelines. She concluded that congenital diaphragmatic hernia and distal limb hypoplasia are strongly suggestive of Fryns syndrome, with other diagnostically relevant findings including pulmonary hypoplasia, craniofacial dysmorphism, polyhydramnios, and orofacial clefting. Slavotinek (2004) stated that other distinctive anomalies not mentioned in previous guidelines include ventricular dilatation or hydrocephalus, agenesis of the corpus callosum, abnormalities of the aorta, dilatation of the ureters, proximal thumbs, and broad clavicles.

Different types of ataxia:

- congenital ataxias (developmental disorders)

- ataxias with metabolic disorders

- ataxias with a DNA repair defect

- degenerative ataxias

- ataxia associated with other features.

The outcome of this disease is dependent on the severity of the cardiac defects. Approximately 1 in 3 children with this diagnosis require shunting for the hydrocephaly that is often a consequence. Some children require extra assistance or therapy for delayed psychomotor and speech development, including hypotonia.

Clinical diagnosis is conducted on individuals with age onset between late teens and late forties who show the initial characteristics for the recessive autosomal cerebellar ataxia.

The following tests are performed:

- MRI brain screening for cerebellum atrophy.

- Molecular genetic testing for SYNE-1 sequence analysis.

- Electrophysiologic studies for polyneurotherapy

- Neurological examination

Prenatal diagnosis and preimplantation genetic diagnosis (PGD) can be performed to identify the mothers carrying the recessive genes for cerebellar ataxia.

Radiologic osteosclerosis and histology are the main diagnostic features. Diagnosis can often be difficult because of the rareness of ECD as well as the need to differentiate it from LCH. A diagnosis from neurological imaging may not be definitive. The presence of symmetrical cerebellar and pontine signal changes on T2-weighted images seem to be typical of ECD, however, multiple sclerosis and metabolic diseases must also be considered in the differential diagnosis. ECD is not a common cause of exophthalmos but can be diagnosed by biopsy. However, like all biopsies, this may be inconclusive. Video-assisted thoracoscopic surgery may be used for diagnostic confirmation and also for therapeutic relief of recurrent pericardial fluid drainage.

Treatment is not needed in the asymptomatic patient. Symptomatic patients may benefit from surgical debulking of the tumor. Complete tumor removal is not usually needed and can be difficult due to the tumor location.

The severity of different forms of PCH varies, but many children inheriting the mutated gene responsible do not survive infancy or childhood; nevertheless, some individuals born with PCH have reached adulthood.

When it comes to treatment it is important to differentiate a thumb that needs stability, more web width and function, or a thumb that needs to be replaced by the index finger. Severe thumb hypoplasia is best treated by pollicization of the index finger. Less severe thumb hypoplasia can be reconstructed by first web space release, ligament reconstruction and muscle or tendon transfer.

It has been recommended that pollicization is performed before 12 months, but a long-term study of pollicizations performed between the age of 9 months and 16 years showed no differences in function related to age at operation.

It is important to know that every reconstruction of the thumb never gives a normal thumb, because there is always a decline of function. When a child has a good index finger, wrist and fore-arm the maximum strength of the thumb will be 50% after surgery in comparison with a normal thumb. The less developed the index finger, wrist and fore-arm is, the less strength the reconstructed thumb will have after surgery.

Histologically, ECD differs from Langerhans cell histiocytosis (LCH) in a number of ways. Unlike LCH, ECD does not stain positive for S-100 proteins or Group 1 CD1a glycoproteins, and electron microscopy of cell cytoplasm does not disclose Birbeck granules. Tissue samples show xanthomatous or xanthogranulomatous infiltration by lipid-laden or foamy histiocytes, and are usually surrounded by fibrosis. Bone biopsy is said to offer the greatest likelihood of reaching a diagnosis. In some, there is histiocyte proliferation, and on staining, the section is CD68+ and CD1a-.

In terms of the diagnosis of adenylosuccinate lyase deficiency one should look for (or exam/method):

- MRI

- Demonstration of Succinylpurines in extracellular fluids like plasma, cerebrospinal fluid (CSF) and/or urine using HPLC or HPLC-MS

- Genetic testing - genomic cDNA sequencing of the ADSL gene and characterization of mutant proteins.

Lhermitte–Duclos disease is a rare entity; approximately 222 cases of LDD have been reported in medical literature. Symptoms of the disease most commonly manifest in the third and fourth decades of life, although it may onset at any age. Men and women are equally affected, and there is not any apparent geographical pattern.

Although there is no cure for 13q deletion syndrome, symptoms can be managed, usually with the involvement of a neurologist, rehabilitation physician, occupational therapist, physiotherapist, psychotherapist, nutritionist, special education professional, and/or speech therapist. If the affected child's growth is particularly slow, growth hormone treatment can be used to augment growth. Plastic surgeries can repair cleft palates, and surgical repair or monitoring by a pediatric cardiologist can manage cardiac defects. Some skeletal, neurological, genitourinary, gastrointestinal, and ophthalmic abnormalities can be definitively treated with surgery. Endocrine abnormalities can often be managed medically. Special educators, speech and occupational therapists, and physiotherapists can help a child develop skills in and out of school.

Molecular (DNA) testing for PAX6 gene mutations (by sequencing of the entire coding region and deletion/duplication analysis) is available for isolated aniridia and the Gillespie syndrome. For the WAGR syndrome, high-resolution cytogenetic analysis and fluorescence in situ hybridization (FISH) can be utilized to identify deletions within chromosome band 11p13, where both the PAX6 and WT1 genes are located.

VLDLR-associated cerebellar hypoplasia (VLDLRCH; alternative names: dysequilibrium syndrome, DES; nonprogressive cerebellar disorder with mental retardation) is a rare autosomal recessive condition caused by a disruption of the VLDLR gene. First described as a form of cerebral palsy in the 1970s, it is associated with parental consanguinity and is found in secluded communities, with a number of cases described in Hutterite families.