Aneurysmal bone cysts are benign primary or secondary lesions that are rapidly expansive and locally destructive. They are located in the posterior elements of the vertebral column or the flat or long bones of patients under 30 years of age. The cysts are blood-filled and separated by septa containing spindle cells, trabeculae of bone, and osteoclastic giant cells (Biesecker et al., 1970). Histopathologically and radiographically, aneurysmal bone cysts are similar to telangiectactic osteosarcoma from which they must be differentiated. Panoutsakopoulos et al. (1999) described 3 cases of aneurysmal bone cysts with chromosomal anomalies; 16q22 was involved in all 3 patients and 2 of them had a recurrent t(16;17)(q22;p13).
A rare bone tumor characterized by a benign, cystic lesion consisting of blood-filled cavities divided by fibrous septa containing fibroblasts, multinucleated osteoclast-type giant cells, and reactive woven bone. The tumor may arise de novo or secondarily, complicating other benign or malignant bone tumors. It most commonly arises during the first two decades of life and often affects the epiphyses of long bones and posterior elements of vertebral bodies. Patients typically present with pain and swelling, or neurological symptoms due to compression of nerve roots or the spinal cord by vertebral tumors.
In rare cases such as Chédiak–Higashi syndrome , albinism may be associated with deficiencies in the transportation of melanin granules. ... Ikponwosa Ero , who is from Nigeria, as the very first Independent Expert on the enjoyment of human rights by persons with albinism. [39] See also [ edit ] Albinism–deafness syndrome Marie Antoinette syndrome Dyschromia Erythrism , unusually red pigmentation Heterochromia iridum Human variability Isabellinism Nevus , or birthmark Piebaldism , patchy alternating loss of and concentrations of dermal pigmentation Vitiligo (or leukoderma), patchy loss of dermal pigmentation Xanthochromism and axanthism , unusually yellow pigmentation and lack of yellow pigment, respectively References [ edit ] ^ "albino" . ... Retrieved 10 November 2017 . ^ Kaplan, J.; De Domenico, I.; Ward, D. M. (2008). "Chediak-Higashi syndrome". Current Opinion in Hematology . 15 (1): 22–29. doi : 10.1097/MOH.0b013e3282f2bcce . ... Retrieved January 27, 2015 . ^ Tietz, W. (1963). "A Syndrome of Deaf-Mutism Associated with Albinism Showing Dominant Autosomal Inheritance" . ... Skeptoid . v t e Pigmentation disorders / Dyschromia Hypo- / leucism Loss of melanocytes Vitiligo Quadrichrome vitiligo Vitiligo ponctué Syndromic Alezzandrini syndrome Vogt–Koyanagi–Harada syndrome Melanocyte development Piebaldism Waardenburg syndrome Tietz syndrome Loss of melanin / amelanism Albinism Oculocutaneous albinism Ocular albinism Melanosome transfer Hermansky–Pudlak syndrome Chédiak–Higashi syndrome Griscelli syndrome Elejalde syndrome Griscelli syndrome type 2 Griscelli syndrome type 3 Other Cross syndrome ABCD syndrome Albinism–deafness syndrome Idiopathic guttate hypomelanosis Phylloid hypomelanosis Progressive macular hypomelanosis Leukoderma w/o hypomelanosis Vasospastic macule Woronoff's ring Nevus anemicus Ungrouped Nevus depigmentosus Postinflammatory hypopigmentation Pityriasis alba Vagabond's leukomelanoderma Yemenite deaf-blind hypopigmentation syndrome Wende–Bauckus syndrome Hyper- Melanin / Melanosis / Melanism Reticulated Dermatopathia pigmentosa reticularis Pigmentatio reticularis faciei et colli Reticulate acropigmentation of Kitamura Reticular pigmented anomaly of the flexures Naegeli–Franceschetti–Jadassohn syndrome Dyskeratosis congenita X-linked reticulate pigmentary disorder Galli–Galli disease Revesz syndrome Diffuse/ circumscribed Lentigo / Lentiginosis : Lentigo simplex Liver spot Centrofacial lentiginosis Generalized lentiginosis Inherited patterned lentiginosis in black persons Ink spot lentigo Lentigo maligna Mucosal lentigines Partial unilateral lentiginosis PUVA lentigines Melasma Erythema dyschromicum perstans Lichen planus pigmentosus Café au lait spot Poikiloderma ( Poikiloderma of Civatte Poikiloderma vasculare atrophicans ) Riehl melanosis Linear