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Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia(NEDIDHA)

MedGen UID:
1648291
Concept ID:
C4749014
Disease or Syndrome
Synonyms: NEDIDHA; NEURODEVELOPMENTAL DISORDER WITH IMPAIRED INTELLECTUAL DEVELOPMENT, HYPOTONIA, AND ATAXIA
 
Gene (location): DOCK3 (3p21.2)
 
Monarch Initiative: MONDO:0032661
OMIM®: 618292

Clinical features

From HPO
Tapered finger
MedGen UID:
98098
Concept ID:
C0426886
Finding
The gradual reduction in girth of the finger from proximal to distal.
Long fingers
MedGen UID:
346836
Concept ID:
C1858091
Finding
The middle finger is more than 2 SD above the mean for newborns 27 to 41 weeks EGA or above the 97th centile for children from birth to 16 years of age AND the five digits retain their normal length proportions relative to each other (i.e., it is not the case that the middle finger is the only lengthened digit), or, Fingers that appear disproportionately long compared to the palm of the hand.
Mild short stature
MedGen UID:
461427
Concept ID:
C3150077
Finding
A mild degree of short stature, more than -2 SD but not more than -3 SD from mean corrected for age and sex.
Unsteady gait
MedGen UID:
68544
Concept ID:
C0231686
Finding
A shaky or wobbly manner of walking.
Delayed ability to walk
MedGen UID:
66034
Concept ID:
C0241726
Finding
A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Gait ataxia
MedGen UID:
155642
Concept ID:
C0751837
Sign or Symptom
A type of ataxia characterized by the impairment of the ability to coordinate the movements required for normal walking. Gait ataxia is characteirzed by a wide-based staggering gait with a tendency to fall.
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
Reduced tendon reflexes
MedGen UID:
356648
Concept ID:
C1866934
Finding
Diminution of tendon reflexes, which is an invariable sign of peripheral nerve disease.
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.
Relative macrocephaly
MedGen UID:
338607
Concept ID:
C1849075
Congenital Abnormality
A relatively mild degree of macrocephaly in which the head circumference is not above two standard deviations from the mean, but appears dysproportionately large when other factors such as body stature are taken into account.
Dental malocclusion
MedGen UID:
9869
Concept ID:
C0024636
Anatomical Abnormality
Dental malocclusion refers to an abnormality of the occlusion, or alignment, of the teeth and the way the upper and lower teeth fit together, resulting in overcrowding of teeth or in abnormal bite patterns.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Mandibular prognathia
MedGen UID:
98316
Concept ID:
C0399526
Finding
Abnormal prominence of the chin related to increased length of the mandible.
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.
Epicanthus
MedGen UID:
151862
Concept ID:
C0678230
Congenital Abnormality
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).
Long face
MedGen UID:
324419
Concept ID:
C1836047
Finding
Facial height (length) is more than 2 standard deviations above the mean (objective); or, an apparent increase in the height (length) of the face (subjective).
Anteverted nares
MedGen UID:
326648
Concept ID:
C1840077
Finding
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
Pointed chin
MedGen UID:
336193
Concept ID:
C1844505
Finding
A marked tapering of the lower face to the chin.

Recent clinical studies

Etiology

Sidpra J, Sudhakar S, Biswas A, Massey F, Turchetti V, Lau T, Cook E, Alvi JR, Elbendary HM, Jewell JL, Riva A, Orsini A, Vignoli A, Federico Z, Rosenblum J, Schoonjans AS, de Wachter M, Delgado Alvarez I, Felipe-Rucián A, Haridy NA, Haider S, Zaman M, Banu S, Anwaar N, Rahman F, Maqbool S, Yadav R, Salpietro V, Maroofian R, Patel R, Radhakrishnan R, Prabhu SP, Lichtenbelt K, Stewart H, Murakami Y, Löbel U, D'Arco F, Wakeling E, Jones W, Hay E, Bhate S, Jacques TS, Mirsky DM, Whitehead MT, Zaki MS, Sultan T, Striano P, Jansen AC, Lequin M, de Vries LS, Severino M, Edmondson AC, Menzies L, Campeau PM, Houlden H, McTague A, Efthymiou S, Mankad K
Brain 2024 Aug 1;147(8):2775-2790. doi: 10.1093/brain/awae056. PMID: 38456468Free PMC Article
Lee HHC, McGinty GE, Pearl PL, Rotenberg A
Int J Mol Sci 2022 Feb 26;23(5) doi: 10.3390/ijms23052606. PMID: 35269750Free PMC Article
Bretón Martínez JR, Cánovas Martínez A, Casaña Pérez S, Escribá Alepuz J, Giménez Vázquez F
J Inherit Metab Dis 2007 Oct;30(5):829. Epub 2007 Jun 21 doi: 10.1007/s10545-007-0618-7. PMID: 17578678

