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Intellectual developmental disorder with severe speech and ambulation defects(IDDSSAD)

MedGen UID:
1682234
Concept ID:
C5193115
Disease or Syndrome
Synonyms: IDDSSAD; INTELLECTUAL DEVELOPMENTAL DISORDER WITH SEVERE SPEECH AND AMBULATION DEFECTS
 
Gene (location): ACTL6B (7q22.1)
 
Monarch Initiative: MONDO:0032770
OMIM®: 618470

Definition

Intellectual developmental disorder with severe speech and ambulation defects (IDDSSAD) is an autosomal dominant neurodevelopmental disorder with onset of features in infancy or early childhood. Affected individuals have global developmental delay with impaired intellectual development and absent speech, and most cannot walk independently. Common dysmorphic features include prominent forehead and wide mouth (summary by Bell et al., 2019). [from OMIM]

Clinical features

From HPO
Short distal phalanx of finger
MedGen UID:
326590
Concept ID:
C1839829
Finding
Short distance from the end of the finger to the most distal interphalangeal crease or the distal interphalangeal joint flexion point. That is, hypoplasia of one or more of the distal phalanx of finger.
Intellectual disability, severe
MedGen UID:
48638
Concept ID:
C0036857
Mental or Behavioral Dysfunction
Severe mental retardation is defined as an intelligence quotient (IQ) in the range of 20-34.
Global brain atrophy
MedGen UID:
66840
Concept ID:
C0241816
Pathologic Function
Unlocalized atrophy of the brain with decreased total brain matter volume and increased ventricular size.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Bilateral tonic-clonic seizure
MedGen UID:
141670
Concept ID:
C0494475
Sign or Symptom
A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase.
Inability to walk
MedGen UID:
107860
Concept ID:
C0560046
Finding
Incapability to ambulate.
Broad-based gait
MedGen UID:
167799
Concept ID:
C0856863
Finding
An abnormal gait pattern in which persons stand and walk with their feet spaced widely apart. This is often a component of cerebellar ataxia.
Autistic behavior
MedGen UID:
163547
Concept ID:
C0856975
Mental or Behavioral Dysfunction
Persistent deficits in social interaction and communication and interaction as well as a markedly restricted repertoire of activity and interest as well as repetitive patterns of behavior.
Severe global developmental delay
MedGen UID:
332436
Concept ID:
C1837397
Finding
A severe delay in the achievement of motor or mental milestones in the domains of development of a child.
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
Infantile spasms
MedGen UID:
854616
Concept ID:
C3887898
Disease or Syndrome
Infantile spasms represent a subset of "epileptic spasms". Infantile Spasms are epileptic spasms starting in the first year of life (infancy).
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Diastema
MedGen UID:
3800
Concept ID:
C0011998
Finding
Increased space between two adjacent teeth in the same dental arch.
Wide mouth
MedGen UID:
44238
Concept ID:
C0024433
Congenital Abnormality
Distance between the oral commissures more than 2 SD above the mean. Alternatively, an apparently increased width of the oral aperture (subjective).
Bulbous nose
MedGen UID:
66013
Concept ID:
C0240543
Finding
Increased volume and globular shape of the anteroinferior aspect of the nose.
Prominent forehead
MedGen UID:
373291
Concept ID:
C1837260
Finding
Forward prominence of the entire forehead, due to protrusion of the frontal bone.
Broad forehead
MedGen UID:
338610
Concept ID:
C1849089
Finding
Width of the forehead or distance between the frontotemporales is more than two standard deviations above the mean (objective); or apparently increased distance between the two sides of the forehead.
Small nail
MedGen UID:
537942
Concept ID:
C0263523
Finding
A nail that is diminished in length and width, i.e., underdeveloped nail.
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).

