Affected newborns generally have striking neurological defects and seizures. Severely impaired development is common, but disturbances in motor functions may not appear until later in life.

Infants with microcephaly are born with either a normal or reduced head size. Subsequently, the head fails to grow, while the face continues to develop at a normal rate, producing a child with a small head and a receding forehead, and a loose, often wrinkled scalp. As the child grows older, the smallness of the skull becomes more obvious, although the entire body also is often underweight and dwarfed. Development of motor functions and speech may be delayed. Hyperactivity and intellectual disability are common occurrences, although the degree of each varies. Convulsions may also occur. Motor ability varies, ranging from in some to spastic quadriplegia in others.

BFPP is a cobblestone-like cortical malformation of the brain. Disruptions of cerebral cortical development due to abnormal neuronal migration and positioning usually lead to cortical disorders, which includes cobblestone lissencephaly. Cobblestone lissencephaly is typically seen in three different human congenital muscular dystrophy syndromes: Fukuyama congenital muscular dystrophy, Walker-Warburg syndrome, and muscle-eye-brain disease. In cobblestone lissencephaly, the brain surface actually has a bumpy contour caused by the presence of collections of misplaced neurons and glial cells that have migrated beyond the normal surface boundaries of the brain. Sometimes regions populated by these misplaced cells have caused a radiologic misdiagnosis of polymicrogyria. However, the presence of other abnormalities in these cobblestone lissencephaly syndromes, including ocular anomalies, congenital muscular dystrophy, ventriculomegaly, and cerebellar dysplasia, usually distinguishes these disorders from polymicrogyria. There are no anatomopathologic studies that have characterized the pattern of cortical laminar alterations in patients with GPR56 gene mutations, but it has been suggested that the imaging characteristics of BFPP, including myelination defects and cerebellar cortical dysplasia, are reminiscent of those of the so-called cobblestone malformations (muscle-eye-brain disease and Fukuyama congenital muscular dystrophy) that are also associated with N-glycosylation defects in the developing brain.

Lissencephaly ("smooth brain") is the extreme form of pachygyria. In lissencephaly, few or no sulci are seen on the cortical surface, resulting in a broad, smooth appearance to the entire brain. Lissencephaly can be radiologically confused with polymicrogyria, particularly with low-resolution imaging, but the smoothness and lack of irregularity in the gray-white junction, along with markedly increased cortical thickness, distinguishes lissencephaly.

GPR56 mutation also can cause a severe encelphalopathy which is associated with electro clinical features of the Lennox-Gastaut syndrome. Lennox-Gastaut syndrome can be cryptogenic or symptomatic, but the symptomatic forms have been associated with multiple etiologies and abnormal cortical development. BFPP caused by GPR56 mutations is a representation of a malformation of cortical development that causes Lennox-Gastaut Syndrome.

Polymicrogyria usually gets misdiagnose with pacygyria so therefore it needs to be distinguished from pachygyria. Pachygyria is a distinct brain malformation in which the surface folds are excessively broad and sparse. Pachygyria and polymicrogyria may look similar on low-resolution neuroimaging such as CT because the cortical thickness can appear to be increased and the gyri can appear to be broad and smooth in both conditions. This is why higher resolution neuroimaging are needed such as an MRI.

Microcephaly is a medical condition in which the brain does not develop properly resulting in a smaller than normal head. Microcephaly may be present at birth or it may develop in the first few years of life. Often people with the disorder have an intellectual disability, poor motor function, poor speech, abnormal facial features, seizures, and dwarfism.

The disorder may stem from a wide variety of conditions that cause abnormal growth of the brain, or from syndromes associated with chromosomal abnormalities. A homozygous mutation in one of the "microcephalin" genes causes primary microcephaly. It serves as an important neurological indication or warning sign, but no uniformity exists in its definition. It is usually defined as a head circumference (HC) more than two standard deviations below the mean for age and sex. Some academics advocate defining it as head circumference more than three standard deviations below the mean for the age and sex.

There is no specific treatment that returns the head size to normal. In general, life expectancy for individuals with microcephaly is reduced and the prognosis for normal brain function is poor. Occasionally, some will grow normally and develop normal intelligence.

Microlissencephalic patients suffer from spasticity, seizures, severe developmental delay and intellectual disabilities with survival varying from days to years. Patients may also have dysmorphic craniofacial features, abnormal genitalia, and arthrogryposis.