Incontinentia pigmenti Scratch dermatitis Shiitake mushroom dermatitis Other/ ungrouped Acanthosis nigricans Freckle Familial progressive hyperpigmentation Pallister–Killian syndrome Periorbital hyperpigmentation Photoleukomelanodermatitis of Kobori Postinflammatory hyperpigmentation Transient neonatal pustular melanosis Other pigments Iron Hemochromatosis Iron metallic discoloration Pigmented purpuric dermatosis Schamberg disease Majocchi's disease Gougerot–Blum syndrome Doucas and Kapetanakis pigmented purpura / Eczematid-like purpura of Doucas and Kapetanakis Lichen aureus Angioma serpiginosum Hemosiderin hyperpigmentation Other metals Argyria Chrysiasis Arsenic poisoning Lead poisoning Titanium metallic discoloration Other Carotenosis Tar melanosis Dyschromia Dyschromatosis symmetrica hereditaria Dyschromatosis universalis hereditaria See also Skin color Skin whitening Tanning Sunless Tattoo removal Depigmentation v t e Human skin color Albino (I.)
Langer et al. (1983) reported a single case of a Japanese infant who died in the newborn period of cardiac and renal failure. X-rays showed bizarre deformities of the forearm and lower leg. The corneas were clouded and the kidneys enlarged. Renal biopsies showed glomerulocystic kidneys. A noncyanotic cardiac malformation was thought to be present. Autopsy was refused. The parents were apparently unrelated--mother aged 31 and father aged 36. INHERITANCE - Isolated cases HEAD & NECK Face - Micrognathia Ears - Low-set ears - Prominent lobules Eyes - Short palpebral fissures - Corneal opacities Nose - Depressed nasal bridge GENITOURINARY Kidneys - Glomerulocystic dysplasia - Renal failure SKELETAL Limbs - Upper limb brachymesomelia - Short, broad, radially bowed ulnae - Short radii - Lateral bowing proximal femur - Lateral bowing distal tibiae - Short, thin fibulae Hands - Single transverse palmar creases SKIN, NAILS, & HAIR Skin - Cutis marmorata ▲ Close
See 605552 for discussion of the phenotype associated with this quantitative trait locus (QTL). Mapping Kissebah et al. (2000) performed a genomewide scan by use of a 10-cM map in 2,209 individuals distributed over 507 nuclear Caucasian families. Pedigree-based analysis using a variance components linkage model demonstrated a QTL on chromosome 17p12 strongly linked to plasma leptin levels (lod = 5.0). This QTL has possible epistatic interaction with another QTL on chromosome 3q27 (605552) that is strongly linked to 6 traits (weight, waist circumference, leptin, insulin, insulin/glucose ratio, and hip circumference) associated with the phenotype (lod scores ranging from 2.4 to 3.5). Several candidate genes are located in both regions. INHERITANCE - Autosomal dominant GROWTH Weight - Abdominal obesity CARDIOVASCULAR Vascular - Hypertension LABORATORY ABNORMALITIES - Elevated fasting glucose levels ▲ Close
Van Bogaert (1953) and Hozay (1953) described a form of acroosteolysis with facial abnormalities in a brother and sister, aged 27 and 28, respectively. The parents were distantly related. The fingers and toes appeared infantile. The distal end of the ulna was underdeveloped. The facies were characterized by flat nasal bridge, thickened cheeks, deformed ears, micrognathia with abnormal dental position, and absent beard. Myopia and astigmatism were present. The male was mildly retarded; the female had done well in school. Ludo van Bogaert (1897-1989) lived and worked all his life in Antwerp, Belgium.
Posterior column ataxia - retinitis pigmentosa is characterized by the association of progressive sensory ataxia and retinitis pigmentosa. Epidemiology Around 20 cases have been described in the last 50 years. Clinical description Onset of symptoms usually occurs in childhood. The clinical picture is progressive, homogenous and includes severe sensory ataxia, proprioceptive loss (affecting the iliac crest, upper limbs and thorax), generalized areflexia and diffuse pigmentary retinopathy leading to blindness. Scoliosis, camptodactyly, achalasia and/or gastrointestinal motility dysfunction may also be present. Etiology The disease is associated with degeneration of the posterior column of the spinal cord.