Recent clinical studies

Etiology

Ebrahimi-Fakhari D, Teinert J, Behne R, Wimmer M, D'Amore A, Eberhardt K, Brechmann B, Ziegler M, Jensen DM, Nagabhyrava P, Geisel G, Carmody E, Shamshad U, Dies KA, Yuskaitis CJ, Salussolia CL, Ebrahimi-Fakhari D, Pearson TS, Saffari A, Ziegler A, Kölker S, Volkmann J, Wiesener A, Bearden DR, Lakhani S, Segal D, Udwadia-Hegde A, Martinuzzi A, Hirst J, Perlman S, Takiyama Y, Xiromerisiou G, Vill K, Walker WO, Shukla A, Dubey Gupta R, Dahl N, Aksoy A, Verhelst H, Delgado MR, Kremlikova Pourova R, Sadek AA, Elkhateeb NM, Blumkin L, Brea-Fernández AJ, Dacruz-Álvarez D, Smol T, Ghoumid J, Miguel D, Heine C, Schlump JU, Langen H, Baets J, Bulk S, Darvish H, Bakhtiari S, Kruer MC, Lim-Melia E, Aydinli N, Alanay Y, El-Rashidy O, Nampoothiri S, Patel C, Beetz C, Bauer P, Yoon G, Guillot M, Miller SP, Bourinaris T, Houlden H, Robelin L, Anheim M, Alamri AS, Mahmoud AAH, Inaloo S, Habibzadeh P, Faghihi MA, Jansen AC, Brock S, Roubertie A, Darras BT, Agrawal PB, Santorelli FM, Gleeson J, Zaki MS, Sheikh SI, Bennett JT, Sahin M
Brain 2020 Oct 1;143(10):2929-2944. doi: 10.1093/brain/awz307. PMID: 32979048Free PMC Article
Saikusa T, Kawaguchi M, Tanioka Tetsu T T, Nabatame Shin N S, Takahashi S, Yuge K, Nagamitsu SI, Takahashi T, Yamashita Y, Kobayashi Y, Hirayama C, Kakuma T, Matsuishi T, Itoh M
Brain Dev 2020 Nov;42(10):705-712. Epub 2020 Jul 17 doi: 10.1016/j.braindev.2020.06.012. PMID: 32684376
Seltzer LE, Ma M, Ahmed S, Bertrand M, Dobyns WB, Wheless J, Paciorkowski AR
Epilepsia 2014 Aug;55(8):1292-300. Epub 2014 May 16 doi: 10.1111/epi.12648. PMID: 24836831Free PMC Article
Stoll C
Clin Dysmorphol 2002 Jan;11(1):1-7. doi: 10.1097/00019605-200201000-00001. PMID: 11822698
Evenhuis HM
Arch Neurol 1990 Mar;47(3):263-7. doi: 10.1001/archneur.1990.00530030029011. PMID: 2138013