Diagnosis

Jacobs EZ, Brown K, Byler MC, D'haenens E, Dheedene A, Henderson LB, Humberson JB, van Jaarsveld RH, Kanani F, Lebel RR, Millan F, Oegema R, Oostra A, Parker MJ, Rhodes L, Saenz M, Seaver LH, Si Y, Vanlander A, Vergult S, Callewaert B
Clin Genet 2021 Feb;99(2):259-268. Epub 2020 Nov 23 doi: 10.1111/cge.13874. PMID: 33131045
Smol T, Petit F, Piton A, Keren B, Sanlaville D, Afenjar A, Baker S, Bedoukian EC, Bhoj EJ, Bonneau D, Boudry-Labis E, Bouquillon S, Boute-Benejean O, Caumes R, Chatron N, Colson C, Coubes C, Coutton C, Devillard F, Dieux-Coeslier A, Doco-Fenzy M, Ewans LJ, Faivre L, Fassi E, Field M, Fournier C, Francannet C, Genevieve D, Giurgea I, Goldenberg A, Green AK, Guerrot AM, Heron D, Isidor B, Keena BA, Krock BL, Kuentz P, Lapi E, Le Meur N, Lesca G, Li D, Marey I, Mignot C, Nava C, Nesbitt A, Nicolas G, Roche-Lestienne C, Roscioli T, Satre V, Santani A, Stefanova M, Steinwall Larsen S, Saugier-Veber P, Picker-Minh S, Thuillier C, Verloes A, Vieville G, Wenzel M, Willems M, Whalen S, Zarate YA, Ziegler A, Manouvrier-Hanu S, Kalscheuer VM, Gerard B, Ghoumid J
Neurogenetics 2018 May;19(2):93-103. Epub 2018 Mar 6 doi: 10.1007/s10048-018-0541-0. PMID: 29511999
Helbig KL, Mroske C, Moorthy D, Sajan SA, Velinov M
Clin Genet 2017 Oct;92(4):430-433. Epub 2017 Mar 30 doi: 10.1111/cge.12995. PMID: 28195318
Bretón Martínez JR, Cánovas Martínez A, Casaña Pérez S, Escribá Alepuz J, Giménez Vázquez F
J Inherit Metab Dis 2007 Oct;30(5):829. Epub 2007 Jun 21 doi: 10.1007/s10545-007-0618-7. PMID: 17578678
Borgatti R, Piccinelli P, Passoni D, Dalprà L, Miozzo M, Micheli R, Gagliardi C, Balottin U
Pediatr Neurol 2001 Feb;24(2):111-6. doi: 10.1016/s0887-8994(00)00244-7. PMID: 11275459

Therapy

Johannesen KM, Gardella E, Encinas AC, Lehesjoki AE, Linnankivi T, Petersen MB, Lund ICB, Blichfeldt S, Miranda MJ, Pal DK, Lascelles K, Procopis P, Orsini A, Bonuccelli A, Giacomini T, Helbig I, Fenger CD, Sisodiya SM, Hernandez-Hernandez L, Krithika S, Rumple M, Masnada S, Valente M, Cereda C, Giordano L, Accorsi P, Bürki SE, Mancardi M, Korff C, Guerrini R, von Spiczak S, Hoffman-Zacharska D, Mazurczak T, Coppola A, Buono S, Vecchi M, Hammer MF, Varesio C, Veggiotti P, Lal D, Brünger T, Zara F, Striano P, Rubboli G, Møller RS
Epilepsia 2019 May;60(5):830-844. Epub 2019 Apr 10 doi: 10.1111/epi.14705. PMID: 30968951
de Brouwer AP, Williams KL, Duley JA, van Kuilenburg AB, Nabuurs SB, Egmont-Petersen M, Lugtenberg D, Zoetekouw L, Banning MJ, Roeffen M, Hamel BC, Weaving L, Ouvrier RA, Donald JA, Wevers RA, Christodoulou J, van Bokhoven H
Am J Hum Genet 2007 Sep;81(3):507-18. Epub 2007 Aug 3 doi: 10.1086/520706. PMID: 17701896Free PMC Article