A number sign (#) is used with this entry because posterior column ataxia with retinitis pigmentosa (AXPC1) is caused by homozygous mutation in the FLVCR1 gene (609144) on chromosome 1q32. Description Posterior column ataxia with retinitis pigmentosa is an autosomal recessive neurologic disorder characterized by childhood-onset retinitis pigmentosa and later onset of gait ataxia due to sensory loss (summary by Ishiura et al., 2011). Clinical Features Higgins et al. (1997) reported a large kindred in which 6 members had an autosomal recessive form of ataxia. Onset was in childhood with concentric contraction of the visual fields and proprioceptive loss. By the third decade, affected individuals became blind, had severe sensory ataxia, achalasia, scoliosis, and inanition (weakness and wasting).
Posterior column ataxia with retinitis pigmentosa (PCARP) is a genetic condition that affects vision and the nervous system. It is characterized by a loss of cells in the light sensitive tissue in the back of the eye ( retinitis pigmentosa ), abnormalities in the body's unconscious perception of movement and spatial orientation (proprioception), and muscle weakness and breakdown (atrophy). Other signs and symptoms may include curvature of the spine (scoliosis), an abnormal bending of the joints in the fingers (camptodactyly), and issues with the gastrointestinal system. PCARP is caused by mutations in the FLVCR1 gene and is inherited in an autosomal recessive manner. While there is no one treatment for this condition, there may be ways to manage the symptoms.
Statements consisting only of original research should be removed. ( October 2013 ) ( Learn how and when to remove this template message ) ( Learn how and when to remove this template message ) GEFS+ Specialty Neurology Generalized epilepsy with febrile seizures plus ( GEFS+ ) is a syndromic autosomal dominant disorder where afflicted individuals can exhibit numerous epilepsy phenotypes. [1] GEFS+ can persist beyond early childhood (i.e., 6 years of age). GEFS+ is also now believed to encompass three other epilepsy disorders: severe myoclonic epilepsy of infancy (SMEI), which is also known as Dravet's syndrome , borderline SMEI (SMEB), and intractable epilepsy of childhood (IEC). [2] [3] There are at least six types of GEFS+, delineated by their causative gene. ... The truncated mutant protein also seems to cause wild-type channels to inactivate at more hyperpolarized potentials, indicating that it also acts in a dominant negative manner. [39] Management [ edit ] Long term management is by use of anticonvulsant medication, principally valproate, stiripentol, topiramate or clobazam. [40] Ketogenic diet has also been found useful in certain cases [41] Management of breakthrough seizures is by benzodiazepine such as midazolam. [ citation needed ] See also [ edit ] Febrile seizures Idiopathic generalized epilepsy Dravet Syndrome Foundation International Dravet Epilepsy Action League References [ edit ] ^ a b Scheffer I, Berkovic S (1997). ... External links [ edit ] Classification D ICD - 10 : G40.3 OMIM : 604233 609800 607208 MeSH : C565809 v t e Diseases of ion channels Calcium channel Voltage-gated CACNA1A Familial hemiplegic migraine 1 Episodic ataxia 2 Spinocerebellar ataxia type-6 CACNA1C Timothy syndrome Brugada syndrome 3 Long QT syndrome 8 CACNA1F Ocular albinism 2 CSNB2A CACNA1S Hypokalemic periodic paralysis 1 Thyrotoxic periodic paralysis 1 CACNB2 Brugada syndrome 4 Ligand gated RYR1 Malignant hyperthermia Central core disease RYR2 CPVT1 ARVD2 Sodium channel Voltage-gated SCN1A Familial hemiplegic migraine 3 GEFS+ 2 Febrile seizure 3A SCN1B Brugada syndrome 6 GEFS+ 1 SCN4A Hypokalemic periodic paralysis 2 Hyperkalemic periodic paralysis Paramyotonia congenita Potassium-aggravated myotonia SCN4B Long QT syndrome 10 SCN5A Brugada syndrome 1 Long QT syndrome 3 SCN9A Erythromelalgia Febrile seizure 3B