Diagnosis

Cooley Coleman JA, Sarasua SM, Boccuto L, Moore HW, Skinner SA, DeLuca JM
Am J Med Genet A 2021 Dec;185(12):3884-3894. Epub 2021 Jun 29 doi: 10.1002/ajmg.a.62412. PMID: 34184825
Ebrahimi-Fakhari D, Teinert J, Behne R, Wimmer M, D'Amore A, Eberhardt K, Brechmann B, Ziegler M, Jensen DM, Nagabhyrava P, Geisel G, Carmody E, Shamshad U, Dies KA, Yuskaitis CJ, Salussolia CL, Ebrahimi-Fakhari D, Pearson TS, Saffari A, Ziegler A, Kölker S, Volkmann J, Wiesener A, Bearden DR, Lakhani S, Segal D, Udwadia-Hegde A, Martinuzzi A, Hirst J, Perlman S, Takiyama Y, Xiromerisiou G, Vill K, Walker WO, Shukla A, Dubey Gupta R, Dahl N, Aksoy A, Verhelst H, Delgado MR, Kremlikova Pourova R, Sadek AA, Elkhateeb NM, Blumkin L, Brea-Fernández AJ, Dacruz-Álvarez D, Smol T, Ghoumid J, Miguel D, Heine C, Schlump JU, Langen H, Baets J, Bulk S, Darvish H, Bakhtiari S, Kruer MC, Lim-Melia E, Aydinli N, Alanay Y, El-Rashidy O, Nampoothiri S, Patel C, Beetz C, Bauer P, Yoon G, Guillot M, Miller SP, Bourinaris T, Houlden H, Robelin L, Anheim M, Alamri AS, Mahmoud AAH, Inaloo S, Habibzadeh P, Faghihi MA, Jansen AC, Brock S, Roubertie A, Darras BT, Agrawal PB, Santorelli FM, Gleeson J, Zaki MS, Sheikh SI, Bennett JT, Sahin M
Brain 2020 Oct 1;143(10):2929-2944. doi: 10.1093/brain/awz307. PMID: 32979048Free PMC Article
Vera G, Sorlin A, Delplancq G, Lecoquierre F, Brasseur-Daudruy M, Petit F, Smol T, Ziegler A, Bonneau D, Colin E, Mercier S, Cogné B, Bézieau S, Edery P, Lesca G, Chatron N, Sabatier I, Duban-Bedu B, Colson C, Piton A, Durand B, Capri Y, Perrin L, Wiesener A, Zweier C, Maroofian R, Carroll CJ, Galehdari H, Mazaheri N, Callewaert B, Giulianno F, Zaafrane-Khachnaoui K, Buchert-Lo R, Haack T, Magg J, Rieß A, Blandfort M, Waldmüller S, Horber V, Leonardi E, Polli R, Turolla L, Murgia A, Frebourg T, Lebre AS, Nicolas G, Saugier-Veber P, Guerrot AM
Eur J Med Genet 2020 Oct;63(10):104004. Epub 2020 Jul 17 doi: 10.1016/j.ejmg.2020.104004. PMID: 32688057
Seltzer LE, Ma M, Ahmed S, Bertrand M, Dobyns WB, Wheless J, Paciorkowski AR
Epilepsia 2014 Aug;55(8):1292-300. Epub 2014 May 16 doi: 10.1111/epi.12648. PMID: 24836831Free PMC Article
Evenhuis HM
Arch Neurol 1990 Mar;47(3):263-7. doi: 10.1001/archneur.1990.00530030029011. PMID: 2138013

Prognosis

Saikusa T, Kawaguchi M, Tanioka Tetsu T T, Nabatame Shin N S, Takahashi S, Yuge K, Nagamitsu SI, Takahashi T, Yamashita Y, Kobayashi Y, Hirayama C, Kakuma T, Matsuishi T, Itoh M
Brain Dev 2020 Nov;42(10):705-712. Epub 2020 Jul 17 doi: 10.1016/j.braindev.2020.06.012. PMID: 32684376
Seltzer LE, Ma M, Ahmed S, Bertrand M, Dobyns WB, Wheless J, Paciorkowski AR
Epilepsia 2014 Aug;55(8):1292-300. Epub 2014 May 16 doi: 10.1111/epi.12648. PMID: 24836831Free PMC Article
Stoll C
Clin Dysmorphol 2002 Jan;11(1):1-7. doi: 10.1097/00019605-200201000-00001. PMID: 11822698

Clinical prediction guides

Saikusa T, Kawaguchi M, Tanioka Tetsu T T, Nabatame Shin N S, Takahashi S, Yuge K, Nagamitsu SI, Takahashi T, Yamashita Y, Kobayashi Y, Hirayama C, Kakuma T, Matsuishi T, Itoh M
Brain Dev 2020 Nov;42(10):705-712. Epub 2020 Jul 17 doi: 10.1016/j.braindev.2020.06.012. PMID: 32684376
Evenhuis HM
Arch Neurol 1990 Mar;47(3):263-7. doi: 10.1001/archneur.1990.00530030029011. PMID: 2138013

Recent systematic reviews

Cooley Coleman JA, Sarasua SM, Boccuto L, Moore HW, Skinner SA, DeLuca JM
Am J Med Genet A 2021 Dec;185(12):3884-3894. Epub 2021 Jun 29 doi: 10.1002/ajmg.a.62412. PMID: 34184825

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