Prognosis

Sidpra J, Sudhakar S, Biswas A, Massey F, Turchetti V, Lau T, Cook E, Alvi JR, Elbendary HM, Jewell JL, Riva A, Orsini A, Vignoli A, Federico Z, Rosenblum J, Schoonjans AS, de Wachter M, Delgado Alvarez I, Felipe-Rucián A, Haridy NA, Haider S, Zaman M, Banu S, Anwaar N, Rahman F, Maqbool S, Yadav R, Salpietro V, Maroofian R, Patel R, Radhakrishnan R, Prabhu SP, Lichtenbelt K, Stewart H, Murakami Y, Löbel U, D'Arco F, Wakeling E, Jones W, Hay E, Bhate S, Jacques TS, Mirsky DM, Whitehead MT, Zaki MS, Sultan T, Striano P, Jansen AC, Lequin M, de Vries LS, Severino M, Edmondson AC, Menzies L, Campeau PM, Houlden H, McTague A, Efthymiou S, Mankad K
Brain 2024 Aug 1;147(8):2775-2790. doi: 10.1093/brain/awae056. PMID: 38456468Free PMC Article
Yıldız Bölükbaşı E, Afzal M, Mumtaz S, Ahmad N, Malik S, Tolun A
Am J Med Genet A 2017 Sep;173(9):2494-2499. Epub 2017 Jun 21 doi: 10.1002/ajmg.a.38332. PMID: 28636205

Clinical prediction guides

Sidpra J, Sudhakar S, Biswas A, Massey F, Turchetti V, Lau T, Cook E, Alvi JR, Elbendary HM, Jewell JL, Riva A, Orsini A, Vignoli A, Federico Z, Rosenblum J, Schoonjans AS, de Wachter M, Delgado Alvarez I, Felipe-Rucián A, Haridy NA, Haider S, Zaman M, Banu S, Anwaar N, Rahman F, Maqbool S, Yadav R, Salpietro V, Maroofian R, Patel R, Radhakrishnan R, Prabhu SP, Lichtenbelt K, Stewart H, Murakami Y, Löbel U, D'Arco F, Wakeling E, Jones W, Hay E, Bhate S, Jacques TS, Mirsky DM, Whitehead MT, Zaki MS, Sultan T, Striano P, Jansen AC, Lequin M, de Vries LS, Severino M, Edmondson AC, Menzies L, Campeau PM, Houlden H, McTague A, Efthymiou S, Mankad K
Brain 2024 Aug 1;147(8):2775-2790. doi: 10.1093/brain/awae056. PMID: 38456468Free PMC Article
Petkova SP, Adhikari A, Berg EL, Fenton TA, Duis J, Silverman JL
Autism Res 2022 May;15(5):821-833. Epub 2022 Mar 10 doi: 10.1002/aur.2697. PMID: 35274462Free PMC Article
Jacobs EZ, Brown K, Byler MC, D'haenens E, Dheedene A, Henderson LB, Humberson JB, van Jaarsveld RH, Kanani F, Lebel RR, Millan F, Oegema R, Oostra A, Parker MJ, Rhodes L, Saenz M, Seaver LH, Si Y, Vanlander A, Vergult S, Callewaert B
Clin Genet 2021 Feb;99(2):259-268. Epub 2020 Nov 23 doi: 10.1111/cge.13874. PMID: 33131045
Johannesen KM, Gardella E, Encinas AC, Lehesjoki AE, Linnankivi T, Petersen MB, Lund ICB, Blichfeldt S, Miranda MJ, Pal DK, Lascelles K, Procopis P, Orsini A, Bonuccelli A, Giacomini T, Helbig I, Fenger CD, Sisodiya SM, Hernandez-Hernandez L, Krithika S, Rumple M, Masnada S, Valente M, Cereda C, Giordano L, Accorsi P, Bürki SE, Mancardi M, Korff C, Guerrini R, von Spiczak S, Hoffman-Zacharska D, Mazurczak T, Coppola A, Buono S, Vecchi M, Hammer MF, Varesio C, Veggiotti P, Lal D, Brünger T, Zara F, Striano P, Rubboli G, Møller RS
Epilepsia 2019 May;60(5):830-844. Epub 2019 Apr 10 doi: 10.1111/epi.14705. PMID: 30968951
Borgatti R, Piccinelli P, Passoni D, Dalprà L, Miozzo M, Micheli R, Gagliardi C, Balottin U
Pediatr Neurol 2001 Feb;24(2):111-6. doi: 10.1016/s0887-8994(00)00244-7. PMID: 11275459

Recent systematic reviews

Jacobs EZ, Brown K, Byler MC, D'haenens E, Dheedene A, Henderson LB, Humberson JB, van Jaarsveld RH, Kanani F, Lebel RR, Millan F, Oegema R, Oostra A, Parker MJ, Rhodes L, Saenz M, Seaver LH, Si Y, Vanlander A, Vergult S, Callewaert B
Clin Genet 2021 Feb;99(2):259-268. Epub 2020 Nov 23 doi: 10.1111/cge.13874. PMID: 33131045

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