Paroxysmal extreme pain disorder Congenital insensitivity to pain Constitutively active SCNN1B / SCNN1G Liddle's syndrome SCNN1A / SCNN1B / SCNN1G Pseudohypoaldosteronism 1AR Potassium channel Voltage-gated KCNA1 Episodic ataxia 1 KCNA5 Familial atrial fibrillation 7 KCNC3 Spinocerebellar ataxia type-13 KCNE1 Jervell and Lange-Nielsen syndrome Long QT syndrome 5 KCNE2 Long QT syndrome 6 KCNE3 Brugada syndrome 5 KCNH2 Short QT syndrome KCNQ1 Jervell and Lange-Nielsen syndrome Romano–Ward syndrome Short QT syndrome Long QT syndrome 1 Familial atrial fibrillation 3 KCNQ2 BFNS1 Inward-rectifier KCNJ1 Bartter syndrome 2 KCNJ2 Andersen–Tawil syndrome Long QT syndrome 7 Short QT syndrome KCNJ11 TNDM3 KCNJ18 Thyrotoxic periodic paralysis 2 Chloride channel CFTR Cystic fibrosis Congenital absence of the vas deferens CLCN1 Thomsen disease Myotonia congenita CLCN5 Dent's disease CLCN7 Osteopetrosis A2, B4 BEST1 Vitelliform macular dystrophy CLCNKB Bartter syndrome 3 TRP channel TRPC6 FSGS2 TRPML1 Mucolipidosis type IV Connexin GJA1 Oculodentodigital dysplasia Hallermann–Streiff syndrome Hypoplastic left heart syndrome GJB1 Charcot–Marie–Tooth disease X1 GJB2 Keratitis–ichthyosis–deafness syndrome Ichthyosis hystrix Bart–Pumphrey syndrome Vohwinkel syndrome ) GJB3 / GJB4 Erythrokeratodermia variabilis Progressive symmetric erythrokeratodermia GJB6 Clouston's hidrotic ectodermal dysplasia Porin AQP2 Nephrogenic diabetes insipidus 2 See also: ion channels
Genetic lesions Attributable percent Examples Primary genetic testing method Aneuploidies 5-8% [15] Survivable autosomal trisomies (chromosomes 13 , 18 , 21 ), chromosome X monosomy (Turner syndrome) Karyotyping Copy number variants 10-12% [17] 22q11.2 deletion/duplication (velocardiofacial/DiGeorge syndrome) , 1 q21.1 deletion/duplication , 8p23.1 deletion/duplication , 15q11.2 deletion (Burnside-Butler syndrome) Array comparative genomic hybridization (also known as chromosomal microarray analysis) Inherited protein-coding single nucleotide variant (SNV) or small insertion/deletion (indel) 3-5% [18] Holt-Oram syndrome , Noonan syndrome , Alagille syndrome Gene panel De novo protein-coding SNV or indel ~10% [19] [16] Mutations in genes highly expressed during heart development Whole exome sequencing Molecular pathways [ edit ] The genes regulating the complex developmental sequence have only been partly elucidated. ... Notch1 is also associated with calcification of the aortic valve, the third most common cause of heart disease in adults. [24] [25] Mutations of a cell regulatory mechanism, the Ras / MAPK pathway are responsible for a variety of syndromes, including Noonan syndrome , LEOPARD syndrome , Costello syndrome and cardiofaciocutaneous syndrome in which there is cardiac involvement. [26] While the conditions listed are known genetic causes, there are likely many other genes which are more subtle. ... It is called hypoplastic left heart syndrome when it affects the left side of the heart and hypoplastic right heart syndrome when it affects the right side of the heart. ... "The RASopathies: developmental syndromes of Ras/MAPK pathway dysregulation" . ... Archived from the original on 2017-03-18. ^ "Hypoplastic Left Heart Syndrome" . American Heart. Archived from the original on 11 June 2010 .
Multiple endocrine neoplasia type 4 (MEN4) is a very rare form of MEN (see this term), an inherited cancer syndrome, characterized by parathyroid and anterior pituitary tumors, possibly associated with adrenal, renal, and reproductive organ tumors. Epidemiology The prevalence of multiple endocrine neoplasia type 4 is unknown, but the syndrome is very rare. To date, 12 index cases have been reported. ... Clinical description MEN4 is a recently described MEN-like syndrome similar to MEN1 (see this term). ... Cases of gastric and bronchial carcinoid tumor or Zollinger-Ellison syndrome (see this term) have also been reported.
Segregation studies in F1 and F2 crosses yielded frequencies of affected animals consistent with an autosomal recessive mode of inheritance. In rats with an MEN-like syndrome (Menx), with phenotypic overlap of MEN1 and MEN2A (171400), Pellegata et al. (2006) performed linkage analysis and identified a locus in a 4-Mb segment on rat chromosome 4, which includes the Cdkn1b gene.
Single cases were reported by Costanopoulos et al. (1975), Patrone et al. (1979), and Pinkerton et al. (1978). The syndrome is distinguished from neutrophil chemotactic deficiencies (162820) by the coexistence of defective random motility and peripheral blood neutropenia with normal bone marrow granulocyte reserve.
Clinical description 'This multiple congenital anomalies syndrome is characterized by dysmorphic features of the fetus and the newborn: the skull is misshapen, combining acrocephaly and cloverleaf deformity, fontanelles are very large; facial dysmorphism includes midface hypoplasia with telecanthus, short upturned nose, short philtrum, small inverted V-shaped mouth and low-set ears; limbs are also affected with bowed forearms, micromelia and acromicria with brachydactyly.' ... Recently, heterozygous mutations of the FAM111A gene, encoding a protein of unknown function and responsible of some autosomal dominant forms of Kenny-Caffey syndrome (see this term) with hypothyroidism and slender and dense bone, have been identified in patients with osteocraniostenosis. ... Differential diagnosis Differential diagnosis includes the hypo/akinesia sequence, Hallermann-Streiff-FranÁois syndrome, Kenny-Caffey syndrome and other slender bone dysplasias, and some cases of osteogenesis imperfecta with slender bones (see these terms).
Autosomal dominant Kenny-Caffey syndrome (KCS2; 127000) is also caused by mutation in the FAM11A gene. ... Verloes et al. (2005) described 2 brothers of Algerian ancestry with a distinctive disorder overlapping Melnick-Needles osteodysplasia (309350), Yunis-Varon syndrome (216340), and osteocraniostenosis that they suggested could represent a new syndrome. ... Elliott et al. (2006) noted some radiographic and histologic similarities to Hallermann-Streiff syndrome (HSS; 234100). The authors concluded that the term 'osteocraniostenosis' is an inaccurate term to describe this syndrome and suggested 'osteocraniosplenic syndrome' (see NOMENCLATURE below). ... Molecular Genetics In 5 patients with gracile bone dysplasia and 5 patients with autosomal dominant Kenny-Caffey syndrome (KCS2; 127000), Unger et al. (2013) identified heterozygosity for 6 mutations in the FAM111A gene (615292.0001-615292.0006, respectively). ... Spear (2006) concurred with Elliott et al. (2006), who suggested the term 'osteocraniosplenic syndrome.' INHERITANCE - Autosomal dominant GROWTH Height - Short stature Other - Failure to thrive, severe HEAD & NECK Face - Prominent forehead Eyes - Microphthalmia - Aniridia Mouth - Ankyloglossia CHEST Ribs Sternum Clavicles & Scapulae - Thin ribs and clavicles ABDOMEN - Ascites Spleen - Hypoplastic spleen - Asplenia (rare) GENITOURINARY External Genitalia (Male) - Micropenis SKELETAL - Bones dense but thin - Obliteration of medullary cavity seen on radiography Skull - Cloverleaf-shaped skull - Hypoplastic cranial bones - Decreased mineralization of skull (in some patients) Limbs - Micromelic short limbs - Flared metaphyses - Long bone fractures prenatally Hands - Brachydactyly NEUROLOGIC Central Nervous System - Hydrocephalus - Seizures - Developmental delay LABORATORY ABNORMALITIES - Hypocalcemia MISCELLANEOUS - Death in utero or in early infancy is common MOLECULAR BASIS - Caused by mutation in the family with sequence similarity 111, member A, gene (FAM111A, 615292.0002 ) ▲ Close
Osebold et al. (1998) described the findings and clinical course in a Caucasian woman, aged 23.5 years at the time of report, who had been followed since early childhood for a previously undescribed syndrome of painful osteocartilaginous metaplasia of long bone metaphyses and painful distal phalangeal osteolysis and soft tissue swelling.
Abnormally small chin Microgenia is the medical term for an unusually small or deformed chin . [1] The contrasting condition, an enlarged chin, is called "macrogenia". [2] [3] [4] Causes [ edit ] Can occur in anyone, but is often a sign of Down syndrome . [5] [6] [7] References [ edit ] ^ "microchinia - Definition from Merriam Webster's Medical Dictionary" . ... "Facial Plastic Surgery in Children with Down's Syndrome (preview page, with link to full content on plasreconsurg.com)" . ... Microchinia mentioned among other characteristics of Down's Syndrome about halfway down the page. ^ Meira Weiss (1994). ... Retrieved 2009-07-22 . v t e Congenital malformations and deformations of face and neck Face jaw : Otocephaly mouth : Macrostomia Microstomia lip : Macrocheilia Microcheilia chin : Microgenia multiple/other: Hallermann–Streiff syndrome Branchial cleft cyst Neck Webbed neck Ungrouped Preauricular sinus and cyst This medical sign article is a stub .
The deleted region is distal to that involved in the WAGR syndrome (194072). Mutation in the PAX6 gene can cause congenital eye malformations, including aniridia (AN; 106210). ... INHERITANCE - Autosomal dominant HEAD & NECK Eyes - Aniridia (in some patients) - Congenital eye malformations (in some patients) NEUROLOGIC Central Nervous System - Developmental delay - Intellectual disability - Speech and language delay Behavioral Psychiatric Manifestations - Autism MISCELLANEOUS - Incomplete penetrance - Contiguous gene deletion syndrome MOLECULAR BASIS - Susceptibility conferred by contiguous gene deletion (26-600kb) on chromosome 11p13 ▲ Close
Clinical Features Benit et al. (2004) reported a boy from Reunion Island with complex I deficiency and features of Leigh syndrome (see 256000) caused by mutations in the NDUFS3 gene. ... He gradually developed severe axial dystonia with oral and pharyngeal motor dysfunction, dysphagia, and a tetraparetic syndrome. At 10 years of age, mild elevation of CFS lactate was found. ... Haack et al. (2012) reported a patient with encephalopathy, myopathy, developmental delay, and lactic acidosis; Leigh syndrome was not noted. Molecular Genetics In a patient with complex I deficiency and features of Leigh syndrome, Benit et al. (2004) identified compound heterozygosity for mutations in the NDUFS3 gene (T145I, 603846.0001 and R199W, 603846.0002). ... INHERITANCE - Autosomal recessive HEAD & NECK Eyes - Pallor of the optic discs (patient A) RESPIRATORY - Respiratory insufficiency (patient A) ABDOMEN Pancreas - Pancreatitis (patient A) Gastrointestinal - Dysphagia (patient A) SKELETAL Spine - Kyphoscoliosis (patient A) MUSCLE, SOFT TISSUES - Hypotonia NEUROLOGIC Central Nervous System - Motor deterioration in the first decade (patient A) - Encephalopathy (patient B) - Dystonia (patient A) - Tetraparesis (patient A) - White matter abnormalities consistent with Leigh syndrome (patient A) METABOLIC FEATURES - Lactic acidosis LABORATORY ABNORMALITIES - Increased serum lactate - Mitochondrial respiratory complex I deficiency in various tissues MISCELLANEOUS - Two unrelated patients with different phenotypes have been reported (last curated January 2019) - Patient A had onset of neurologic and multisystemic deterioration at age 9 years, resulting in death in the second decade - Patient B had onset before age 3 years MOLECULAR BASIS - Caused by mutation in the NADH-ubiquinone oxidoreductase core subunit S3 gene (NDUFS3, 603846.0001 ) ▲ Close
A number sign (#) is used with this entry because of evidence that mitochondrial complex I deficiency nuclear type 9 (MC1DN9) is caused by homozygous mutation in the NDUFS6 gene (603848) on chromosome 5p15. For a discussion of genetic heterogeneity of mitochondrial complex I deficiency, see 252010. Clinical Features Kirby et al. (2004) reported 2 unrelated patients with complex I deficiency. Both patients had lethal infantile mitochondrial disease with death within the first 2 weeks of life. Spiegel et al. (2009) reported 2 unrelated infants, both of Jewish Caucasus descent, with fatal infantile lactic acidosis resulting from severe complex I deficiency.
