Orofaciodigital syndrome type 14 is a rare subtype of orofaciodigital syndrome, with autosomal recessive inheritance and C2CD3 mutations, characterized by severe microcephaly, trigonocephaly, severe intellectual disability and micropenis, in addition to oral, facial and digital malformations (gingival frenulae, lingual hamartomas, cleft/lobulated tongue, cleft palate, telecanthus, up-slanting palpebral fissures, microretrognathia, postaxial polydactyly of hands and duplication of hallux). Corpus callosum agenesis and vermis hypoplasia with molar tooth sign, on brain imaging, are also associated.

All 3 had the same heterozygous missense mutation: a G-to-T change affecting the first nucleotide at codon 32 (116806.0016).

Pilomatrixoma is a rare and benign hair cell-derived tumor occurring mostly in young adults (usually under the age of 20) and characterized as a 3-30 mm solitary, painless, firm, mobile, deep dermal or subcutaneous tumor, most commonly found in the head, neck or upper extremities. When superficial, the tumors tint the skin blue-red. Multiple pilomatrixomas are seen in myotonic dystrophy, Gardner syndrome, Rubinstein-Taybi syndrome, and Turner syndrome (see these terms).

Pilomatricoma, also known as pilomatrixoma, is a type of noncancerous (benign) skin tumor associated with hair follicles. Hair follicles are specialized structures in the skin where hair growth occurs. Pilomatricomas occur most often on the head or neck, although they can also be found on the arms, torso, or legs. A pilomatricoma feels like a small, hard lump under the skin. This type of tumor grows relatively slowly and usually does not cause pain or other symptoms. Most affected individuals have a single tumor, although rarely multiple pilomatricomas can occur.

Pilomatrixoma is a benign (non-cancerous) skin tumor of the hair follicle (structure in the skin that makes hair). They tend to develop in the head and neck area and are usually not associated with any other signs and symptoms (isolated). Rarely, pilomatrixomas can become cancerous (known as a pilomatrix carcinoma). Although they can occur in people of all ages, pilomatrixomas are most commonly diagnosed in people under age 20. The exact underlying cause is not well understood; however, somatic changes (mutations) in the CTNNB1 gene are found in most isolated pilomatrixomas.

Infantile myofibromatosis Other names Congenital generalized fibromatosis, [1] and Congenital multicentric fibromatosis [1] Specialty Oncology Infantile myofibromatosis is the most common fibrous tumor of infancy, in which eighty percent of patients have solitary lesions with half of these occurring on the head and neck, and 60% are present at or soon after birth. [2] : 606 Less commonly, infantile myofibromatosis presents as multiple lesions of skin, muscle, and bone with about 1/3 of these cases also having lesions in their visceral organs. All of these cases have an excellent prognosis with their tumors sometimes regressing spontaneously except for those cases in which there is visceral involvement where the prognosis is poor. [3] Infantile myofibromatosis and the classic form of mesoblastic nephroma have been suggested to be the same disease because of their very similar histology. However, studies on the distribution of cell-type markers (i.e. cyclin D1 and Beta-catenin ) indicate that the two neoplasms likely have different cellular origins. [4] [5] See also [ edit ] Skin lesion List of cutaneous conditions mesoblastic nephroma References [ edit ] ^ a b Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set . St. Louis: Mosby. ISBN 978-1-4160-2999-1 . ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology . (10th ed.). Saunders.

In cases of familial and multifocal lesions, IM can be inherited as an autosomal recessive or dominant trait (incomplete penetrance and variable expressivity).

Inheritance The transmission pattern of IMF2 in the family reported by Martignetti et al. (2013) was consistent with autosomal dominant inheritance. Molecular Genetics In affected members of a family with IMF2, Martignetti et al. (2013) identified a heterozygous mutation in the NOTCH3 gene (L1519P; 600276.0012). ... No functional studies were performed, but the authors predicted that the mutation would result in hyperactivation of NOTCH3. INHERITANCE - Autosomal dominant MUSCLE, SOFT TISSUES - Myofibromatosis MISCELLANEOUS - Onset in infancy or early childhood - One family has been reported and no additional clinical features were provided (last curated June 2013) MOLECULAR BASIS - Caused by mutation in the homolog of the Drosophila NOTCH, 3, gene (NOTCH3, 600276.0012 ) ▲ Close

A rare ciliopathy characterized by congenital cataract with secondary glaucoma, developmental delay, short stature, multiple skeletal abnormalities (spinal deformities, limb anomalies, delayed bone age), dental anomalies (oligodontia, enamel defects), dysmorphic facial features (including coarse facies, low hairline, epicanthal folds, flat and broad nasal bridges, and retrognathia), and stroke. Other recurrent manifestations are hearing loss and nephrocalcinosis.