Microlissencephaly may arise as a part of Baraitser-Winter syndrome which comprises also ptosis, coloboma, hearing loss and learning disability.

Moreover, it is the distinct developmental brain abnormality in "microcephalic osteodysplastic primordial dwarfism" (MOPD1). Microlissencephaly may be accompanied by micromelia as in Basel-Vanagaite-Sirota syndrome ( Microlissencephaly-Micromelia syndrome).

Microlissencephaly Type B or Barth microlissencephaly syndrome: is a microlissencephaly with thick cortex, severe cerebellar and brainstem hypoplasia. The Barth-type of MLIS is the most severe of all the known lissencephaly syndromes.

This phenotype consists of polyhydramnios (probably due to poor fetal swallowing), severe congenital microcephaly, weak respiratory effort, and survival for only a few hours or days. Barth described two siblings with this type as having a very low brainweight, wide ventricles, a very thin neopallium, absent corpus callosum and absent olfactory nerve.

There are different tests or methods used to determine GPR56 expression or visuals of the brain to analyze the specific sections that are affected. These tests for example, using animals such as mice, RNAi, Behavioral assay, Electron microscopy, CT scan, or MRI demonstrate different results that concludes an affected BFPP patient. MRI's reveal either irregularity to the cortical surface suggestive of multiple small folds or an irregular, scalloped appearance of the gray matter-white matter junction.

Neuroimaging The diagnosis of polymicrogyria is typically made by magnetic resonance imaging (MRI) since computed tomography (CT) and other imaging methods generally do not have high enough resolution or adequate contrast to identify the small folds that define the condition. The cerebral cortex often appears abnormally thick as well because the multiple small gyri are fused, infolded, and superimposed in appearance.

Neuropathology Gross neuropathologic examination reveals a pattern of complex convolutions to the cerebral cortex, with miniature gyri fused and superimposed together, often resulting in an irregular brain surface. The cortical ribbon can appear excessively thick as a result of the infolding and fusion of multiple small gyri.

Microscopic examination demonstrates that the cerebral cortex is in fact abnormally thin and has abnormal lamination; typically the cortex is unlayered or has four layers, in contrast to the normal six layers. The most superficial layers between adjacent small gyri appear fused, with the pia (layer of the meninges) bridging across multiple gyri. Prenatal diagnosis for BFPP is also available for pregnancies at risk if the GPR56 mutations have been identified in an affected family member.

The specific problems produced differ according to the particular abnormal synthesis involved. Common manifestations include ataxia; seizures; retinopathy; liver fibrosis; coagulopathies; failure to thrive; dysmorphic features ("e.g.," inverted nipples and subcutaneous fat pads; and strabismus. If an MRI is obtained, cerebellar atrophy and hypoplasia is a common finding.

Ocular abnormalities of CDG-Ia include: myopia, infantile esotropia, delayed visual maturation, low vision, optic disc pallor, and reduced rod function on electroretinography.

Three subtypes of CDG I (a,b,d) can cause congenital hyperinsulinism with hyperinsulinemic hypoglycemia in infancy.

Symptoms of congenital Type III Galactosemia are apparent from birth, but vary in severity depending on whether the peripheral or generalized disease form is present. Symptoms may include:

- Infantile jaundice

- Infantile hypotonia

- Dysmorphic features

- Sensorineural hearing loss

- Impaired growth

- Cognitive deficiencies

- Depletion of cerebellar Purkinje cells

- Ovarian failure (POI) and hypertrophic hypergonadism

- Liver failure

- Renal failure

- Splenomegaly

- Cataracts

Studies of Type III galactosemia symptoms are mostly descriptive, and precise pathogenic mechanisms remain unknown. This is largely due to a lack of functional animal models of classic galactosemia. The recent development of a "Drosophila melanogaster" GALE mutant exhibiting galactosemic symptoms may yield a promising future animal model.

Mutations in several genes have been associated with the traditional clinical syndromes, termed muscular dystrophy-dystroglycanopathies (MDDG). A new nomenclature based on clinical severity and genetic cause was recently proposed by OMIM. The severity classifications are A (severe), B (intermediate), and C (mild). The subtypes are numbered one to six according to the genetic cause, in the following order: (1) POMT1, (2) POMT2, (3) POMGNT1, (4) FKTN, (5) FKRP, and (6) LARGE.

Most common severe types include:

In terms of the signs/symptoms of Fukuyama congenital muscular dystrophy it is characterized by a decrease in skeletal muscle tone as well as an impairment in brain and eye development.Initial symptoms of FCMD present in early infancy as decreased ability to feed. Marked differences in facial appearance occur due to decreased muscle tone. Further characteristics include:

- Seizures

- Delay in developmental

- Cardiac issues

- Swallowing difficulty

- Neurological problems

Fukuyama congenital muscular dystrophy also affects the nervous system and various associated parts. FCMD affects normal development of the brain producing a broadly smooth, bumpy shaped cortex named cobblestone lissencephaly as well as various other malformations, notably micropolygyria. Children also experience delayed myelination in the brain.

CCD causes persistent secretory diarrhea. In a fetus, it leads to polyhydramnios and premature birth. Immediately after birth, it leads to dehydration, hypoelectrolytemia, hyperbilirubinemia, abdominal distention, and failure to thrive.

EEM syndrome exhibits a combination of prominent symptoms and features. These include: ectodermal dysplasia (systemic malformations of ectodermal tissues), ectrodactyly ("lobster claw" deformity in the hands and feet), macular dystrophy (a progressive eye disease), syndactyly (webbed fingers or toes), hypotrichosis (a type of hair-loss), and dental abnormalities (hypodontia).

CIE has symptoms very similar to Lamellar ichthyosis (LI) but milder and is considered by many scientists to be a variant of that disease, so both diseases are grouped under the title autosomal recessive congenital ichthyosis (ARCI).

The baby is often born in a collodion membrane, a shiny, wax outer layer on the skin and usually with ectropion, having the lower eyelid turned outwards. When the membrane is shed the skin is red with a generalized white scale. Palms, soles and areas on the joints are often affected with hyperkeratosis, a thickening of the layer of dead skin cells on the surface of the skin. In classical CIE (unlike LI) there is little eclabion (eversion of the lips), ectropion and alopecia (hair loss).

Many people with ACRI don't fit neatly into the definition of LI or CIE but have characteristics of both diseases. The definitions of CIE and LI describe the extremes of the range of ACRI.

Manifestations include enlarged viscera, hepatomegaly, diabetes, short stature and cranial hyperostosis.

Fukuyama congenital muscular dystrophy (FCMD) is a rare, autosomal recessive form of muscular dystrophy (weakness and breakdown of muscular tissue) mainly described in Japan but also identified in Turkish and Ashkenazi Jewish patients, fifteen cases were first described on 1960 by Fukuyama.

FCMD mainly affects the brain, eyes, and muscles, in particular, the disorder affects development of the skeletal muscles leading to weakness and deformed appearances, and brain development is blunted affecting cognitive functioning as well as social skills. In 1995, the disorder was linked to mutations in a gene coding for the protein fukutin (the "FCMD" gene). Fukuyama congenital muscular dystrophy is the second most prevalent form of muscular dystrophy in Japan. One out of every 90 people in Japan is a heterozygous carrier.

HIES often appears early in life with recurrent staphylococcal and candidal infections, pneumonias, and eczematoid skin.

- Autosomal dominant Hyper-IgE Syndrome caused by STAT3 defects, called Job Syndrome, have characteristic facial, dental, and skeletal abnormalities. Patients with STAT3 HIES may have either delay of or failure in shedding of primary teeth. The characteristic facial features are usually set by age 16. These include facial asymmetry, a prominent forehead, deep-set eyes, a broad nasal bridge, a wide, fleshy nasal tip, and mild prognathism. Additionally, facial skin is rough with prominent pores. Finally, some patients with STAT3 HIES have scoliosis, as well as bones that fracture easily.

- Autosomal recessive

Aplasia cutis congenita (ACC) is a rare disorder characterized by congenital absence of skin. Frieden classified ACC in 1986 into 9 groups on the basis of location of the lesions and associated congenital anomalies. The scalp is the most commonly involved area with lesser involvement of trunk and extremities. Frieden classified ACC with fetus papyraceus as type 5. This type presents as truncal ACC with symmetrical absence of skin in stellate or butterfly pattern with or without involvement of proximal limbs.]It is the most common congenital cicatricial alopecia, and is a congenital focal absence of epidermis with or without evidence of other layers of the skin.

The exact etiology of ACC is still unclear but intrauterine infection by varicella or herpes virus, drugs such as methimazole, misoprostol, valproate, cocaine, marijuana etc., fetus papyraceus, feto-fetal transfusion, vascular coagulation defects, amniotic membrane adherence, abnormal elastic fiber biomechanical forces and trauma are implicated. It can be associated with Johanson-Blizzard syndrome, Adams-Oliver syndrome, trisomy 13, and Wolf-Hirschhorn syndrome.

It can also seen with exposure to methimazole and carbimazole in utero. This dermatological manifestation has been linked to Peptidase D haploinsufficiency and a deletion in Chromosome 19.

Katz Syndrome is a rare congenital disorder, presenting as a polymalformative syndrome characterized by enlarged viscera, hepatomegaly, diabetes, and skeletal anomalies that result in a short stature, cranial hyperostosis, and typical facial features. It is probably a variant of the autosomal recessive type of Craniometaphyseal Dysplasia.

Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder which manifests with insulin resistance, absence of subcutaneous fat and muscular hypertrophy. Homozygous or compound heterozygous mutations in four genes are associated with the four subtypes of CGL. The condition appears in early childhood with accelerated linear growth, quick aging of bones, and a large appetite. As the child grows up, acanthosis nigricans (hyperpigmentation and thickening of skin) will begin to present itself throughout the body – mainly in the neck, trunk, and groin. The disorder also has characteristic features like hepatomegaly or an enlarged liver which arises from fatty liver and may lead to cirrhosis, muscle hypertrophy, lack of adipose tissue, splenomegaly, hirsutism (excessive hairiness) and hypertriglyceridemia. Fatty liver and muscle hypertrophy arise from the fact that lipids are instead stored in these areas; whereas in a healthy individual, lipids are distributed more uniformly throughout the body subcutaneously. The absence of adipose tissue where they normally occur causes the body to store fat in the remaining areas. Common cardiovascular problems related to this syndrome are cardiac hypertrophy and arterial hypertension (high blood pressure). This disorder can also cause metabolic syndrome. Most with the disorder also have a prominent umbilicus or umbilical hernia. Commonly, patients will also have acromegaly with enlargement of the hands, feet, and jaw. After puberty, additional symptoms can develop. In women, clitoromegaly and polycystic ovary syndrome can develop. This impairs fertility for women, and only a few documented cases of successful pregnancies in women with CGL exist. However, the fertility of men with the disorder is unaffected.

Galactose epimerase deficiency, also known as GALE deficiency, Galactosemia III and UDP-galactose-4-epimerase deficiency, is a rare, autosomal recessive form of galactosemia associated with a deficiency of the enzyme "galactose epimerase".

Congenital Ichthyosiform Erythroderma (CIE), also known as Nonbullous congenital ichthyosiform erythroderma is a rare type the ichthyosis family of skin diseases which occurs in 1 in 200,000 to 300,000 births.

Symptoms may differ greatly, as apparently modifiers control to some degree the amount of FX that is produced. Some affected individuals have few or no symptoms while others may experience life-threatening bleeding. Typically this bleeding disorder manifests itself as a tendency to easy bruising, nose bleeding, heavy and prolonged menstruation and bleeding during pregnancy and childbirth, and excessive bleeding after dental or surgical interventions. Newborns may bleed in the head, from the umbilicus, or excessively after circumcision. Other bleeding can be encountered in muscles or joints, brain, gut, or urine

While in congenital disease symptoms may be present at birth or show up later, in patients with acquired FX deficiency symptoms typically show up in later life.

The primary malformation apparent with JBS is hypoplasia (underdevelopment) of the nasal alae, or "wing of the nose". Both hypoplasia and aplasia (partial or complete absence) of structural cartilage and tissue in this area of the nose, along with the underlying alae nasi muscle, are prevailing features of the disorder. Together, these malformations give the nose and nostrils an odd shape and appearance.

CCD may be detectable on prenatal ultrasound. After birth, signs in affected babies typically are abdominal distension, visible peristalsis, and watery stools persistent from birth that show chloride loss of more than 90 mmol/l.

An important feature in this diarrhea that helps in the diagnosis, is that it is the only type of diarrhea that causes metabolic alkalosis rather than metabolic acidosis.

It is characterized by recurrent "cold" staphylococcal infections, unusual eczema-like skin rashes, severe lung infections that result in pneumatoceles (balloon-like lesions that may be filled with air or pus or scar tissue) and very high concentrations of the serum antibody IgE. Inheritance can be autosomal dominant or autosomal recessive. Many patients with autosomal dominant STAT3 hyper-IgE syndrome have characteristic facial and dental abnormalities, fail to lose their primary teeth, and have two sets of teeth simultaneously.