Cranial CT scans showed brain atrophy, but cranial MRIs were not available to confirm Leigh syndrome. Lactate and pyruvate concentrations in blood and cerebrospinal fluid were elevated.
A number sign (#) is used with this entry because of evidence that mitochondrial complex I deficiency nuclear type 25 (MC1DN25) is caused by homozygous or compound heterozygous mutation in the NDUFB3 gene (603839) on chromosome 2q33. For a discussion of genetic heterogeneity of mitochondrial complex I deficiency, see 252010. Clinical Features Calvo et al. (2012) reported a female infant, born of unrelated parents of British and Dutch descent, with severe lethal mitochondrial complex I deficiency. The pregnancy was complicated by intrauterine growth retardation and premature birth at 31 weeks' gestation; respiratory insufficiency required extensive artificial ventilation in the neonatal period. After discharge home, she showed hypotonia with poor feeding and significant lactic acidosis and died unexpectedly at age 4 months.
Some people with mitochondrial complex I deficiency have groups of signs and symptoms that are classified as a specific syndrome. For example, a condition called Leigh syndrome is most commonly caused by mitochondrial complex I deficiency. Leigh syndrome is characterized by progressive loss of mental and movement abilities (developmental or psychomotor regression) and typically results in death within 2 to 3 years from the onset of symptoms. Another condition that can be caused by mitochondrial complex I deficiency, Leber hereditary optic neuropathy, is associated mainly with vision problems due to optic nerve degeneration. These syndromes can also have other causes. Frequency Mitochondrial diseases are thought to occur in about 1 in 8,500 people.
Gerards et al. (2010) reported 2 adult sibs, born of consanguineous Moroccan parents, who developed symptoms of complex I deficiency with Leigh syndrome (see 256000) in early childhood. ... Saada et al. (2012) reported 5 children from 2 unrelated families of Ashkenazi Jewish origin with Leigh syndrome associated with deficiencies of mitochondrial complexes I and IV. ... In 2 adult sibs, born of consanguineous Moroccan parents, who developed symptoms of complex I deficiency with Leigh syndrome in early childhood, Gerards et al. (2010) identified a homozygous mutation in the NDUFAF5 gene (L159F; 612360.0002). ... In 5 children from 2 unrelated families of Ashkenazi Jewish origin with Leigh syndrome associated with deficiencies of mitochondrial complexes I and IV, Saada et al. (2012) identified a homozygous c.749G-T transversion in exon 7 of the NDUFAF5 gene, resulting in a gly250-to-val (G250V) substitution at a conserved residue. ... INHERITANCE - Autosomal recessive GROWTH Other - Intrauterine growth restriction (IUGR) - Failure to thrive HEAD & NECK Eyes - Nystagmus - Ptosis - Optic atrophy (in some patients) ABDOMEN Gastrointestinal - Feeding difficulties MUSCLE, SOFT TISSUES - Hypotonia NEUROLOGIC Central Nervous System - Global developmental delay - Impaired intellectual development - Neurologic regression - Spasticity - Extrapyramidal signs - Choreoathetosis - Dystonic movements - Dysarthria - Seizures (in some patients) - Signal abnormalities consistent with Leigh syndrome seen on brain imaging - Agenesis of the corpus callosum (in some patients) METABOLIC FEATURES - Lactic acidosis LABORATORY ABNORMALITIES - Increased lactate in serum and CSF - Mitochondrial respiratory complex I deficiency in various tissues MISCELLANEOUS - Onset in infancy or childhood - Early death may occur - Highly variable phenotype and severity MOLECULAR BASIS - Caused by mutation in the NADH-ubiquinone oxidoreductase complex assembly factor 5 gene (NDUFAF5, 612360.0001 ) ▲ Close
Cranial MRI showed hyperintense signals resembling those found in Leigh syndrome (see 256000). Cardiac ultrasound showed concentric hypertrophy of the left ventricle with hypercontractility. ... Clinical phenotypes included Leigh syndrome in 7 patients, Leigh-like syndrome in 6, fatal infantile lactic acidosis in 3, neonatal cardiomyopathy with lactic acidosis in 3, macrocephaly with progressive leukodystrophy in 2, and a residual group of unspecified encephalomyopathy in 6, subdivided into progressive (in 4) and stable (in 2) variants. ... In a patient with complex I deficiency resulting in Leigh syndrome, Petruzzella et al. (2001) identified a homozygous nonsense mutation in the NDUFS4 cDNA (W15X; 602694.0004). ... In 2 sisters in a consanguineous family with complex I deficiency and Leigh syndrome, Benit et al. (2003) identified a homozygous splice site mutation in the NDUFS4 locus (602694.0005). ... Genotype/Phenotype Correlations Mutations in the nuclear-encoded genes NDUFS1, NDUFS4, NDUFS7, NDUFS8, and NDUFV1 result in neurologic diseases, mostly Leigh syndrome or Leigh-like syndrome. Mutations in NDUFS2 and NDUFV2 have been associated with hypertrophic cardiomyopathy and encephalomyopathy.