Severe dermatitis-multiple allergies-metabolic wasting syndrome is a rare, genetic, epidermal disorder characterized by congenital erythroderma with severe psoriasiform dermatitis, ichthyosis, severe palmoplantar keratoderma, yellow keratosis on the hands and feet, elevated immunoglobulin E, multiple food allergies, and metabolic wasting. Other variable features may include hypotrichosis, nail dystrophy, recurrent infections, mild global developmental delay, eosinophillia, nystagmus, growth impairment and cardiac defects.

A rare genetic disease characterized by co-occurrence of sick sinus syndrome (manifesting as sinus bradycardia, often requiring pacemaker implantation) and chronic intestinal pseudo-obstruction (which may be of myogenic or neurogenic origin and usually requires total parenteral nutrition), with an age of onset within the first four decades of life. Other cardiac features, such as atrial flutter or fibrillation and valve anomalies, may also be present.

Chronic atrial and intestinal dysrhythmia (CAID) is a disorder affecting the heart and the digestive system. CAID disrupts the normal rhythm of the heartbeat ; affected individuals have a heart rhythm abnormality called sick sinus syndrome. The disorder also impairs the rhythmic muscle contractions that propel food through the intestines (peristalsis), causing a digestive condition called intestinal pseudo-obstruction. The heart and digestive issues develop at the same time, usually by age 20. Sick sinus syndrome (also known as sinus node dysfunction) is an abnormality of the sinoatrial (SA) node, which is an area of specialized cells in the heart that functions as a natural pacemaker.

Lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome is rare, genetic, neurometabolic disease characterized by global developmental delay, severe hypotonia, seizures, cataracts, cardiomyopathy (including left or bi-ventricular hypertrophy, dilated cardiomyopathy) and left ventricular non-compaction, typically resulting in infantile or early-childhood death. Patients usually present metabolic lactic acidosis, failure to thrive, head lag, respiratory problems and decrease in respiratory chain complex activity. Highly variable cerebral abnormalities have been reported and include microcephaly, prominent extra-axial cerebrospinal fluid spaces, diffuse neuronal loss and cortical/white matter gliosis.

A subtype of Charcot-Marie-Tooth disease type 4 characterized by childhood onset of severe, progressive, demyelinating sensorimotor neuropathy manifesting with distal muscle weakness and atrophy of hands and feet, distal sensory impairment (vibration and pinprick) of lower limbs, lactic acidosis, areflexia and severely reduced motor nerve conduction velocities (25 m/s or less). Patients may also present kyphoscoliosis, nystagmus, hearing loss, cerebellar ataxia and/or brain MRI abnormalities (putaminal and periaqueductal lesions).

Variable skin manifestations include heliotrope-like rash on eyelids, nodular episcleritis, ear and nose chondritis, plantar hyperkeratosis, hyperhidrosis of hands and feet. Lipodystrophy is first noted in the face and upper limbs, giving a characteristic thin and angular facial appearance, and may become generalized to include the abdomen and lower limbs. ... Joint contractures affect mainly the hands and feet at first but can later spread to other joints and can cause pain and joint deformities.