A number sign (#) is used with this entry because of evidence that mitochondrial complex I deficiency nuclear type 18 (MC1DN18) is caused by homozygous or compound heterozygous mutation in the NDUFAF3 gene (612911) on chromosome 3p21. For a discussion of genetic heterogeneity of mitochondrial complex I deficiency, see 252010. Clinical Features Saada et al. (2009) reported 5 patients from 3 families with severe complex I deficiency. All patients died by age 6 months. Three sibs in the first family presented similarly with severe lactic acidosis. In a second family, the infant was hypoactive, sucked poorly, had macrocephaly, a weak cry, wide anterior fontanel, and axial hypotonia.
Martin et al. (2005) reported a Spanish child with complex I deficiency and features of Leigh syndrome (see 256000) with mutation in the NDUFS1 gene. ... Martin et al. (2005) reported a Spanish child with complex I deficiency and features of Leigh syndrome caused by a homozygous mutation in the NDUFS1 gene (L231V; 157655.0004). ... INHERITANCE - Autosomal recessive GROWTH Other - Failure to thrive HEAD & NECK Head - Microcephaly, progressive (in some patients) Eyes - Optic atrophy - Nystagmus - Ptosis - Strabismus - Ophthalmoplegia RESPIRATORY - Respiratory insufficiency - Apnea ABDOMEN - Dysphagia - Vomiting MUSCLE, SOFT TISSUES - Hypotonia NEUROLOGIC Central Nervous System - Global developmental delay - Developmental regression - Impaired intellectual development - Poor speech - Ataxia - Seizures (in some patients) - Lethargy - Irritability - Pyramidal syndrome - Hyperreflexia - Extensor plantar responses - Dystonia - Leukodystrophy - Leukoencephalopathy - White matter abnormalities consistent with Leigh syndrome seen on brain imaging - Cerebellar atrophy - Brain atrophy - Brainstem abnormalities - Cystic brain lesions METABOLIC FEATURES - Lactic acidosis LABORATORY ABNORMALITIES - Increased serum and CSF lactate - Mitochondrial respiratory complex I deficiency in various tissues MISCELLANEOUS - Onset in infancy - Symptoms may be exacerbated by concurrent infection - Episodic deterioration - Progressive disorder - Variable phenotype - Early death may occur MOLECULAR BASIS - Caused by mutation in the NADH-ubiquinone oxidoreductase core subunit S1 gene (NDUFS1, 157655.0001 ) ▲ Close
A number sign (#) is used with this entry because of evidence that mitochondrial complex I deficiency nuclear type 24 (MC1DN24) is caused by homozygous mutation in the NDUFB9 gene (601445) on chromosome 8q24. One such family has been reported. For a discussion of genetic heterogeneity of mitochondrial complex I deficiency, see 252010. Clinical Features Haack et al. (2012) reported 2 brothers with mitochondrial complex I deficiency. The proband had onset in infancy of progressive hypotonia associated with increased serum lactate. Molecular Genetics In 2 brothers with mitochondrial complex I deficiency, Haack et al. (2012) identified a homozygous missense mutation in the NDUFB9 gene (L64P; 601445.0001).
Features may include macrocephaly (large head) with progressive leukodystrophy , encephalopathy, hypertrophic cardiomyopathy , myopathy , liver disease, Leigh syndrome , Leber hereditary optic neuropathy , and some forms of Parkinson disease .