The patients carried a heterozygous nonsense mutation in the PSMB4 gene (Y222X; 602177.0001) on 1 allele and a missense mutation in the PSMB8 gene (K105Q; 177046.0005) on the other allele. The patients presented in the first 3 to 4 weeks of life with skin lesions, fever, and anemia. ... The patients had previously been reported as patients 7 and 9 by Liu et al. (2012), who identified a heterozygous missense mutation in the PRMB8 gene (T75M; 177046.0001) in both patients, but a second mutation could not be found. Using a combination of whole-exome sequencing and screening of proteasomal candidate genes in these patients, Brehm et al. (2015) found that these patients carried a heterozygous mutation in the PSMA3 gene (176843.0001 and 176843.0002, respectively) on 1 allele and the common heterozygous heterozygous T75M missense mutation in the PSMB8 gene on the other allele. ... The patients had onset of symptoms in the first months of life. Features were somewhat variable, but included periorbital erythema and edema, violaceous eyelids, fever, skin lesions, myositis, arthralgia, joint contracture, increased acute phase reactants, lymphadenopathy, lipodystrophy, and poor overall growth. ... INHERITANCE - Autosomal recessive GROWTH Height - Short stature (less common) Other - Failure to thrive - Poor growth HEAD & NECK Face - Loss of facial subcutaneous fat - Periorbital swelling due to violaceous plaques on the eyelids Eyes - Conjunctivitis - Episcleritis Mouth - Macroglossia - Thick lips CARDIOVASCULAR Heart - Cardiac insufficiency (in some) - Arrhythmias (in some) ABDOMEN - Prominent abdomen Liver - Hepatomegaly Spleen - Splenomegaly (variable) SKELETAL - Joint contractures - Narrowing of the joint spaces - Periarticular osteopenia - Bone pain - Joint pain Limbs - Elbow contractures Hands - Finger contractures, severe - Hand contractures, severe - Clubbed fingers - Long fingers - Finger deformities - Finger swelling Feet - Toe contractures, severe - Foot contractures, severe SKIN, NAILS, & HAIR Skin - Erythematous nodular skin lesions - Annular erythematous edematous plaques - Lesions become purpuric - Residual hyperpigmentation - Lesions predominantly on face and limbs - Panniculitis - Dry, stiff skin - Frostbitten hands Skin Histology - Mononuclear cell infiltrates - Atypical mononuclear cells with many mitoses MUSCLE, SOFT TISSUES - Lipodystrophy, partial - Lipodystrophy, generalized, panniculitis-induced (in some) - Marked loss of subcutaneous fat in the limbs, face, and sometimes chest - Muscle atrophy (variable) - Muscle weakness NEUROLOGIC Central Nervous System - Mental retardation, mild (2 families) - Seizures (uncommon) - Basal ganglia calcification METABOLIC FEATURES - Fever, intermittent, recurrent (in some) HEMATOLOGY - Microcytic anemia - Thrombocytopenia IMMUNOLOGY - Antinuclear autoantibodies (in some) - Lymphadenopathy LABORATORY ABNORMALITIES - Increased erythrocyte sedimentation rate - Hypergammaglobulinemia - Increased gamma-interferon - Increased IgG - Increased IgA - Increased IL-6 - Increased IL-8 - Increased C-reactive protein - Abnormal liver enzymes, intermittent - Increased serum triglycerides MISCELLANEOUS - Onset of autoinflammation in infancy or first few years of life - Onset of lipodystrophy later in childhood - Onset of joint contractures later in life - Some features are variable MOLECULAR BASIS - Caused by mutation in the proteasome subunit, beta-type, 8 gene (PSMB8, 177046.0001 ) ▲ Close

Nakajo-Nishimura syndrome is an inherited condition that affects many parts of the body and has been described only in the Japanese population. Beginning in infancy or early childhood, affected individuals develop red, swollen lumps (nodular erythema) on the skin that occur most often in cold weather; recurrent fevers; and elongated fingers and toes with widened and rounded tips (clubbing). Later in childhood, affected individuals develop joint pain and joint deformities called contractures that limit movement, particularly in the hands, wrists, and elbows. They also experience weakness and wasting of muscles, along with a loss of fatty tissue (lipodystrophy), mainly in the upper body. The combination of muscle and fat loss worsens over time, leading to an extremely thin (emaciated) appearance in the face, chest, and arms.

Symptoms usually develop within the first few months of life and may include recurrent fevers and purple colored spots on the skin particularly around the eyes. ... It is usually inherited in an autosomal recessive pattern; however, when associated with variants in the POMP gene, may be inherited in an autosomal dominant pattern. There is no specific treatment for this condition; however, steroids may help reduce the frequency of symptoms.

Specialty Medical genetics Nakajo syndrome , also called nodular erythema with digital changes , [1] is a rare autosomal recessive congenital disorder first reported in 1939 by A. Nakajo in the offspring of consanguineous (blood relative) parents. [2] [3] The syndrome can be characterized by erythema (reddened skin), loss of body fat in the upper part of the body, and disproportionately large eyes, ears, nose, lips, and fingers. [1] Contents 1 Genetics 2 Diagnosis 3 Treatment 4 References 5 External links Genetics [ edit ] Nakajo syndrome is inherited in an autosomal recessive manner. [3] This means the defective gene responsible for the disorder is located on an autosome , and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder.